Clincosm LogoSign in Get a demo

Reduced Opioid Analgesic Requirements Via Improved Endogenous Opioid Function

Sponsor
Vanderbilt University Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT02469077
Collaborator
National Institute on Drug Abuse (NIDA) (NIH)
117
Enrollment
2
Locations
2
Arms
49
Duration (Months)
58.5
Patients Per Site
1.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Chronic Pain (CP) management has increasingly utilized long-term opioid analgesic therapy, a change associated with increased opioid abuse (via greater exposure in vulnerable individuals), non-pain health consequences (hormone changes, falls), and a dramatic rise in opioid-related overdoses and deaths. Treatment strategies that minimize the need for chronic high-dose opioids are sorely needed. This project will test the novel hypothesis that effective pain relief can be achieved at lower opioid analgesic doses by increasing levels of endogenous opioids (EOs).

Condition or Disease Intervention/Treatment Phase
N/A

Detailed Description

There are three separate goals of the study: 1) test the effects of the intervention (versus control) on clinical outcomes, 2) test for endogenous opioid mechanisms of the intervention (indexed by the difference in laboratory evoked pain response between placebo and naloxone drug conditions), and 3) test the effects of the intervention on morphine responses (indexed by the difference in evoked pain response between placebo and morphine laboratory drug conditions).

This project will determine whether enhancing endogenous opioids (via aerobic exercise training) permits achieving desired levels of analgesia with lower dosages of opioid analgesics, and fewer side effects and abuse-relevant drug effects. This 4 year project will test study hypotheses in a sample of 116 chronic low back pain patients. The study will have two key elements: 1) a randomized, controlled aerobic exercise manipulation in CP patients completing daily electronic pain diaries and 2) laboratory evoked thermal pain protocols pre- and post-exercise permitting direct examination of changes in both opioid analgesic effects (in response to a series of incremental morphine doses) and EO activity (indexed by comparing pain responses after placebo vs. opioid blockade).

The study will use a 6 week supervised aerobic exercise manipulation, with subjects randomly assigned to the exercise protocol or a no exercise control condition.

The study will employ a mixed between/within-subjects design using double-blind, counterbalanced, placebo-controlled administration of both an opioid antagonist (naloxone) and an opioid agonist (morphine). All participants will undergo three identical laboratory pain-induction sessions (each ≈5 days apart) prior to randomization to experimental condition, and again at the end of the 6 week exercise manipulation period (regardless of exercise group assignment) during which they will receive the 3 study drugs and participate in controlled laboratory evaluation of evoked thermal pain responsiveness.

Study Design

Study Type:
Interventional
Actual Enrollment :
117 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Reduced Opioid Analgesic Requirements Via Improved Endogenous Opioid Function
Study Start Date :
Aug 1, 2015
Actual Primary Completion Date :
Sep 1, 2019
Actual Study Completion Date :
Sep 1, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: 6 week aerobic exercise intervention

Participants randomly assigned to the exercise condition will complete an 18 session aerobic exercise manipulation supervised by an American College of Sports Medicine-certified personal trainer (3 exercise sessions per week for 6 weeks). Immediately before and after participating in this intervention arm, participants will undergo laboratory evoked thermal pain response testing with placebo-controlled morphine and naloxone administration to assess mechanisms of exercise-related changes.

Behavioral: 6 week aerobic exercise intervention
Participants randomly assigned to the 6 week aerobic exercise intervention will complete an 18 session aerobic exercise manipulation supervised by an American College of Sports Medicine-certified personal trainer (3 exercise sessions per week for 6 weeks). Each exercise session will consist of a 5 minute warm-up, 30 minutes of aerobic exercise, followed by a 5 minute cool-down period. Aerobic exercise will consist of treadmill walking/running, stepping, elliptical, or cycling exercise as preferred by the participant. Duration of exercise will be standardized at 30 minutes with a target exercise intensity between 70-85% Heart Rate Reserve (RPE = 15, hard). Because of the focus on de-conditioned individuals with Chronic Low Back Pain, the duration and intensity of exercise will be progressively increased up to target during the first two weeks to avoid symptom exacerbation and minimize study drop-out.

Drug: Placebo
In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will undergo laboratory evoked thermal pain response testing with: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each).
Other Names:
  • normal saline placebo

    • Drug: Morphine
    In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will undergo laboratory evoked thermal pain response testing with: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each).
    Other Names:
  • Astramorph

    • Drug: naloxone
    In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will undergo laboratory evoked thermal pain response testing with: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each).
    Other Names:
  • narcan

    		•
    Active Comparator: Normal exercise (control)

    Participants assigned to the control condition will not undergo any exercise manipulation during this 6 week period, and will be asked to continue their current activity levels and not engage in any additional exercise activity during the study period. Immediately before and after participating in this intervention arm, participants will undergo laboratory evoked thermal pain response testing with placebo-controlled morphine and naloxone administration to assess mechanisms of exercise-related changes.

    Drug: Placebo
    In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will undergo laboratory evoked thermal pain response testing with: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each).
    Other Names:
  • normal saline placebo

    • Drug: Morphine
    In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will undergo laboratory evoked thermal pain response testing with: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each).
    Other Names:
  • Astramorph

    • Drug: naloxone
    In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will undergo laboratory evoked thermal pain response testing with: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each).
    Other Names:
  • narcan

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Mean of the Change in Morphine Dosage (in mg) Required to Achieve 25% Reduction in Thermal Evoked Pain Responses Relative to Baseline (Pre-intervention) Placebo Condition Responses [At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)]

      At a laboratory testing day pre and post intervention each participant received morphine sulphate (0.3mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02 mg/kg each with testing for thermal evoked pain response. Weight adjusted dosing was used by multiplying the weight of each patient in kg by 0.3mg (dose 1 only) or by .02mg (doses 2-4), with all doses infused in 20mL saline vehicle. Mean of the change in morphine dosage required to achieve 25 % reduction in thermal evoked pain responses on testing day at baseline (pre-intervention) and post intervention. Positive values for the change in the mean between pre and post intervention indicated decreased morphine requirements post intervention.

    2. Mean Change in 5-day Electronic Diary Ratings of Low Back Pain Intensity [At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)]

      Mean change in 5-day electronic diary ratings of low back pain intensity from pre intervention baseline to post intervention. 9 point pain scale assessing pain intensity with 0 represents no pain and 8 represents worst possible pain. Positive values indicate reduced pain post intervention.

    Secondary Outcome Measures

    1. Mean Change in Placebo Condition Ratings of Acute Thermal Pain Intensity on the McGill Pain Questionnaire-Short Form [At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)]

      Mean change in placebo condition ratings of acute thermal pain intensity using the McGill Pain Questionnaire-Short Form on 3 testing days at baseline (per intervention) and post intervention. The score ranges from 0-33 where 0 represents no pain and 33 represents most intense pain. Positive change values indicate decreased pain responsiveness post intervention.

    2. Mean Within-participant Changes From Pre- to Post-intervention in Opioid Blockade Effects (Within-participant Difference Between Naloxone and Placebo Conditions) for Ratings of Acute Thermal Pain Intensity on the McGill Pain Questionnaire-Short Form [At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)]

      Between-participant (aerobic exercise vs. control group) comparison of mean changes from pre- to post-intervention in opioid blockade effects for ratings of acute thermal pain intensity on the McGill Pain Questionnaire-Short Form based on 3 laboratory testing days at baseline (pre-intervention) and post intervention. The score ranges from 0-33 where 0 represents no pain and 33 represents more intense pain. Positive values indicate increased endogenous opioid analgesia post intervention. This measure will test for endogenous opioid mechanisms of the exercise (versus control) intervention as indexed by changes in opioid blockade effects (the difference in laboratory evoked pain response evoked between placebo and naloxone drug conditions). This is a mixed within-between subject design. Per the study protocol, the intent of outcome measures 4 and 6 was to capture opioid blockade effects (within-participant placebo-naloxone condition difference scores) at both the pre- and post-in

    3. Mean Change in McGill Pain Questionnaire-2 Total Chronic Back Pain Ratings [At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)]

      Mean change in McGill Pain Questionnaire-2 total chronic back pain ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-10 where 0 represents no pain and 10 represents most intense pain. Positive values indicate decreased back pain post intervention.

    4. Mean Within-participant Changes From Pre- to Post-intervention in Opioid Blockade Effects (Within-participant Difference Between Naloxone and Placebo Conditions) for McGill Pain Questionnaire-2 Total Ratings of Back Pain. [At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)]

      Between-participant (aerobic exercise vs. control group) comparison of mean changes from pre- to post-intervention in opioid blockade effects for McGill Pain Questionnaire-2 Total ratings of back pain based on 3 laboratory testing days at baseline (pre intervention) and post intervention. The score ranges from 0-10 where 0 represents no pain and 10 represents most intense pain. Positive values indicate increased endogenous opioid analgesia post intervention. This measure will test the effects of the exercise (versus control) intervention on clinical outcomes as indexed by changes in opioid blockade effects (the difference in laboratory evoked pain response evoked between placebo and naloxone drug conditions). This is a mixed within-between subject design. Per the study protocol, the intent of outcome measures 4 and 6 was to capture opioid blockade effects (within-participant placebo-naloxone condition difference scores) at both the pre- and post-intervention lab assessments, an

    5. Mean Change in Positive and Negative Affect Scale-Negative Affect Subscale Ratings. [At pre intervention baseline and again post-intervention (an expected average of 6 weeks later)]

      Mean change in Positive and Negative Affect Scale-Negative Affect subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. . Scale ratings range from 10 to 50 where 10 represents lowest negative affect possible and 50 represents highest negative affect possible. Positive values indicate decreased negative affect post intervention.

    6. Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects Scale-Euphoria Subscale Ratings [At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)]

      Mean change in morphine condition VAS Opioid Effects-Euphoria subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-300 where 0 means no euphoria and 300 means most euphoria possible. Positive values indicate decreased euphoria post intervention.

    7. Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects Scale-Sedation Subscale Ratings [At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)]

      Mean change in morphine condition VAS Opioid Effects-Sedation subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-300 where 0 means no sedation and 300 means most sedation possible. Positive values indicate decreased sedation post intervention.

    8. Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects - Unpleasantness Subscale Ratings [At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)]

      Mean change in morphine condition VAS Opioid Effects - Unpleasantness subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-300 where 0 represents no unpleasantness and 300 represents most unpleasantness possible. Positive values indicate decreased unpleasantness post intervention.

    9. Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Drug Effect Subscale Ratings [At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)]

      Mean change in morphine condition Drug Effects, Liking, and Take Again (DELTA) -Drug Effect subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 1-5 where 1 represents no effect and 5 represents very strong effect. Positive values indicate decreased overall drug effects post intervention.

    10. Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Drug Liking Subscale Ratings [At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)]

      Mean change in morphine condition Drug Effects, Liking, and Take Again (DELTA) -Drug Liking subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-100 where 0 represents dislike a lot and 100 represents like a lot. Positive values indicate decreased drug liking post intervention.

    11. Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Take Again Subscale Ratings [At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)]

      Mean change in morphine condition Drug Effects, Liking, and Take Again (DELTA) -Take Again subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-100 where 0 represents definitely would not take again and 100 represents definitely would take again. Positive values indicate decreased desire to take the drug again post intervention.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 55 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Intact cognitive status and ability to provide informed consent

    • Ability to read and write in English sufficiently to understand and complete study questionnaires

    • Age 18-55 inclusive

    • Presence of persistent daily low back pain of at least three months duration and of at least a 3/10 in average intensity

    Exclusion Criteria:

    • Engagement in > 2 days/wk and > 60 min/wk of moderate or vigorous intensity activity based on responses to 6 validated survey questions at screening (CDC BRFSS)

    • History of renal or hepatic dysfunction

    • Current or past alcohol or substance dependence

    • A history of PTSD, psychotic, or bipolar disorders

    • Chronic pain due to malignancy (e.g., cancer), autoimmune disorders (e.g., rheumatoid arthritis, lupus), or fibromyalgia

    • Recent daily opiate use

    • Use of any opioid analgesic medications within 72 hours of study participation (confirmed through rapid urine screening conducted prior to study participation)

    • Females who are pregnant

    • History of cardiovascular disease (including myocardial infarction)

    • History of seizure disorder

    • Prior allergic reaction/intolerance to morphine or its analogs

    • Presence of cardiac disease or any other medical condition that would make engaging in the aerobic exercise manipulation unsafe

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Rush University Chicago Illinois United States 60612
    2 Vanderbilt University Nashville Tennessee United States 37212

    Sponsors and Collaborators

    • Vanderbilt University Medical Center
    • National Institute on Drug Abuse (NIDA)

    Investigators

    • Principal Investigator: Stephen Bruehl, PhD, Vanderbilt University Medical Center

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Stephen Bruehl, PhD, Professor of Anesthesiology, Vanderbilt University Medical Center
    ClinicalTrials.gov Identifier:
    NCT02469077
    Other Study ID Numbers:
    • 141862
    • R01DA037891
    First Posted:
    Jun 11, 2015
    Last Update Posted:
    Sep 23, 2020
    Last Verified:
    Sep 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Stephen Bruehl, PhD, Professor of Anesthesiology, Vanderbilt University Medical Center
    Chronic Low Back Pain
    Additional relevant MeSH terms:
    Chronic Pain
    Morphine
    Naloxone

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 117 subjects consented and participated in Visit 1 to evaluate the nature of chronic back pain and confirm eligibility to engage in exercise manipulation. 15 subjects were discontinued from participation following this assessment. 9 additional subjects discontinued during preintervention lab session period.
    Arm/Group Title 6 Week Aerobic Exercise Intervention Normal Exercise (Control)
    Arm/Group Description Participants randomly assigned to the exercise condition will complete an 18 session aerobic exercise manipulation supervised by an American College of Sports Medicine-certified personal trainer (3 exercise sessions per week for 6 weeks). Immediately before and after participating in this intervention arm, participants will undergo laboratory evoked thermal pain response testing with placebo-controlled morphine and naloxone administration to assess mechanisms of exercise-related changes. Participants assigned to the control condition will not undergo any exercise manipulation during this 6 week period, and will be asked to continue their current activity levels and not engage in any additional exercise activity during the study period. Immediately before and after participating in this intervention arm, participants will undergo laboratory evoked thermal pain response testing with placebo-controlled morphine and naloxone administration to assess mechanisms of exercise-related changes.
    Period Title: Pre Randomization - Pre Intervention
    STARTED 44 49
    Pre Intervention Placebo 44 49
    Pre Intervention Morpine 44 49
    Pre Intervention Naloxone 44 49
    COMPLETED 44 49
    NOT COMPLETED 0 0
    Period Title: Pre Randomization - Pre Intervention
    STARTED 44 49
    COMPLETED 40 45
    NOT COMPLETED 4 4
    Period Title: Pre Randomization - Pre Intervention
    STARTED 40 45
    Post Intervention Placebo 39 45
    Post Intervention Morphine 40 45
    Post Intervention Naloxone 39 44
    COMPLETED 38 44
    NOT COMPLETED 2 1

    Baseline Characteristics

    Arm/Group Title Exercise Plus Placebo/Morphine/Naloxone Placebo/Morphine/Naloxone Total
    Arm/Group Description Participants randomly assigned to the exercise condition will complete an 18 session aerobic exercise manipulation supervised by an American College of Sports Medicine certified personal trainer (3 exercise sessions per week for 6 weeks). Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes. exercise: Each exercise session will consist of a 5 minute warm-up, 30 minutes of aerobic exercise, followed by a 5 minute cool-down period. Aerobic exercise will consist of treadmill walking/running, stepping, elliptical, or cycling exercise as preferred by the participant. Duration of exercise will be standardized at 30 minutes with a target exercise intensity between 70-85% Heart Rate Reserve (RPE = 15, hard). Because of the focus on de-conditioned individuals with Chronic Low Back Pain, the duration and intensity of exercise wil Participants assigned to the control condition will not undergo any manipulation during this 6 week period, and will be asked to continue their current activity levels and not engage in any additional exercise activity during the study period. Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes. Placebo: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each) Morphine: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 dose Total of all reporting groups
    Overall Participants 38 44 82
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    38
    100%
    44
    100%
    82
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    20
    52.6%
    28
    63.6%
    48
    58.5%
    Male
    18
    47.4%
    16
    36.4%
    34
    41.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    2
    5.3%
    2
    4.5%
    4
    4.9%
    Not Hispanic or Latino
    36
    94.7%
    39
    88.6%
    75
    91.5%
    Unknown or Not Reported
    0
    0%
    3
    6.8%
    3
    3.7%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    2
    5.3%
    1
    2.3%
    3
    3.7%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    10
    26.3%
    15
    34.1%
    25
    30.5%
    White
    23
    60.5%
    25
    56.8%
    48
    58.5%
    More than one race
    1
    2.6%
    0
    0%
    1
    1.2%
    Unknown or Not Reported
    2
    5.3%
    3
    6.8%
    5
    6.1%
    Region of Enrollment (Count of Participants)
    United States
    38
    100%
    44
    100%
    82
    100%

    Outcome Measures

    1. Primary Outcome
    Title Mean of the Change in Morphine Dosage (in mg) Required to Achieve 25% Reduction in Thermal Evoked Pain Responses Relative to Baseline (Pre-intervention) Placebo Condition Responses
    Description At a laboratory testing day pre and post intervention each participant received morphine sulphate (0.3mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02 mg/kg each with testing for thermal evoked pain response. Weight adjusted dosing was used by multiplying the weight of each patient in kg by 0.3mg (dose 1 only) or by .02mg (doses 2-4), with all doses infused in 20mL saline vehicle. Mean of the change in morphine dosage required to achieve 25 % reduction in thermal evoked pain responses on testing day at baseline (pre-intervention) and post intervention. Positive values for the change in the mean between pre and post intervention indicated decreased morphine requirements post intervention.
    Time Frame At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)

    Outcome Measure Data

    Analysis Population Description
    Data was not available for analysis of 2 participants in the exercise arm and 1 participant in the control arm
    Arm/Group Title 6 Week Aerobic Exercise Intervention Normal Exercise (Control)
    Arm/Group Description Participants randomly assigned to the exercise condition will complete an 18 session aerobic exercise manipulation supervised by an American College of Sports Medicine-certified personal trainer (3 exercise sessions per week for 6 weeks). Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes. exercise: Each exercise session will consist of a 5 minute warm-up, 30 minutes of aerobic exercise, followed by a 5 minute cool-down period. Aerobic exercise will consist of treadmill walking/running, stepping, elliptical, or cycling exercise as preferred by the participant. Duration of exercise will be standardized at 30 minutes with a target exercise intensity between 70-85% Heart Rate Reserve (RPE = 15, hard). Because of the focus on de-conditioned individuals with Chronic Low Back Pain, the duration and intensity of exercise wil Participants assigned to the control condition will not undergo any manipulation during this 6 week period, and will be asked to continue their current activity levels and not engage in any additional exercise activity during the study period. Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes. Placebo: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each) Morphine: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 dose
    Measure Participants 36 43
    Baseline (pre intervention)
    4.17
    (1.82)
    6.34
    (5.63)
    Change after 6 week intervention period
    -1.62
    (4.46)
    0.92
    (5.16)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 6 Week Aerobic Exercise Intervention, Normal Exercise (Control)
    Comments Statistical analysis applies to change after 6 week intervention period
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.12
    Comments
    Method ANCOVA
    Comments
    2. Primary Outcome
    Title Mean Change in 5-day Electronic Diary Ratings of Low Back Pain Intensity
    Description Mean change in 5-day electronic diary ratings of low back pain intensity from pre intervention baseline to post intervention. 9 point pain scale assessing pain intensity with 0 represents no pain and 8 represents worst possible pain. Positive values indicate reduced pain post intervention.
    Time Frame At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)

    Outcome Measure Data

    Analysis Population Description
    Data was not available for analysis of 4 participants in the exercise arm and 11 participants in the control arm
    Arm/Group Title 6 Week Aerobic Exercise Intervention Normal Exercise (Control)
    Arm/Group Description Participants randomly assigned to the exercise condition will complete an 18 session aerobic exercise manipulation supervised by an American College of Sports Medicine-certified personal trainer (3 exercise sessions per week for 6 weeks). Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes. exercise: Each exercise session will consist of a 5 minute warm-up, 30 minutes of aerobic exercise, followed by a 5 minute cool-down period. Aerobic exercise will consist of treadmill walking/running, stepping, elliptical, or cycling exercise as preferred by the participant. Duration of exercise will be standardized at 30 minutes with a target exercise intensity between 70-85% Heart Rate Reserve (RPE = 15, hard). Because of the focus on de-conditioned individuals with Chronic Low Back Pain, the duration and intensity of exercise wil Participants assigned to the control condition will not undergo any manipulation during this 6 week period, and will be asked to continue their current activity levels and not engage in any additional exercise activity during the study period. Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes. Placebo: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each) Morphine: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 dose
    Measure Participants 34 33
    Baseline (pre intervention)
    2.75
    (1.20)
    2.82
    (1.38)
    Change after 6 week intervention period
    0.72
    (1.18)
    0.18
    (0.91)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 6 Week Aerobic Exercise Intervention, Normal Exercise (Control)
    Comments Statistical analysis applies to change after 6 week intervention period
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value .04
    Comments
    Method ANCOVA
    Comments
    3. Secondary Outcome
    Title Mean Change in Placebo Condition Ratings of Acute Thermal Pain Intensity on the McGill Pain Questionnaire-Short Form
    Description Mean change in placebo condition ratings of acute thermal pain intensity using the McGill Pain Questionnaire-Short Form on 3 testing days at baseline (per intervention) and post intervention. The score ranges from 0-33 where 0 represents no pain and 33 represents most intense pain. Positive change values indicate decreased pain responsiveness post intervention.
    Time Frame At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 6 Week Aerobic Exercise Intervention Normal Exercise (Control)
    Arm/Group Description Participants randomly assigned to the exercise condition will complete an 18 session aerobic exercise manipulation supervised by an American College of Sports Medicine-certified personal trainer (3 exercise sessions per week for 6 weeks).Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes. exercise: Each exercise session will consist of a 5 minute warm-up, 30 minutes of aerobic exercise, followed by a 5 minute cool-down period. Aerobic exercise will consist of treadmill walking/running, stepping, elliptical, or cycling exercise as preferred by the participant. Duration of exercise will be standardized at 30 minutes with a target exercise intensity between 70-85% Heart Rate Reserve (RPE = 15, hard). Because of the focus on de-conditioned individuals with Chronic Low Back Pain, the duration and intensity of exercise will Participants assigned to the control condition will not undergo any manipulation during this 6 week period, and will be asked to continue their current activity levels and not engage in any additional exercise activity during the study period. Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes. Placebo: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each) Morphine: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 doses
    Measure Participants 38 44
    Baseline (pre intervention)
    10.23
    (9.17)
    7.83
    (6.11)
    Change after 6 week intervention period
    0.45
    (3.99)
    -2.14
    (4.61)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 6 Week Aerobic Exercise Intervention, Normal Exercise (Control)
    Comments Statistical analysis applies to change after 6 week intervention period
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value .03
    Comments
    Method ANCOVA
    Comments
    4. Secondary Outcome
    Title Mean Within-participant Changes From Pre- to Post-intervention in Opioid Blockade Effects (Within-participant Difference Between Naloxone and Placebo Conditions) for Ratings of Acute Thermal Pain Intensity on the McGill Pain Questionnaire-Short Form
    Description Between-participant (aerobic exercise vs. control group) comparison of mean changes from pre- to post-intervention in opioid blockade effects for ratings of acute thermal pain intensity on the McGill Pain Questionnaire-Short Form based on 3 laboratory testing days at baseline (pre-intervention) and post intervention. The score ranges from 0-33 where 0 represents no pain and 33 represents more intense pain. Positive values indicate increased endogenous opioid analgesia post intervention. This measure will test for endogenous opioid mechanisms of the exercise (versus control) intervention as indexed by changes in opioid blockade effects (the difference in laboratory evoked pain response evoked between placebo and naloxone drug conditions). This is a mixed within-between subject design. Per the study protocol, the intent of outcome measures 4 and 6 was to capture opioid blockade effects (within-participant placebo-naloxone condition difference scores) at both the pre- and post-in
    Time Frame At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 6 Week Aerobic Exercise Intervention Normal Exercise (Control)
    Arm/Group Description Participants randomly assigned to the exercise condition will complete an 18 session aerobic exercise manipulation supervised by American College of Sports Medicine-certified personal trainer (3 exercise sessions per week for 6 weeks). Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise related changes. exercise: Each exercise session will consist of a 5 minute warm-up, 30 minutes of aerobic exercise, followed by a 5 minute cool-down period. Aerobic exercise will consist of treadmill walking/running, stepping, elliptical, or cycling exercise as preferred by the participant. Duration of exercise will be standardized at 30 minutes with a target exercise intensity between 70-85% Heart Rate Reserve (RPE = 15, hard). Because of the focus on de-conditioned individuals with Chronic Low Back Pain, the duration and intensity of exercise wil Participants assigned to the control condition will not undergo any manipulation during this 6 week period, and will be asked to continue their current activity levels and not engage in any additional exercise activity during the study period. Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes. Placebo: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each) Morphine: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 dose
    Measure Participants 38 44
    Baseline (pre intervention)
    -0.33
    (4.55)
    0.92
    (3.81)
    Change after 6 week intervention period
    1.97
    (6.32)
    -0.61
    (5.81)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 6 Week Aerobic Exercise Intervention, Normal Exercise (Control)
    Comments Statistical analysis applies to change after 6 week intervention period
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.17
    Comments
    Method ANCOVA
    Comments
    5. Secondary Outcome
    Title Mean Change in McGill Pain Questionnaire-2 Total Chronic Back Pain Ratings
    Description Mean change in McGill Pain Questionnaire-2 total chronic back pain ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-10 where 0 represents no pain and 10 represents most intense pain. Positive values indicate decreased back pain post intervention.
    Time Frame At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 6 Week Aerobic Exercise Intervention Normal Exercise (Control)
    Arm/Group Description Participants randomly assigned to the exercise condition will complete an 18 session aerobic exercise manipulation supervised by American College of Sports Medicine-certified personal trainer (3 exercise sessions per week for 6 weeks). Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise related changes. exercise: Each exercise session will consist of a 5 minute warm-up, 30 minutes of aerobic exercise, followed by a 5 minute cool-down period. Aerobic exercise will consist of treadmill walking/running, stepping, elliptical, or cycling exercise as preferred by the participant. Duration of exercise will be standardized at 30 minutes with a target exercise intensity between 70-85% Heart Rate Reserve (RPE = 15, hard). Because of the focus on de-conditioned individuals with Chronic Low Back Pain, the duration and intensity of exercise wil Participants assigned to the control condition will not undergo any manipulation during this 6 week period, and will be asked to continue their current activity levels and not engage in any additional exercise activity during the study period. Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes. Placebo: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each) Morphine: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 dose
    Measure Participants 38 44
    Baseline (pre intervention)
    2.66
    (1.65)
    3.01
    (1.78)
    Change after 6 week intervention period
    1.60
    (1.58)
    1.36
    (1.41)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 6 Week Aerobic Exercise Intervention, Normal Exercise (Control)
    Comments Statistical analysis applies to change after 6 week intervention period
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.13
    Comments
    Method ANCOVA
    Comments
    6. Secondary Outcome
    Title Mean Within-participant Changes From Pre- to Post-intervention in Opioid Blockade Effects (Within-participant Difference Between Naloxone and Placebo Conditions) for McGill Pain Questionnaire-2 Total Ratings of Back Pain.
    Description Between-participant (aerobic exercise vs. control group) comparison of mean changes from pre- to post-intervention in opioid blockade effects for McGill Pain Questionnaire-2 Total ratings of back pain based on 3 laboratory testing days at baseline (pre intervention) and post intervention. The score ranges from 0-10 where 0 represents no pain and 10 represents most intense pain. Positive values indicate increased endogenous opioid analgesia post intervention. This measure will test the effects of the exercise (versus control) intervention on clinical outcomes as indexed by changes in opioid blockade effects (the difference in laboratory evoked pain response evoked between placebo and naloxone drug conditions). This is a mixed within-between subject design. Per the study protocol, the intent of outcome measures 4 and 6 was to capture opioid blockade effects (within-participant placebo-naloxone condition difference scores) at both the pre- and post-intervention lab assessments, an
    Time Frame At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 6 Week Aerobic Exercise Intervention Normal Exercise (Control)
    Arm/Group Description Participants randomly assigned to the exercise condition will complete an 18 session aerobic exercise manipulation supervised by American College of Sports Medicine-certified personal trainer (3 exercise sessions per week for 6 weeks). Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise related changes. exercise: Each exercise session will consist of a 5 minute warm-up, 30 minutes of aerobic exercise, followed by a 5 minute cool-down period. Aerobic exercise will consist of treadmill walking/running, stepping, elliptical, or cycling exercise as preferred by the participant. Duration of exercise will be standardized at 30 minutes with a target exercise intensity between 70-85% Heart Rate Reserve (RPE = 15, hard). Because of the focus on de-conditioned individuals with Chronic Low Back Pain, the duration and intensity of exercise wil Participants assigned to the control condition will not undergo any manipulation during this 6 week period, and will be asked to continue their current activity levels and not engage in any additional exercise activity during the study period. Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes. Placebo: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each) Morphine: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 dose
    Measure Participants 38 44
    Baseline (pre intervention)
    0.11
    (0.82)
    0.18
    (0.69)
    Change after 6 week intervention period
    -0.12
    (0.96)
    -0.24
    (1.28)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 6 Week Aerobic Exercise Intervention, Normal Exercise (Control)
    Comments Statistical analysis applies to change after 6 week intervention period
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value .98
    Comments
    Method ANCOVA
    Comments
    7. Secondary Outcome
    Title Mean Change in Positive and Negative Affect Scale-Negative Affect Subscale Ratings.
    Description Mean change in Positive and Negative Affect Scale-Negative Affect subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. . Scale ratings range from 10 to 50 where 10 represents lowest negative affect possible and 50 represents highest negative affect possible. Positive values indicate decreased negative affect post intervention.
    Time Frame At pre intervention baseline and again post-intervention (an expected average of 6 weeks later)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 6 Week Aerobic Exercise Intervention Normal Exercise (Control)
    Arm/Group Description Participants randomly assigned to the exercise condition will complete an 18 session aerobic exercise manipulation supervised by American College of Sports Medicine-certified personal trainer (3 exercise sessions per week for 6 weeks). Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise related changes. exercise: Each exercise session will consist of a 5 minute warm-up, 30 minutes of aerobic exercise, followed by a 5 minute cool-down period. Aerobic exercise will consist of treadmill walking/running, stepping, elliptical, or cycling exercise as preferred by the participant. Duration of exercise will be standardized at 30 minutes with a target exercise intensity between 70-85% Heart Rate Reserve (RPE = 15, hard). Because of the focus on de-conditioned individuals with Chronic Low Back Pain, the duration and intensity of exercise wil Participants assigned to the control condition will not undergo any manipulation during this 6 week period, and will be asked to continue their current activity levels and not engage in any additional exercise activity during the study period. Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes. Placebo: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each) Morphine: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 dose
    Measure Participants 38 44
    Baseline (pre intervention)
    16.38
    (5.85)
    15.43
    (4.52)
    Change after 6 week intervention period
    0.45
    (3.99)
    -2.14
    (4.61)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 6 Week Aerobic Exercise Intervention, Normal Exercise (Control)
    Comments Statistical analysis applies to change after 6 week intervention period
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.52
    Comments
    Method ANCOVA
    Comments
    8. Secondary Outcome
    Title Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects Scale-Euphoria Subscale Ratings
    Description Mean change in morphine condition VAS Opioid Effects-Euphoria subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-300 where 0 means no euphoria and 300 means most euphoria possible. Positive values indicate decreased euphoria post intervention.
    Time Frame At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 6 Week Aerobic Exercise Intervention Normal Exercise (Control)
    Arm/Group Description Participants randomly assigned to the exercise condition will complete an 18 session aerobic exercise manipulation supervised by American College of Sports Medicine-certified personal trainer (3 exercise sessions per week for 6 weeks). Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise related changes. exercise: Each exercise session will consist of a 5 minute warm-up, 30 minutes of aerobic exercise, followed by a 5 minute cool-down period. Aerobic exercise will consist of treadmill walking/running, stepping, elliptical, or cycling exercise as preferred by the participant. Duration of exercise will be standardized at 30 minutes with a target exercise intensity between 70-85% Heart Rate Reserve (RPE = 15, hard). Because of the focus on de-conditioned individuals with Chronic Low Back Pain, the duration and intensity of exercise wil Participants assigned to the control condition will not undergo any manipulation during this 6 week period, and will be asked to continue their current activity levels and not engage in any additional exercise activity during the study period. Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes. Placebo: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each) Morphine: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 dose
    Measure Participants 38 44
    Baseline (pre intervention)
    100.60
    (70.35)
    108.24
    (81.27)
    Change after 6 week intervention period
    3.19
    (47.91)
    0.75
    (50.17)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 6 Week Aerobic Exercise Intervention, Normal Exercise (Control)
    Comments Statistical analysis applies to change after 6 week intervention period
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.65
    Comments
    Method ANCOVA
    Comments
    9. Secondary Outcome
    Title Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects Scale-Sedation Subscale Ratings
    Description Mean change in morphine condition VAS Opioid Effects-Sedation subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-300 where 0 means no sedation and 300 means most sedation possible. Positive values indicate decreased sedation post intervention.
    Time Frame At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 6 Week Aerobic Exercise Intervention Normal Exercise (Control)
    Arm/Group Description Participants randomly assigned to the exercise condition will complete an 18 session aerobic exercise manipulation supervised by American College of Sports Medicine-certified personal trainer (3 exercise sessions per week for 6 weeks). Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise related changes. exercise: Each exercise session will consist of a 5 minute warm-up, 30 minutes of aerobic exercise, followed by a 5 minute cool-down period. Aerobic exercise will consist of treadmill walking/running, stepping, elliptical, or cycling exercise as preferred by the participant. Duration of exercise will be standardized at 30 minutes with a target exercise intensity between 70-85% Heart Rate Reserve (RPE = 15, hard). Because of the focus on de-conditioned individuals with Chronic Low Back Pain, the duration and intensity of exercise wil Participants assigned to the control condition will not undergo any manipulation during this 6 week period, and will be asked to continue their current activity levels and not engage in any additional exercise activity during the study period. Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes. Placebo: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each) Morphine: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 dose
    Measure Participants 38 44
    Baseline (pre intervention)
    66.58
    (71.54)
    30.63
    (53.54)
    Change after 6 week intervention period
    12.89
    (55.30)
    -9.95
    (38.033)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 6 Week Aerobic Exercise Intervention, Normal Exercise (Control)
    Comments Statistical analysis applies to change after 6 week intervention period
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1
    Comments
    Method ANCOVA
    Comments
    10. Secondary Outcome
    Title Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects - Unpleasantness Subscale Ratings
    Description Mean change in morphine condition VAS Opioid Effects - Unpleasantness subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-300 where 0 represents no unpleasantness and 300 represents most unpleasantness possible. Positive values indicate decreased unpleasantness post intervention.
    Time Frame At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 6 Week Aerobic Exercise Intervention Normal Exercise (Control)
    Arm/Group Description Participants randomly assigned to the exercise condition will complete an 18 session aerobic exercise manipulation supervised by American College of Sports Medicine-certified personal trainer (3 exercise sessions per week for 6 weeks). Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise related changes. exercise: Each exercise session will consist of a 5 minute warm-up, 30 minutes of aerobic exercise, followed by a 5 minute cool-down period. Aerobic exercise will consist of treadmill walking/running, stepping, elliptical, or cycling exercise as preferred by the participant. Duration of exercise will be standardized at 30 minutes with a target exercise intensity between 70-85% Heart Rate Reserve (RPE = 15, hard). Because of the focus on de-conditioned individuals with Chronic Low Back Pain, the duration and intensity of exercise wil Participants assigned to the control condition will not undergo any manipulation during this 6 week period, and will be asked to continue their current activity levels and not engage in any additional exercise activity during the study period. Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes. Placebo: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each) Morphine: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 dose
    Measure Participants 38 44
    Baseline (pre intervention)
    33.58
    (36.33)
    16.52
    (24.95)
    Change after 6 week intervention period
    -3.21
    (38.43)
    1.86
    (17.99)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 6 Week Aerobic Exercise Intervention, Normal Exercise (Control)
    Comments Statistical analysis applies to change after 6 week intervention period
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value .046
    Comments
    Method ANCOVA
    Comments
    11. Secondary Outcome
    Title Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Drug Effect Subscale Ratings
    Description Mean change in morphine condition Drug Effects, Liking, and Take Again (DELTA) -Drug Effect subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 1-5 where 1 represents no effect and 5 represents very strong effect. Positive values indicate decreased overall drug effects post intervention.
    Time Frame At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 6 Week Aerobic Exercise Intervention Normal Exercise (Control)
    Arm/Group Description Participants randomly assigned to the exercise condition will complete an 18 session aerobic exercise manipulation supervised by an American College of Sports Medicine certified personal trainer (3 exercise sessions per week for 6 weeks). Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes. exercise: Each exercise session will consist of a 5 minute warm-up, 30 minutes of aerobic exercise, followed by a 5 minute cool-down period. Aerobic exercise will consist of treadmill walking/running, stepping, elliptical, or cycling exercise as preferred by the participant. Duration of exercise will be standardized at 30 minutes with a target exercise intensity between 70-85% Heart Rate Reserve (RPE = 15, hard). Because of the focus on de-conditioned individuals with Chronic Low Back Pain, the duration and intensity of exercise wil Participants assigned to the control condition will not undergo any manipulation during this 6 week period, and will be asked to continue their current activity levels and not engage in any additional exercise activity during the study period. Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes. Placebo: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each) Morphine: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 dose
    Measure Participants 38 44
    Baseline (pre intervention)
    2.72
    (0.99)
    2.52
    (1.00)
    Change after 6 week intervention period
    0.10
    (1.19)
    -0.12
    (0.79)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 6 Week Aerobic Exercise Intervention, Normal Exercise (Control)
    Comments Statistical analysis applies to change after 6 week intervention period
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.61
    Comments
    Method ANCOVA
    Comments
    12. Secondary Outcome
    Title Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Drug Liking Subscale Ratings
    Description Mean change in morphine condition Drug Effects, Liking, and Take Again (DELTA) -Drug Liking subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-100 where 0 represents dislike a lot and 100 represents like a lot. Positive values indicate decreased drug liking post intervention.
    Time Frame At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 6 Week Aerobic Exercise Intervention Normal Exercise (Control)
    Arm/Group Description Participants randomly assigned to the exercise condition will complete an 18 session aerobic exercise manipulation supervised by an American College of Sports Medicine certified personal trainer (3 exercise sessions per week for 6 weeks). Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes. exercise: Each exercise session will consist of a 5 minute warm-up, 30 minutes of aerobic exercise, followed by a 5 minute cool-down period. Aerobic exercise will consist of treadmill walking/running, stepping, elliptical, or cycling exercise as preferred by the participant. Duration of exercise will be standardized at 30 minutes with a target exercise intensity between 70-85% Heart Rate Reserve (RPE = 15, hard). Because of the focus on de-conditioned individuals with Chronic Low Back Pain, the duration and intensity of exercise wil Participants assigned to the control condition will not undergo any manipulation during this 6 week period, and will be asked to continue their current activity levels and not engage in any additional exercise activity during the study period. Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes. Placebo: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each) Morphine: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 dose
    Measure Participants 38 44
    Baseline (pre intervention)
    52.03
    (12.52)
    52.89
    (17.57)
    Change after 6 week intervention period
    4.13
    (15.50)
    1.04
    (18.68)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 6 Week Aerobic Exercise Intervention, Normal Exercise (Control)
    Comments Statistical analysis applies to change after 6 week intervention period
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4
    Comments
    Method ANCOVA
    Comments
    13. Secondary Outcome
    Title Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Take Again Subscale Ratings
    Description Mean change in morphine condition Drug Effects, Liking, and Take Again (DELTA) -Take Again subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-100 where 0 represents definitely would not take again and 100 represents definitely would take again. Positive values indicate decreased desire to take the drug again post intervention.
    Time Frame At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 6 Week Aerobic Exercise Intervention Normal Exercise (Control)
    Arm/Group Description Participants randomly assigned to the exercise condition will complete an 18 session aerobic exercise manipulation supervised by an American College of Sports Medicine certified personal trainer (3 exercise sessions per week for 6 weeks). Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes. exercise: Each exercise session will consist of a 5 minute warm-up, 30 minutes of aerobic exercise, followed by a 5 minute cool-down period. Aerobic exercise will consist of treadmill walking/running, stepping, elliptical, or cycling exercise as preferred by the participant. Duration of exercise will be standardized at 30 minutes with a target exercise intensity between 70-85% Heart Rate Reserve (RPE = 15, hard). Because of the focus on de-conditioned individuals with Chronic Low Back Pain, the duration and intensity of exercise wil Participants assigned to the control condition will not undergo any manipulation during this 6 week period, and will be asked to continue their current activity levels and not engage in any additional exercise activity during the study period. Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes. Placebo: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each) Morphine: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 dose
    Measure Participants 38 44
    Baseline (pre intervention)
    54.49
    (14.54)
    55.04
    (22.93)
    Change after 6 week intervention period
    4.40
    (19.72)
    1.70
    (22.56)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 6 Week Aerobic Exercise Intervention, Normal Exercise (Control)
    Comments Statistical analysis applies to change after 6 week intervention period
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.57
    Comments
    Method ANCOVA
    Comments

    Adverse Events

    Time Frame Adverse event data was collected from consent to the completion of the last study visit.(approximately 12 weeks).
    Adverse Event Reporting Description
    Arm/Group Title Exercise Plus Placebo/Morphine/Naloxone Placebo/Morphine/Naloxone
    Arm/Group Description Participants randomly assigned to the exercise condition will complete an 18 session aerobic exercise manipulation supervised by an American College of Sports Medicine certified personal trainer (3 exercise sessions per week for 6 weeks). Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes. exercise: Each exercise session will consist of a 5 minute warm-up, 30 minutes of aerobic exercise, followed by a 5 minute cool-down period. Aerobic exercise will consist of treadmill walking/running, stepping, elliptical, or cycling exercise as preferred by the participant. Duration of exercise will be standardized at 30 minutes with a target exercise intensity between 70-85% Heart Rate Reserve (RPE = 15, hard). Because of the focus on de-conditioned individuals with Chronic Low Back Pain, the duration and intensity of exercise wil Participants assigned to the control condition will not undergo any manipulation during this 6 week period, and will be asked to continue their current activity levels and not engage in any additional exercise activity during the study period. Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes. Placebo: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each) Morphine: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 dose
    All Cause Mortality
    Exercise Plus Placebo/Morphine/Naloxone Placebo/Morphine/Naloxone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/38 (0%) 0/44 (0%)
    Serious Adverse Events
    Exercise Plus Placebo/Morphine/Naloxone Placebo/Morphine/Naloxone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/38 (0%) 0/44 (0%)
    Other (Not Including Serious) Adverse Events
    Exercise Plus Placebo/Morphine/Naloxone Placebo/Morphine/Naloxone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/38 (0%) 0/44 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Stephen Bruehl, Ph.D.
    Organization Vanderbilt University Medical Center
    Phone 615-936-1821
    Email stephen.bruehl@vumc.org
    Responsible Party:
    Stephen Bruehl, PhD, Professor of Anesthesiology, Vanderbilt University Medical Center
    ClinicalTrials.gov Identifier:
    NCT02469077
    Other Study ID Numbers:
    • 141862
    • R01DA037891
    First Posted:
    Jun 11, 2015
    Last Update Posted:
    Sep 23, 2020
    Last Verified:
    Sep 1, 2020