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MEDEX: A Multi-level Life-span Characterization of Adult-depression and Effects of Medication and Exercise

Sponsor
Kirk Erickson, PhD (Other)
Overall Status
Completed
CT.gov ID
NCT02407704
Collaborator
(none)
31
Enrollment
1
Location
2
Arms
21.1
Duration (Months)
1.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This pilot study aims to test a model that predicts that enhanced neurotransmitter gamma-aminobutyric acid (GABA) function in reward and affect-regulation central nervous system (CNS) circuits mediates the antidepressant effects of exercise. State-of-the-art magnetic resonance (MR) imaging, cognitive assessment, accelerometry, genetic, and inflammatory biomarkers will be acquired through the coordination of efforts from several established research programs at Western Psychiatric Institute and Clinic. This pilot study will be used as a platform for testing a causal/mediating role of GABA interneurons in reward processing and affect regulation in humans. This pilot study is not powered for testing a full causal model, but rather is intended to test overall feasibility of the intervention and acquisition of measures (see specific aim 1 below). This is a necessary prerequisite for designing a larger more definitive study of the model, which will be a component of a future grant application. Additionally, the data from this study will be used to test the clinical efficacy of exercise as an adjunctive treatment for late life depression (LLD; Specific Aim 2), as well as imaging, cognitive, and sleep aims (Specific Aims 3 and 4).

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

Specific Aims:

Aim 1: Establish the infrastructure, protocol, and procedures for recruiting, screening, enrolling, and maintaining a sample of 30 adults (both younger adults and older adults) with major depression in a 12-week exercise intervention. The primary aim is to establish both feasibility and proof-of-concept on a wide range of biologically and clinically relevant outcomes.

Aim 2: Examine whether the 12-week physical activity + pharmacotherapy intervention reduces depressive symptoms in both younger and older adults above and beyond that of treatment as usual (TAU). Hypothesis 1: In both younger and older adults the antidepressant properties of pharmacotherapy will be augmented when combined with aerobic exercise such that the combined intervention will have higher rates of response and remission compared to only pharmacotherapy treatment.

Aim 3: Examine whether the 12-week combined physical activity and pharmacotherapy intervention changes the structural morphology in specific subfields of the hippocampus. Hypothesis 1: The medication intervention will increase hippocampal volume in the dentate gyrus and carbonic anhydrase I (CA1), but combining aerobic exercise with pharmacotherapy will magnify the effects of exercise. Hypothesis 2: The effect on hippocampal volume will be larger for older versus younger adults Aim 4: Explore how the combination of pharmacotherapy and exercise (compared with pharmacotherapy and TAU) influences a range of brain and behavioral outcomes, including resting state brain dynamics, MR spectroscopic measures of GABA, sleep efficiency, and cognitive performance. Hypothesis 1: Antidepressant pharmacotherapy will alter resting state networks, increase GABA levels, and improve sleep efficiency and cognitive performance - but these effects will be greater when combined with an aerobic exercise intervention. Hypothesis 2: These effects will be moderated by age such that the effects will be greater in older adults, supporting a dissociation between depression in younger and adults, and providing justification for fully powered study to explore these models and treatment-predictive biomarkers.

Depression is a significant global public health concern; it is the second leading cause of disability worldwide and is currently estimated to affect 350 million people. Antidepressant medications have shown to be more effective than placebo in treating depression. However, for 20-40% of individuals suffering from depression the pharmacotherapy has a slow or inadequate response. Thus, identifying alternative treatments for depression is a public health priority.

Background:

Physical activity is emerging as one of the most promising non-pharmaceutical treatments for depression. Greater amounts of self-reported physical activity are associated with fewer depressive symptoms in epidemiological studies and randomized interventions find that participation in physical activity enhances mood in depressed populations. A Cochrane review of 32 randomized interventions concluded that participation in physical activity is effective for reducing depressive symptoms compared to either no treatment or to a control condition. Importantly, antidepressants and physical activity may work through similar biological pathways to influence both mood and cognitive function. In fact, both antidepressants and physical activity increase levels of Brain-derived neurotrophic factor (BDNF) in serum and hippocampus, may mitigate or reverse hippocampal atrophy, influence expression and kinetics of serotonin and GABA pathways, regulate brain network connectivity, alter inflammatory pathways, and improve sleep efficiency. Our proposal aims to characterize these effects from the genetic to the behavioral and cognitive level, and isolate the effects of physical activity from those of medication.

Significance:

If effective, physical activity could become a first line of treatment for depression, which might also help reduce cognitive deficits, job productivity, and risk of other psychiatric conditions. Furthermore, although physical exercise has shown promise in reducing depressive symptoms, researchers still do not understand the biological pathways by which it works. One of the leading hypotheses of depression is that disruptions in GABA systems underlies the deficits. In contrast, improvements in GABA signaling is one of the ways in which exercise may improve brain function and reduce depressive symptoms. Along this line, investigators hope to determine the type of exercise (aerobic versus stretching and toning) that can be promoted in the future to improve brain function and reduce depressive symptoms. Demonstrating these links could be an important first step for developing more effective treatment plans for those suffering from depression.

Study Design

Study Type:
Interventional
Actual Enrollment :
31 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multi-level Life-span Characterization of Adult-depression and Effects of Medication and Exercise
Study Start Date :
Mar 1, 2015
Actual Primary Completion Date :
Nov 1, 2016
Actual Study Completion Date :
Dec 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Aerobic Exercise + Venlafaxine XR

Venlafaxine (Effexor) Extended-Release (XR) comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Exercise will include walking on a treadmill 1 hour 3 times/week for 12 weeks. Heart rate will be closely monitored during sessions. The intensity of the exercise will start at 50% of the age-based maximum for the first week and then increase and be maintained at 60-70% of the age-based maximum for the remainder of the intervention. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours).

Drug: Venlafaxine XR
Other Names:
  • Effexor XR

    • Other: Aerobic Exercise
    Other Names:
  • Physical Activity
  • Cardiovascular Exercise

    • Drug: Lorazepam
    Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. Patients taking another benzodiazepine will be asked to convert from their current benzodiazepine to an equivalent dose of Lorazepam (2mg or less in 24 hours). This will be administered in pill form.
    Other Names:
  • Ativan

    		•
    Active Comparator: Venlafaxine XR Only

    Venlafaxine (Effexor) XR comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours).

    Drug: Venlafaxine XR
    Other Names:
  • Effexor XR

    • Drug: Lorazepam
    Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. Patients taking another benzodiazepine will be asked to convert from their current benzodiazepine to an equivalent dose of Lorazepam (2mg or less in 24 hours). This will be administered in pill form.
    Other Names:
  • Ativan

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants Experiencing Remission [Baseline, weekly for weeks 1 and 2, then biweekly for weeks 4-12]

      Study completers will be classified as remitters vs. non-remitters. Remission will be defined as a MADRS score of 10 or less for at least two consecutive assessments. The MADRS will also be used to assess clinical response throughout the trial and to determine final medication dosage. At the end of week 6, those with a MADRS score greater than 10 will have the venlafaxine XR increased from 150 mg/d to a maximum of 300 mg/d.

    Secondary Outcome Measures

    1. Inflammatory Biomarkers [Baseline and 12 weeks]

      Blood samples were collected to assess biomarkers, but funding is not yet available to perform analyses.

    2. Genetic Biomarkers [Baseline and 12 weeks]

      Blood samples were collected to assess biomarkers, but funding is not yet available to perform analyses.

    3. Physical Activity (SenseWear Physical Activity-monitoring Armband) [Baseline and 12 weeks]

      This will be used to acquire objective information about physical activity. This armband is worn around the upper arm (left triceps) for 1 week and collects information about skin temperature, galvanic skin response, heat flux, and motion via a 3-axis accelerometer. This information is used in an algorithm to determine energy expenditure (EE). The device has a resolution of 1-minute indicating that we can acquire the above information on a minute-by-minute basis, which will allow us to determine both duration and intensity of activity during a normal week. Higher values indicate higher levels of activity.

    4. Cardiovascular Fitness (Submaximal VO2) [Baseline and 12 weeks]

      Cardiorespiratory fitness was measured via submaximal VO2 on a motorized treadmill while measuring oxygen utilization via Parvo Medics True one metabolic cart. The submaximal test followed a modified Balke protocol in which speed remained constant with the intensity being increased every two minutes via a raise of 2.0% of the incline. The speed was an agreed upon speed between participant and staff (between 2.0 and 4.0 mph). The submaximal VO2 was stopped when participant reached 85% of age predicted maximal heart rate (220 - age), rating of perceived exertion (RPE) equal to or greater than 15 for those who have blunted heart rate response due to beta block medication, or volitional termination by participant. Vital signs were monitored throughout the test and cool down period. Peak VO2 values for this cohort ranged from 14.04 to 36.48 ml/kg/min, with higher values correlated to higher fitness level.

    5. Functional Magnetic Resonance Imaging (fMRI) [Baseline and 12 weeks]

      Brain imaging conducted with a 7 Tesla scanner. Of particular interest were changes in hippocampal volume, GABA, and glutamate. The changes regarding hippocampal volumes are reported below. This measurement is reported in mm^3, with higher numbers indicating higher levels of gray matter in the hippocampal region. Volume is combined between right and left hemispheres. GABA and glutamate are not reported. The method used to obtain the data was being piloted for this study, and due to methodological challenges, the data is not considered to be accurate and therefore cannot be analyzed/shared.

    6. Neurocognitive Function (Neuropsychological Battery) [Baseline and 12 weeks]

      The battery evaluates several cognitive domains. The Wechsler Adult Intelligence Scale, 4th ed. Digit Span subtest assesses attention and working memory. The Repeatable Battery of Neuropsychological Status (RBANS) measures Immediate and Delayed Memory, Attention, Language Abilities, and Visuospatial Functioning. Total index scores range from 40-155. The California Verbal Learning Test, 2nd Ed. (CVLT) assesses non-contextual verbal learning and memory. Z-scores are calculated for each of the constructs assessed by the CVLT. Subtests from the Deli-Kaplan Executive Function System (D-KEFS) assess aspects of executive functioning, including set-shifting (Trail Making Test Conditions 4 and 5: scaled score ranging from 0-19) and inhibition (Color-Word Interference Test Condition 3: weighted scaled score ranging from 1-19). Given that standardized scores are calculated for each of the neuropsychological measures, higher scores always indicate better cognitive functioning.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    60 Years to 79 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Ages 20-39 (recruitment complete) and 60-79 years old (open to recruitment)

    2. Major depressive disorder (MDD), single or recurrent, as diagnosed by the PRIME-MD

    3. MADRS ≥ 15

    4. In-town and available to commute to Oakland for a 12-week period

    5. Study nurse practitioner approval to participate in a 12-week moderate intense exercise intervention

    6. Eligible to undergo MRI

    Exclusion Criteria:

    1. Inability to provide informed consent.

    2. Modified Mini-Mental Score (3MS) less than 84 or dementia based upon Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria including poor performance on the clinical neuropsychological battery, IQCODE, and all available clinical information.

    3. Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms.

    4. Abuse of or dependence on alcohol or other substances within the past three months

    5. High risk for suicide [e.g., active suicidal ideation (SI) and/or current/recent intent or plan] AND unable to be managed safely in the clinical trial (e.g., unwilling to be hospitalized). Urgent psychiatric referral will be made in these cases.

    6. Contraindication to venlafaxine XR as determined by study physician including history of intolerance of venlafaxine XR in the study target dosage range (venlafaxine XR at up to 300 mg/day).

    7. Inability to communicate in English (i.e., interview cannot be conducted without an interpreter; subject largely unable to understand questions and cannot respond in English).

    8. Non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview)

    9. Unstable/uncontrolled medical illness, including delirium, hypertension, hyperlipidemia, or cerebrovascular or cardiovascular risk factors that are not under medical management.

    10. Subjects taking psychotropic medications that cannot be safely tapered or discontinued prior to study initiation

    11. If a patient failed a trial of venlafaxine (12 weeks of treatment with venlafaxine including at least 6 weeks on 300mg/day), he/she would not be eligible.

    12. Other drugs that may affect the GABA system will be excluded (e.g., Kava, Valerian, Theanine, and GABA supplements).

    13. The drug Linezolid (Zyvox) should be discontinued prior to study enrollment and should not be used during the study.

    14. Exclusion criteria for MR scans include: cardiac pacemaker, aneurysm clip, cochlear implant, pregnancy, intrauterine device, shrapnel, history of metal fragments in the eye, neurostimulators, weight >250 lbs., tinnitus, or claustrophobia.

    15. Current medical condition or treatment for a medical condition that could affect balance, gait, or contraindicate participation in moderate intensity physical activity.

    16. Observed gait condition or use of walking assisted device that would contraindicate use of treadmill for exercise testing and intervention.

    17. Current congestive heart failure, angina, uncontrolled arrhythmia, or other symptoms indicative of an increased acute risk for a cardiovascular event; within the previous 12 months having a myocardial infarction, coronary artery bypass grafting, or angioplasty; conditions requiring chronic anticoagulation (i.e. recent or recurrent DVT).

    18. Eating disorders that would contraindicate physical activity.

    19. Report exercise on more than three days per week for greater than 20 minutes per day over the past three months.

    20. Report plans to relocate to a location not accessible to the study site or having employment, personal, or travel commitments that prohibit attendance to at least 80 percent of the scheduled intervention sessions and all of the scheduled assessments.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Pittsburgh Pittsburgh Pennsylvania United States 15213

    Sponsors and Collaborators

    • Kirk Erickson, PhD

    Investigators

    • Principal Investigator: Kirk Erickson, PhD, University of Pittsburgh

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Kirk Erickson, PhD, Associate Professor/Principal Investigator, University of Pittsburgh
    ClinicalTrials.gov Identifier:
    NCT02407704
    Other Study ID Numbers:
    • MH090333-04
    • PRO13110090
    • MH090333
    First Posted:
    Apr 3, 2015
    Last Update Posted:
    May 23, 2018
    Last Verified:
    Apr 1, 2018
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Kirk Erickson, PhD, Associate Professor/Principal Investigator, University of Pittsburgh
    Exercise
    Physical activity
    GABA
    Venlafaxine
    fMRI
    Spectroscopy
    Reward system
    BDNF
    Sleep
    Cognitive function
    Biomarkers
    Aerobic exercise
    Additional relevant MeSH terms:
    Disease
    Depression
    Depressive Disorder
    Depressive Disorder, Major
    Lorazepam
    Venlafaxine Hydrochloride

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Participants were diagnosed using the SCID, and were excluded from participation if they did not meet criteria for Major Depressive Disorder. Participants were also excluded for presence of bipolar or psychotic disorders, alcohol/substance dependence within the past 3 months, or if they could not complete MRI.
    Arm/Group Title Aerobic Exercise + Venlafaxine XR (60-79 Years of Age) Venlafaxine XR Only (60-79 Years of Age) Aerobic Exercise + Venlafaxine XR (20-39 Years of Age) Venlafaxine XR Only (20-39 Years of Age)
    Arm/Group Description Venlafaxine (Effexor) Extended-Release (XR) comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Exercise will include walking on a treadmill 1 hour 3 times/week for 12 weeks. The intensity of the exercise will start at 50% of the age-based maximum for the first week and then increase and be maintained at 60-70% of the age-based maximum for the remainder of the intervention. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Venlafaxine (Effexor) XR comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Lorazepam: Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. Patients taking another benzodiazepine will be asked to convert from their current benzodiazepine to an equivalent dose of Lorazepam (2mg or less in 24 hours). This will be administered in pill form. Venlafaxine (Effexor) Extended-Release (XR) comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Exercise will include walking on a treadmill 1 hour 3 times/week for 12 weeks. The intensity of the exercise will start at 50% of the age-based maximum for the first week and then increase and be maintained at 60-70% of the age-based maximum for the remainder of the intervention. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Venlafaxine (Effexor) XR comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Lorazepam: Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. Patients taking another benzodiazepine will be asked to convert from their current benzodiazepine to an equivalent dose of Lorazepam (2mg or less in 24 hours). This will be administered in pill form.
    Period Title: Overall Study
    STARTED 2 3 5 5
    COMPLETED 2 3 4 2
    NOT COMPLETED 0 0 1 3

    Baseline Characteristics

    Arm/Group Title Aerobic Exercise + Venlafaxine XR (60-79 Years of Age) Venlafaxine XR Only (60-79 Years of Age) Aerobic Exercise + Venlafaxine XR (20-39 Years of Age) Venlafaxine XR Only (20-39 Years of Age) Total
    Arm/Group Description Venlafaxine (Effexor) Extended-Release (XR) comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Exercise will include walking on a treadmill 1 hour 3 times/week for 12 weeks. The intensity of the exercise will start at 50% of the age-based maximum for the first week and then increase and be maintained at 60-70% of the age-based maximum for the remainder of the intervention. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Venlafaxine (Effexor) XR comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Lorazepam: Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. Patients taking another benzodiazepine will be asked to convert from their current benzodiazepine to an equivalent dose of Lorazepam (2mg or less in 24 hours). This will be administered in pill form. Venlafaxine (Effexor) Extended-Release (XR) comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Exercise will include walking on a treadmill 1 hour 3 times/week for 12 weeks. The intensity of the exercise will start at 50% of the age-based maximum for the first week and then increase and be maintained at 60-70% of the age-based maximum for the remainder of the intervention. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Venlafaxine (Effexor) XR comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Lorazepam: Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. Patients taking another benzodiazepine will be asked to convert from their current benzodiazepine to an equivalent dose of Lorazepam (2mg or less in 24 hours). This will be administered in pill form. Total of all reporting groups
    Overall Participants 2 3 5 5 15
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    1
    50%
    1
    33.3%
    5
    100%
    5
    100%
    12
    80%
    >=65 years
    1
    50%
    2
    66.7%
    0
    0%
    0
    0%
    3
    20%
    Sex: Female, Male (Count of Participants)
    Female
    1
    50%
    3
    100%
    3
    60%
    3
    60%
    10
    66.7%
    Male
    1
    50%
    0
    0%
    2
    40%
    2
    40%
    5
    33.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    1
    20%
    0
    0%
    1
    6.7%
    Not Hispanic or Latino
    2
    100%
    3
    100%
    4
    80%
    5
    100%
    14
    93.3%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    1
    50%
    0
    0%
    1
    20%
    1
    20%
    3
    20%
    White
    1
    50%
    3
    100%
    3
    60%
    4
    80%
    11
    73.3%
    More than one race
    0
    0%
    0
    0%
    1
    20%
    0
    0%
    1
    6.7%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Count of Participants)
    United States
    2
    100%
    3
    100%
    5
    100%
    5
    100%
    15
    100%
    Montgomery Asberg Depression Rating Scale (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    27.00
    (0.71)
    24.33
    (3.51)
    21.80
    (5.81)
    25.60
    (4.55)
    23.73
    (4.23)

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants Experiencing Remission
    Description Study completers will be classified as remitters vs. non-remitters. Remission will be defined as a MADRS score of 10 or less for at least two consecutive assessments. The MADRS will also be used to assess clinical response throughout the trial and to determine final medication dosage. At the end of week 6, those with a MADRS score greater than 10 will have the venlafaxine XR increased from 150 mg/d to a maximum of 300 mg/d.
    Time Frame Baseline, weekly for weeks 1 and 2, then biweekly for weeks 4-12

    Outcome Measure Data

    Analysis Population Description
    1 participant in the "Venlafaxine XR Only (20-39 Years of Age)" group was excluded from analyses as he/she discontinued the medication after week 8.
    Arm/Group Title Aerobic Exercise + Venlafaxine XR (60-79 Years of Age) Venlafaxine XR Only (60-79 Years of Age) Aerobic Exercise + Venlafaxine XR (20-39 Years of Age) Venlafaxine XR Only (20-39 Years of Age)
    Arm/Group Description Venlafaxine (Effexor) Extended-Release (XR) comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Exercise will include walking on a treadmill 1 hour 3 times/week for 12 weeks. The intensity of the exercise will start at 50% of the age-based maximum for the first week and then increase and be maintained at 60-70% of the age-based maximum for the remainder of the intervention. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Venlafaxine (Effexor) XR comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. Patients taking another benzodiazepine will be asked to convert from their current benzodiazepine to an equivalent dose of Lorazepam (2mg or less in 24 hours). This will be administered in pill form. Venlafaxine (Effexor) Extended-Release (XR) comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Exercise will include walking on a treadmill 1 hour 3 times/week for 12 weeks. The intensity of the exercise will start at 50% of the age-based maximum for the first week and then increase and be maintained at 60-70% of the age-based maximum for the remainder of the intervention. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Venlafaxine (Effexor) XR comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. Patients taking another benzodiazepine will be asked to convert from their current benzodiazepine to an equivalent dose of Lorazepam (2mg or less in 24 hours). This will be administered in pill form.
    Measure Participants 2 3 4 2
    Count of Participants [Participants]
    0
    0%
    2
    66.7%
    4
    80%
    2
    40%
    2. Secondary Outcome
    Title Inflammatory Biomarkers
    Description Blood samples were collected to assess biomarkers, but funding is not yet available to perform analyses.
    Time Frame Baseline and 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aerobic Exercise + Venlafaxine XR (60-79 Years of Age) Venlafaxine XR Only (60-79 Years of Age) Aerobic Exercise + Venlafaxine XR (20-39 Years of Age) Venlafaxine XR Only (20-39 Years of Age)
    Arm/Group Description Venlafaxine (Effexor) Extended-Release (XR) comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Exercise will include walking on a treadmill 1 hour 3 times/week for 12 weeks. The intensity of the exercise will start at 50% of the age-based maximum for the first week and then increase and be maintained at 60-70% of the age-based maximum for the remainder of the intervention. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Venlafaxine (Effexor) XR comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Lorazepam: Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. Patients taking another benzodiazepine will be asked to convert from their current benzodiazepine to an equivalent dose of Lorazepam (2mg or less in 24 hours). This will be administered in pill form. Venlafaxine (Effexor) Extended-Release (XR) comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Exercise will include walking on a treadmill 1 hour 3 times/week for 12 weeks. The intensity of the exercise will start at 50% of the age-based maximum for the first week and then increase and be maintained at 60-70% of the age-based maximum for the remainder of the intervention. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Venlafaxine (Effexor) XR comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Lorazepam: Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. Patients taking another benzodiazepine will be asked to convert from their current benzodiazepine to an equivalent dose of Lorazepam (2mg or less in 24 hours). This will be administered in pill form.
    Measure Participants 2 3 4 3
    Count of Participants [Participants]
    NA
    NaN
    NA
    NaN
    NA
    NaN
    NA
    NaN
    3. Secondary Outcome
    Title Genetic Biomarkers
    Description Blood samples were collected to assess biomarkers, but funding is not yet available to perform analyses.
    Time Frame Baseline and 12 weeks

    Outcome Measure Data

    Analysis Population Description
    Blood samples were collected to assess biomarkers, but funding is not yet available to perform analyses.
    Arm/Group Title Aerobic Exercise + Venlafaxine XR (60-79 Years of Age) Venlafaxine XR Only (60-79 Years of Age) Aerobic Exercise + Venlafaxine XR (20-39 Years of Age) Venlafaxine XR Only (20-39 Years of Age)
    Arm/Group Description Venlafaxine (Effexor) Extended-Release (XR) comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Exercise will include walking on a treadmill 1 hour 3 times/week for 12 weeks. The intensity of the exercise will start at 50% of the age-based maximum for the first week and then increase and be maintained at 60-70% of the age-based maximum for the remainder of the intervention. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Venlafaxine (Effexor) XR comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Lorazepam: Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. Patients taking another benzodiazepine will be asked to convert from their current benzodiazepine to an equivalent dose of Lorazepam (2mg or less in 24 hours). This will be administered in pill form. Venlafaxine (Effexor) Extended-Release (XR) comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Exercise will include walking on a treadmill 1 hour 3 times/week for 12 weeks. The intensity of the exercise will start at 50% of the age-based maximum for the first week and then increase and be maintained at 60-70% of the age-based maximum for the remainder of the intervention. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Venlafaxine (Effexor) XR comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Lorazepam: Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. Patients taking another benzodiazepine will be asked to convert from their current benzodiazepine to an equivalent dose of Lorazepam (2mg or less in 24 hours). This will be administered in pill form.
    Measure Participants 2 3 4 3
    Count of Participants [Participants]
    NA
    NaN
    NA
    NaN
    NA
    NaN
    NA
    NaN
    4. Secondary Outcome
    Title Physical Activity (SenseWear Physical Activity-monitoring Armband)
    Description This will be used to acquire objective information about physical activity. This armband is worn around the upper arm (left triceps) for 1 week and collects information about skin temperature, galvanic skin response, heat flux, and motion via a 3-axis accelerometer. This information is used in an algorithm to determine energy expenditure (EE). The device has a resolution of 1-minute indicating that we can acquire the above information on a minute-by-minute basis, which will allow us to determine both duration and intensity of activity during a normal week. Higher values indicate higher levels of activity.
    Time Frame Baseline and 12 weeks

    Outcome Measure Data

    Analysis Population Description
    1 participant in the Venlafaxine XR Only (20-39 Years of Age) group was excluded from analyses as he/she was non-compliant with the medication regimen, discontinuing the medication after Week 8.
    Arm/Group Title Aerobic Exercise + Venlafaxine XR (60-79 Years of Age) Venlafaxine XR Only (60-79 Years of Age) Aerobic Exercise + Venlafaxine XR (20-39 Years of Age) Venlafaxine XR Only (20-39 Years of Age)
    Arm/Group Description Venlafaxine (Effexor) Extended-Release (XR) comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Exercise will include walking on a treadmill 1 hour 3 times/week for 12 weeks. The intensity of the exercise will start at 50% of the age-based maximum for the first week and then increase and be maintained at 60-70% of the age-based maximum for the remainder of the intervention. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Venlafaxine (Effexor) XR comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Venlafaxine (Effexor) Extended-Release (XR) comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Exercise will include walking on a treadmill 1 hour 3 times/week for 12 weeks. The intensity of the exercise will start at 50% of the age-based maximum for the first week and then increase and be maintained at 60-70% of the age-based maximum for the remainder of the intervention. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Venlafaxine (Effexor) XR comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours).
    Measure Participants 2 3 4 2
    Baseline Average Daily EE
    911.04
    (604.31)
    201.64
    (149.47)
    422.70
    (694.21)
    731.06
    (905.36)
    12 Week Average Daily EE
    324.03
    (352.57)
    212.48
    (216.95)
    694.21
    (455.45)
    905.36
    (596.69)
    5. Secondary Outcome
    Title Cardiovascular Fitness (Submaximal VO2)
    Description Cardiorespiratory fitness was measured via submaximal VO2 on a motorized treadmill while measuring oxygen utilization via Parvo Medics True one metabolic cart. The submaximal test followed a modified Balke protocol in which speed remained constant with the intensity being increased every two minutes via a raise of 2.0% of the incline. The speed was an agreed upon speed between participant and staff (between 2.0 and 4.0 mph). The submaximal VO2 was stopped when participant reached 85% of age predicted maximal heart rate (220 - age), rating of perceived exertion (RPE) equal to or greater than 15 for those who have blunted heart rate response due to beta block medication, or volitional termination by participant. Vital signs were monitored throughout the test and cool down period. Peak VO2 values for this cohort ranged from 14.04 to 36.48 ml/kg/min, with higher values correlated to higher fitness level.
    Time Frame Baseline and 12 weeks

    Outcome Measure Data

    Analysis Population Description
    1 participant in the "Venlafaxine XR Only (20-39 Years of Age)" group was excluded from analyses as he/she was non-compliant with the medication regimen, discontinuing the medication at Week 8.
    Arm/Group Title Aerobic Exercise + Venlafaxine XR (60-79 Years of Age) Venlafaxine XR Only (60-79 Years of Age) Aerobic Exercise + Venlafaxine XR (20-39 Years of Age) Venlafaxine XR Only (20-39 Years of Age)
    Arm/Group Description Venlafaxine (Effexor) Extended-Release (XR) comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Exercise will include walking on a treadmill 1 hour 3 times/week for 12 weeks. The intensity of the exercise will start at 50% of the age-based maximum for the first week and then increase and be maintained at 60-70% of the age-based maximum for the remainder of the intervention. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Venlafaxine (Effexor) XR comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Lorazepam: Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. Patients taking another benzodiazepine will be asked to convert from their current benzodiazepine to an equivalent dose of Lorazepam (2mg or less in 24 hours). This will be administered in pill form. Venlafaxine (Effexor) Extended-Release (XR) comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Exercise will include walking on a treadmill 1 hour 3 times/week for 12 weeks. The intensity of the exercise will start at 50% of the age-based maximum for the first week and then increase and be maintained at 60-70% of the age-based maximum for the remainder of the intervention. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Venlafaxine (Effexor) XR comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Lorazepam: Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. Patients taking another benzodiazepine will be asked to convert from their current benzodiazepine to an equivalent dose of Lorazepam (2mg or less in 24 hours). This will be administered in pill form.
    Measure Participants 2 3 4 2
    Baseline Submaximal VO2
    26.12
    (6.78)
    27.73
    (8.13)
    30.40
    (7.61)
    24.17
    (4.84)
    Week 12 Submaximal V02
    24.23
    (3.47)
    23.52
    (3.20)
    33.89
    (10.29)
    22.85
    (0.77)
    6. Secondary Outcome
    Title Functional Magnetic Resonance Imaging (fMRI)
    Description Brain imaging conducted with a 7 Tesla scanner. Of particular interest were changes in hippocampal volume, GABA, and glutamate. The changes regarding hippocampal volumes are reported below. This measurement is reported in mm^3, with higher numbers indicating higher levels of gray matter in the hippocampal region. Volume is combined between right and left hemispheres. GABA and glutamate are not reported. The method used to obtain the data was being piloted for this study, and due to methodological challenges, the data is not considered to be accurate and therefore cannot be analyzed/shared.
    Time Frame Baseline and 12 weeks

    Outcome Measure Data

    Analysis Population Description
    2 participants were excluded from analyses due to lack of usable data at both time points.
    Arm/Group Title Aerobic Exercise + Venlafaxine XR (60-79 Years of Age) Venlafaxine XR Only (60-79 Years of Age) Aerobic Exercise + Venlafaxine XR (20-39 Years of Age) Venlafaxine XR Only (20-39 Years of Age)
    Arm/Group Description Venlafaxine (Effexor) Extended-Release (XR) comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Exercise will include walking on a treadmill 1 hour 3 times/week for 12 weeks. The intensity of the exercise will start at 50% of the age-based maximum for the first week and then increase and be maintained at 60-70% of the age-based maximum for the remainder of the intervention. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Venlafaxine (Effexor) XR comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Lorazepam: Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. Patients taking another benzodiazepine will be asked to convert from their current benzodiazepine to an equivalent dose of Lorazepam (2mg or less in 24 hours). This will be administered in pill form. Venlafaxine (Effexor) Extended-Release (XR) comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Exercise will include walking on a treadmill 1 hour 3 times/week for 12 weeks. The intensity of the exercise will start at 50% of the age-based maximum for the first week and then increase and be maintained at 60-70% of the age-based maximum for the remainder of the intervention. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Venlafaxine (Effexor) XR comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Lorazepam: Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. Patients taking another benzodiazepine will be asked to convert from their current benzodiazepine to an equivalent dose of Lorazepam (2mg or less in 24 hours). This will be administered in pill form.
    Measure Participants 2 2 3 3
    Baseline Hippocampal Volume
    6703
    (839)
    6579
    (253)
    6192
    (1022)
    5652
    (902)
    Week 12 Hippocampal Volume
    6035
    (1850)
    6511
    (362)
    6040
    (894)
    6091
    (899)
    7. Secondary Outcome
    Title Neurocognitive Function (Neuropsychological Battery)
    Description The battery evaluates several cognitive domains. The Wechsler Adult Intelligence Scale, 4th ed. Digit Span subtest assesses attention and working memory. The Repeatable Battery of Neuropsychological Status (RBANS) measures Immediate and Delayed Memory, Attention, Language Abilities, and Visuospatial Functioning. Total index scores range from 40-155. The California Verbal Learning Test, 2nd Ed. (CVLT) assesses non-contextual verbal learning and memory. Z-scores are calculated for each of the constructs assessed by the CVLT. Subtests from the Deli-Kaplan Executive Function System (D-KEFS) assess aspects of executive functioning, including set-shifting (Trail Making Test Conditions 4 and 5: scaled score ranging from 0-19) and inhibition (Color-Word Interference Test Condition 3: weighted scaled score ranging from 1-19). Given that standardized scores are calculated for each of the neuropsychological measures, higher scores always indicate better cognitive functioning.
    Time Frame Baseline and 12 weeks

    Outcome Measure Data

    Analysis Population Description
    1 participant in the Venlafaxine XR Only (20-39 Years) group was excluded from analyses as he/she was non-compliant with the medication regimen. Another participant in the "Venlafaxine XR Only (60-79 Years of Age)" was excluded from analyses as he/she was unable to complete Week 12 testing due to physical limitations.
    Arm/Group Title Aerobic Exercise + Venlafaxine XR (60-79 Years of Age) Venlafaxine XR Only (60-79 Years of Age) Aerobic Exercise + Venlafaxine XR (20-39 Years of Age) Venlafaxine XR Only (20-39 Years of Age)
    Arm/Group Description Venlafaxine (Effexor) Extended-Release (XR) comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Exercise will include walking on a treadmill 1 hour 3 times/week for 12 weeks. The intensity of the exercise will start at 50% of the age-based maximum for the first week and then increase and be maintained at 60-70% of the age-based maximum for the remainder of the intervention. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Venlafaxine (Effexor) XR comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Venlafaxine (Effexor) Extended-Release (XR) comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Exercise will include walking on a treadmill 1 hour 3 times/week for 12 weeks. The intensity of the exercise will start at 50% of the age-based maximum for the first week and then increase and be maintained at 60-70% of the age-based maximum for the remainder of the intervention. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Venlafaxine (Effexor) XR comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours).
    Measure Participants 2 2 4 2
    Baseline RBANS Total Index Score
    77.00
    (0.00)
    96.00
    (19.80)
    101.00
    (13.78)
    80.00
    (7.07)
    Week 12 RBANS Total Index Score
    81.50
    (3.54)
    100.50
    (17.68)
    102.75
    (19.74)
    85.50
    (7.78)
    Baseline CVLT Long Delay Free Recall
    6.50
    (7.78)
    10.00
    (8.49)
    12.00
    (4.55)
    8.50
    (2.12)
    Week 12 CVLT Long Delay Free Recall
    3.00
    (4.24)
    12.50
    (3.54)
    13.50
    (3.00)
    7.50
    (2.12)
    Baseline DKEFS Trailmaking
    10.00
    (0.00)
    11.00
    (1.41)
    9.50
    (1.29)
    4.50
    (2.12)
    Week 12 DKEFS Trailmaking
    5.50
    (3.54)
    10.50
    (0.71)
    10.00
    (1.41)
    5.50
    (3.54)
    Baseline Digit Span Forward
    7.00
    (1.41)
    7.50
    (0.71)
    11.75
    (2.22)
    10.00
    (1.41)
    Week 12 Digit Span Forward
    7.00
    (1.41)
    9.00
    (1.41)
    12.00
    (1.41)
    8.50
    (2.12)
    Baseline Digit Span Backwards
    7.00
    (2.83)
    7.00
    (1.41)
    9.75
    (1.71)
    7.00
    (1.41)
    Week 12 Digit Span Backwards
    7.50
    (2.12)
    8.50
    (0.71)
    9.00
    (1.83)
    6.50
    (0.71)
    Baseline Color Word Interference Condition 3
    9.00
    (5.66)
    10.00
    (1.41)
    11.25
    (2.87)
    7.50
    (0.71)
    Week 12 Color Word Interference Condition 3
    7.50
    (4.95)
    10.50
    (0.71)
    9.75
    (4.72)
    10.00
    (2.83)

    Adverse Events

    Time Frame 12 weeks
    Adverse Event Reporting Description
    Arm/Group Title Aerobic Exercise + Venlafaxine XR (60-79 Years of Age) Venlafaxine XR Only (60-79 Years of Age) Aerobic Exercise + Venlafaxine XR (20-39 Years of Age) Venlafaxine XR Only (20-39 Years of Age)
    Arm/Group Description Venlafaxine (Effexor) Extended-Release (XR) comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Exercise will include walking on a treadmill 1 hour 3 times/week for 12 weeks. The intensity of the exercise will start at 50% of the age-based maximum for the first week and then increase and be maintained at 60-70% of the age-based maximum for the remainder of the intervention. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Venlafaxine (Effexor) XR comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Lorazepam: Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. Patients taking another benzodiazepine will be asked to convert from their current benzodiazepine to an equivalent dose of Lorazepam (2mg or less in 24 hours). This will be administered in pill form. Venlafaxine (Effexor) Extended-Release (XR) comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Exercise will include walking on a treadmill 1 hour 3 times/week for 12 weeks. The intensity of the exercise will start at 50% of the age-based maximum for the first week and then increase and be maintained at 60-70% of the age-based maximum for the remainder of the intervention. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Venlafaxine (Effexor) XR comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours). Lorazepam: Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. Patients taking another benzodiazepine will be asked to convert from their current benzodiazepine to an equivalent dose of Lorazepam (2mg or less in 24 hours). This will be administered in pill form.
    All Cause Mortality
    Aerobic Exercise + Venlafaxine XR (60-79 Years of Age) Venlafaxine XR Only (60-79 Years of Age) Aerobic Exercise + Venlafaxine XR (20-39 Years of Age) Venlafaxine XR Only (20-39 Years of Age)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%)
    Serious Adverse Events
    Aerobic Exercise + Venlafaxine XR (60-79 Years of Age) Venlafaxine XR Only (60-79 Years of Age) Aerobic Exercise + Venlafaxine XR (20-39 Years of Age) Venlafaxine XR Only (20-39 Years of Age)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/4 (0%)
    Other (Not Including Serious) Adverse Events
    Aerobic Exercise + Venlafaxine XR (60-79 Years of Age) Venlafaxine XR Only (60-79 Years of Age) Aerobic Exercise + Venlafaxine XR (20-39 Years of Age) Venlafaxine XR Only (20-39 Years of Age)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/2 (50%) 3/3 (100%) 4/4 (100%) 4/4 (100%)
    Cardiac disorders
    Palpitations 0/2 (0%) 1/3 (33.3%) 0/4 (0%) 0/4 (0%)
    Eye disorders
    Blurred vision 0/2 (0%) 1/3 (33.3%) 1/4 (25%) 1/4 (25%)
    Gastrointestinal disorders
    Constipation 1/2 (50%) 2/3 (66.7%) 2/4 (50%) 2/4 (50%)
    Diarrhea 0/2 (0%) 0/3 (0%) 2/4 (50%) 0/4 (0%)
    Nausea/Vomiting 1/2 (50%) 2/3 (66.7%) 1/4 (25%) 1/4 (25%)
    Bloatedness 0/2 (0%) 0/3 (0%) 1/4 (25%) 0/4 (0%)
    General disorders
    Dry mouth 1/2 (50%) 3/3 (100%) 2/4 (50%) 2/4 (50%)
    Drowsiness 0/2 (0%) 1/3 (33.3%) 2/4 (50%) 2/4 (50%)
    Increased appetite 0/2 (0%) 1/3 (33.3%) 0/4 (0%) 0/4 (0%)
    Decreased appetite 0/2 (0%) 1/3 (33.3%) 2/4 (50%) 2/4 (50%)
    Feeling light-headed on standing 0/2 (0%) 3/3 (100%) 1/4 (25%) 0/4 (0%)
    Feeling like the room is spinning 0/2 (0%) 0/3 (0%) 1/4 (25%) 0/4 (0%)
    Sweating 0/2 (0%) 2/3 (66.7%) 3/4 (75%) 2/4 (50%)
    Increased Body Temperature 0/2 (0%) 2/3 (66.7%) 2/4 (50%) 1/4 (25%)
    Tremor 0/2 (0%) 1/3 (33.3%) 1/4 (25%) 0/4 (0%)
    Disorientation 0/2 (0%) 1/3 (33.3%) 0/4 (0%) 0/4 (0%)
    Yawning 1/2 (50%) 2/3 (66.7%) 0/4 (0%) 1/4 (25%)
    Stiff Neck 0/2 (0%) 1/3 (33.3%) 0/4 (0%) 0/4 (0%)
    Agitation 0/2 (0%) 0/3 (0%) 1/4 (25%) 0/4 (0%)
    Jaw pain 0/2 (0%) 0/3 (0%) 1/4 (25%) 0/4 (0%)
    Metabolism and nutrition disorders
    Weight Gain 0/2 (0%) 1/3 (33.3%) 0/4 (0%) 0/4 (0%)
    Nervous system disorders
    Headache 0/2 (0%) 2/3 (66.7%) 2/4 (50%) 2/4 (50%)
    Psychiatric disorders
    Insomnia 0/2 (0%) 0/3 (0%) 2/4 (50%) 0/4 (0%)
    Renal and urinary disorders
    Problems with urination 0/2 (0%) 0/3 (0%) 0/4 (0%) 1/4 (25%)
    Reproductive system and breast disorders
    Problems with Sexual Function 0/2 (0%) 0/3 (0%) 0/4 (0%) 1/4 (25%)
    Skin and subcutaneous tissue disorders
    Acne 0/2 (0%) 0/3 (0%) 0/4 (0%) 1/4 (25%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT 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 Dr. Kirk Erickson
    Organization University of Pittsburgh
    Phone 412-624-4533
    Email kiericks@pitt.edu
    Responsible Party:
    Kirk Erickson, PhD, Associate Professor/Principal Investigator, University of Pittsburgh
    ClinicalTrials.gov Identifier:
    NCT02407704
    Other Study ID Numbers:
    • MH090333-04
    • PRO13110090
    • MH090333
    First Posted:
    Apr 3, 2015
    Last Update Posted:
    May 23, 2018
    Last Verified:
    Apr 1, 2018