BISP: Biopsychosocial Influence on Shoulder Pain
Study Details
Study Description
Brief Summary
Chronic shoulder pain is a common, costly, and disabling problem for society. The identification of factors predictive of the development of chronic shoulder pain is necessary to develop innovative and effective treatments to reduce the societal impact of shoulder disorders. In previous work the investigators identified a genetic and psychological subgroup that robustly predicted heightened shoulder pain responses in a pre-clinical cohort and poor 12 month shoulder pain recovery rates in a clinical surgical cohort. In this follow-up study the investigator proposes to test how interventions tailored to the high risk subgroup affect pain responses in a pre-clinical cohort.
The optimal theorized match for the identified high-risk subgroup is a combination of personalized pharmaceutical and education interventions. This combined personalized intervention versus a placebo pharmaceutical and general education intervention group is the primary comparison of interest. Also, an evaluation of the individual effect of personalized pharmaceutical and educational interventions will be part of the study. Such comparisons will provide important information on what the active portion of the combined personalized intervention may be.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Potential subjects will be screened and those meeting the high-risk criteria based on COMT genotype for high pain sensitivity and pain catastrophizing questionnaire score will be eligible for randomization into intervention groups (stratified by sex). Exercise induced shoulder injury will serve as the pain generating mechanism on Day 1 and participants will receive pharmaceutical and education interventions over Days 1-4, and Days 2-4 respectively. Statistical analysis will determine whether the combined personalized intervention group experienced shorter shoulder pain duration, lower peak pain intensity, or decreased upper-extremity disability and determine which molecular, psychological, and pain sensitivity regulation mechanisms are associated with pain relief. A preliminary analysis is planned after the first 300 subjects are equally randomized to the 4 intervention groups. The comparison of interest for the preliminary analysis is the combined personalized intervention group with the placebo and general education group for the primary outcome. Depending on the results of this preliminary analysis the randomization pattern may change, with details of these changes available in the protocol paper.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Personalized Pharmaceutical and Education This group will have propranolol (Propranolol LA) 60 mg administered orally and receive the pain processing education modules as the combined intervention for this arm. |
Drug: Propranolol LA (60 mg)
Long-acting propranolol (Propranolol LA) 60 mg to be administered orally daily for Days 1 (before exercise induced muscle injury) and Days 2-4 following exercise induced muscle injury.
Other Names:
Behavioral: Pain Processing Education
Pain processing education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of better understanding of pain processing and psycho-education. This information will encourage shoulder activation by: a) reducing the threat of muscle injury; b) encouraging normal use of the shoulder and arm; and c) addressing specific concerns expressed by the subject (e.g. pain with shoulder motion is a sign of re-injury). This education component will be devoid of detailed information on shoulder anatomy, movement, and injury that characterizes the Shoulder Anatomy Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.
Other Names:
|
| Placebo Comparator: Placebo Pharmaceutical, General Education This group will have the placebo pharmaceutical administered orally and receive general shoulder anatomy education modules as the interventions for this arm. |
Drug: Placebo
Placebo capsules will be prepared by the University of Florida Investigational Drug Service to be visually indistinguishable from the active medication and delivered orally. Placebo administration will be done in the same fashion as propranolol - administered on Days 1 (before exercise induced muscle injury) and the Days 2-4 after the exercise induced muscle injury.
Other Names:
Behavioral: Shoulder Anatomy Education
Shoulder anatomy education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of participant understanding shoulder anatomy and injury while reviewing: a) structure and arthrokinematics of the shoulder joint; b) muscle anatomy of the shoulder with emphasis on the rotator cuff; and c) potential shoulder pain generators from the exercise-induced injury. This education component will be devoid of information related to pain signaling and cognitive restructuring that characterizes Pain Processing Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.
Other Names:
|
| Active Comparator: Placebo Pharmaceutical, Personalized Education This group will have the placebo pharmaceutical administered orally and receive the pain processing education modules as the combined intervention for this arm. |
Drug: Placebo
Placebo capsules will be prepared by the University of Florida Investigational Drug Service to be visually indistinguishable from the active medication and delivered orally. Placebo administration will be done in the same fashion as propranolol - administered on Days 1 (before exercise induced muscle injury) and the Days 2-4 after the exercise induced muscle injury.
Other Names:
Behavioral: Pain Processing Education
Pain processing education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of better understanding of pain processing and psycho-education. This information will encourage shoulder activation by: a) reducing the threat of muscle injury; b) encouraging normal use of the shoulder and arm; and c) addressing specific concerns expressed by the subject (e.g. pain with shoulder motion is a sign of re-injury). This education component will be devoid of detailed information on shoulder anatomy, movement, and injury that characterizes the Shoulder Anatomy Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.
Other Names:
|
| Active Comparator: Personalized Pharmaceutical, General Education This group will have propranolol (Propranolol LA) 60 mg administered orally and receive general shoulder anatomy education modules as the interventions for this arm. |
Drug: Propranolol LA (60 mg)
Long-acting propranolol (Propranolol LA) 60 mg to be administered orally daily for Days 1 (before exercise induced muscle injury) and Days 2-4 following exercise induced muscle injury.
Other Names:
Behavioral: Shoulder Anatomy Education
Shoulder anatomy education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of participant understanding shoulder anatomy and injury while reviewing: a) structure and arthrokinematics of the shoulder joint; b) muscle anatomy of the shoulder with emphasis on the rotator cuff; and c) potential shoulder pain generators from the exercise-induced injury. This education component will be devoid of information related to pain signaling and cognitive restructuring that characterizes Pain Processing Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Brief Pain Inventory (BPI) for pain duration [Daily until recovery criterion met, approximately 5-15 days]
The Brief Pain Inventory (BPI) consists of rating pain intensity on an 11-point numerical rating scale ranging from 0 (no pain) to 10 (worst pain intensity imaginable). This measure will be recorded daily and the recovery criterion used for this study will be a BPI rating of current pain 0/10 and worst pain rating of less than 2/10.
- Disabilities of the Arm, Shoulder, and Hand Questionnaire (DASH) [Daily until recovery criterion met, approximately 5-15 days]
The abridged version of the DASH (the QuickDASH) which consists of 11 functional items, with total scores ranging from 0 (not disability) to 100 (complete disability) will be used to assess upper-extremity disability. The primary outcome will be the highest DASH score recorded during the pain intensity recovery period.
- Brief Pain Inventory (BPI) for peak shoulder pain intensity (highest daily pain intensity rating) recorded during recovery. [Daily until recovery criterion met, approximately 5-15 days]
The Brief Pain Inventory (BPI) which consists of rating pain intensity on an 11-point numerical rating scale ranging from 0 (no pain) to 10 (worst pain intensity imaginable). Participants will rate their current, best, and worst pain intensity on the BPI. This measure will be recorded daily through study completion, an average of 5 days. The highest pain intensity rating during that time period will be recorded as the Peak Shoulder Pain Intensity.
Secondary Outcome Measures
- Pain Catastrophizing Scale (PCS) [Daily for 5 days]
The PCS is a 13-item instrument which instruction participants to reflect on past painful experiences, and to indicate the degree to which they experienced each of 13 thoughts or feelings when experiencing pain, on 5-point scales with the end points (0) not at all and (4) all the time. The PCS yields a total score and three subscale scores assessing rumination, magnification and helplessness. The PCS total score is computed by summing responses to all 13 items. PCS total scores range from 0 - 52. The PCS subscales are computed by summing the responses to the following items: Rumination: Sum of items 8, 9, 10, 11 Magnification: Sum of items 6, 7, 13 Helplessness: Sum of items 1, 2, 3, 4, 5, 12
- Tampa Scale of Kinesiophobia (TSK-11) [Daily for 5 days]
The TSK-11 is a 11-item self report checklist using a 4-point Likert scale that was developed as a measure of fear of movement or (re)injury. The total score ranges between 11 and 44. A higher value on the TSK indicates a high degree of kinesiophobia.
- Fear of Pain Questionnaire (FPQ) [Daily for 5 days]
The Fear of Pain Questionnaire (FPQ) is a self-report measure of pain-related fear containing 3 subscales. We will be using a shortened 9 item version in this study. Participants rate their anticipation of fear on a 5-point Likert scale ranging from 1 (not at all) to 5 (extreme). The 3 FPQ subscales are summed to create one total score. Higher scores indicate a greater pain-related fear and the lower scores indicate a lesser degree of fear. The overall scores range from 9 - 45.
- Suprathreshold heat pain responses [Daily for 5 days]
Suprathreshold heat pain response measures will be completed using the Pathway ATS/CHEPS Model (Medoc, Durham NC) unit or the TSA Neurosensory Analyzer (Medoc, Durham NC). The pain responses will be acquired with a VAS response to each stimulus. The VAS will consist of a 10 cm line whose endpoints are designated as 'no pain sensation' and 'the most intense pain sensation imaginable'. Stimuli will be applied to both arms.
- Pressure pain threshold [Daily for 5 days]
Pressure pain threshold response measures are done using a pressure algometer. A research assistant will apply pressure at 1kg/second through a application tip at the following anatomical locations: deltoid (local) and tibialis anterior (remote). The pressure pain sensitivity will be determined by recording the kg/cm2 when pain is first reported at each location. Trials will be repeated to ensure consistency.
- Conditioned pain modulation [Daily for 5 days]
The conditioning stimulus will be cold water applied to the right arm for up to 60 seconds, and the testing stimulus will be pressure applied to the tibialis anterior opposite the side of fatigue.
- Molecular and inflammatory measures [Daily for 5 days]
These measures will capture relevant inflammatory biomarkers. Thus, we plan to perform assays for IL1B, IL6, IL8, and TNFα at baseline, immediately after the exercise-induced injury, and at regular daily intervals. Additional inflammatory or pain regulatory markers may be assessed depending on updates from other ongoing studies.
Eligibility Criteria
Criteria
Inclusion Criteria:
- English speaking
Exclusion Criteria:
-
chronic pain (> 3 months) in any area,
-
currently experiencing neck or shoulder pain,
-
previous history of neck or shoulder pain (operationally defined as experiencing neck or shoulder pain for longer than 48 hours or seeking medical treatment for neck or shoulder pain),
-
neurological impairment of the in the upper-extremity (determined by loss of sensation, muscle weakness, and reflex changes),
-
regular participation in upper-extremity weight training,
-
currently or regular use of pain medication, and
-
previous history of upper-extremity surgery.
Additional exclusion criteria for propranolol administration are reported history of or presence of any of the following cardiovascular conditions:
-
clinically significant abnormal 12-lead ECG,
-
sinus bradycardia (resting heart rate below 55 beats per minute),
-
greater than first degree heart block,
-
cardiac failure,
-
coronary artery disease,
-
uncontrolled hypertension (resting systolic blood pressure above 140 mm Hg), or hypotension (resting systolic blood pressure below 90 mm Hg),
-
Wolff-Parkinson-White syndrome.
Non-cardiovascular reasons for study exclusion include:
-
bronchial asthma,
-
nonallergic bronchospasm,
-
history of recent major surgery requiring general anesthesia,
-
diabetes,
-
pregnancy,
-
major depression.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Florida Clinical and Translational Science Institute | Gainesville | Florida | United States | 32610 |
Sponsors and Collaborators
- Duke University
- National Institutes of Health (NIH)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Investigators
- Principal Investigator: Mark Bishop, PhD, University of Florida
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Borsa PA, Parr JJ, Wallace MR, Wu SS, Dai Y, Fillingim RB, George SZ. Genetic and psychological factors interact to predict physical impairment phenotypes following exercise-induced shoulder injury. J Pain Res. 2018 Oct 23;11:2497-2508. doi: 10.2147/JPR.S171498. eCollection 2018.
- Butera KA, George SZ, Borsa PA, Dover GC. Prolonged Reduction in Shoulder Strength after Transcutaneous Electrical Nerve Stimulation Treatment of Exercise-Induced Acute Muscle Pain. Pain Pract. 2018 Nov;18(8):954-968. doi: 10.1111/papr.12690. Epub 2018 Apr 6.
- George SZ, Staud R, Borsa PA, Wu SS, Wallace MR, Greenfield WH, Mackie LN, Fillingim RB. Biopsychosocial influence on shoulder pain: Rationale and protocol for a pre-clinical trial. Contemp Clin Trials. 2017 May;56:9-17. doi: 10.1016/j.cct.2017.03.005. Epub 2017 Mar 14.
- Pro00078287
- 2R01AR055899