Biopsychosocial Influence on Shoulder Pain

Phase 2

Completed

Conditions: Shoulder Pain

Interventions: Drug: Placebo
Drug: Propranolol LA (60 mg)
Behavioral: Pain Processing Education
Behavioral: Shoulder Anatomy Education

Registration Number: NCT02620579

Lead Sponsor: Duke University

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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 264

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Personalized Pharmaceutical and Education	Pain Processing 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.
Placebo Pharmaceutical, General Education	Placebo	This group will have the placebo pharmaceutical administered orally and receive general shoulder anatomy education modules as the interventions for this arm.
Placebo Pharmaceutical, General Education	Shoulder Anatomy Education	This group will have the placebo pharmaceutical administered orally and receive general shoulder anatomy education modules as the interventions for this arm.
Placebo Pharmaceutical, Personalized Education	Placebo	This group will have the placebo pharmaceutical administered orally and receive the pain processing education modules as the combined intervention for this arm.
Placebo Pharmaceutical, Personalized Education	Pain Processing Education	This group will have the placebo pharmaceutical administered orally and receive the pain processing education modules as the combined intervention for this arm.
Personalized Pharmaceutical, General Education	Propranolol LA (60 mg)	This group will have propranolol (Propranolol LA) 60 mg administered orally and receive general shoulder anatomy education modules as the interventions for this arm.
Personalized Pharmaceutical, General Education	Shoulder Anatomy 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.
Personalized Pharmaceutical and Education	Propranolol LA (60 mg)	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Met the Recovery Criterion for Shoulder Pain Intensity	Approximately 6 days	The outcome has a range between 0 and 1, the higher scores mean a better outcome. Successful recovery was determined based on meeting the recovery criterion for shoulder pain intensity by at least 6 days. Specifically, recovery (Yes or No) was defined using Brief Pain Inventory (BPI) ratings as a current pain intensity rating of 0/10 and a worst pain intensity rating of less than 2/10.

Secondary Outcome Measures

Name	Time	Method
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). BPI 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. The pain duration is number of days from the date of induced pain to date of recovery. The longer the duration means a worse outcome.
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 Worst Shoulder Pain Intensity (Highest Daily Pain Intensity Rating) Recorded During Recovery.	Day 2 value of the worst pain intensity is reported	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 worst pain intensity rating at Day 2 (when participants usually had the Peak Shoulder Pain Intensity) is reported.