Shoulder Pain
Conditions
Keywords
Personalized Pharmaceutical, Personalized Education
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.
Interventions
DRUGPropranolol 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.
DRUGPlacebo
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.
BEHAVIORALShoulder 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.
BEHAVIORALPain 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.
Sponsors
National Institutes of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
Periodic screenings of volunteers were completed on the University of Florida campus and in the local community. All participants provided informed consent to screening. Participants who screened as being in the high-risk subgroup and appropriate for exercise-induced muscle injury were eligible for participation in the clinical trial and provided additional informed consent.
Pre-assignment details
Participants who were eligible based on being in the high-risk subgroup and appropriate for exercise-induced muscle injury were required to take additional testing to determine the appropriateness of receiving propranolol and also identifying other medical reasons for exclusion. 3 enrolled participants were excluded/withdrawn pre-randomization.
Participants by arm
| Arm | Count |
|---|---|
| Personalized Pharmaceutical and Education (C) 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.
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.
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. | 62 |
| Placebo Pharmaceutical, General Education (B) This group will have the placebo pharmaceutical administered orally and receive general shoulder anatomy education modules as the interventions for this arm.
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.
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. | 57 |
| Placebo Pharmaceutical, Personalized Education (A) This group will have the placebo pharmaceutical administered orally and receive the pain processing education modules as the combined intervention for this arm.
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.
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. | 57 |
| Personalized Pharmaceutical, General Education (D) This group will have propranolol (Propranolol LA) 60 mg administered orally and receive general shoulder anatomy education modules as the interventions for this arm.
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.
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. | 57 |
| Total | 233 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Personalized Pharmaceutical and Education (C) | Placebo Pharmaceutical, General Education (B) | Placebo Pharmaceutical, Personalized Education (A) | Personalized Pharmaceutical, General Education (D) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 21.4 years STANDARD_DEVIATION 5.3 | 20.3 years STANDARD_DEVIATION 2.5 | 21.7 years STANDARD_DEVIATION 5.9 | 20.5 years STANDARD_DEVIATION 1.9 | 21.0 years STANDARD_DEVIATION 4.3 |
| Body Mass Index (BMI) | 23.6 kg/m^2 STANDARD_DEVIATION 4.4 | 23.9 kg/m^2 STANDARD_DEVIATION 4.1 | 24.1 kg/m^2 STANDARD_DEVIATION 4.5 | 23.4 kg/m^2 STANDARD_DEVIATION 4.3 | 23.7 kg/m^2 STANDARD_DEVIATION 4.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants | 14 Participants | 19 Participants | 21 Participants | 77 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 43 Participants | 38 Participants | 36 Participants | 156 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Fear of Pain Questionnaire (FPQ) | 14.5 units on a scale STANDARD_DEVIATION 6 | 14.6 units on a scale STANDARD_DEVIATION 7 | 15.6 units on a scale STANDARD_DEVIATION 6.8 | 14.5 units on a scale STANDARD_DEVIATION 5.5 | 14.8 units on a scale STANDARD_DEVIATION 6.3 |
| Pain Catastrophizing Scale (PCS) | 12.6 units on a scale STANDARD_DEVIATION 9.1 | 12.6 units on a scale STANDARD_DEVIATION 7.2 | 12.7 units on a scale STANDARD_DEVIATION 9 | 11.4 units on a scale STANDARD_DEVIATION 7.8 | 12.3 units on a scale STANDARD_DEVIATION 8.3 |
| Patient Health Questionnaire-9 (PHQ-9) | 1.9 units on a scale STANDARD_DEVIATION 2.3 | 2.8 units on a scale STANDARD_DEVIATION 3.1 | 3.2 units on a scale STANDARD_DEVIATION 4.4 | 2.9 units on a scale STANDARD_DEVIATION 3.8 | 2.7 units on a scale STANDARD_DEVIATION 3.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 15 Participants | 20 Participants | 18 Participants | 18 Participants | 71 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 15 Participants | 13 Participants | 7 Participants | 45 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 2 Participants | 0 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) White | 33 Participants | 20 Participants | 24 Participants | 31 Participants | 108 Participants |
| Region of Enrollment United States | 62 Participants | 57 Participants | 57 Participants | 57 Participants | 233 Participants |
| Sex: Female, Male Female | 40 Participants | 37 Participants | 39 Participants | 37 Participants | 153 Participants |
| Sex: Female, Male Male | 22 Participants | 20 Participants | 18 Participants | 20 Participants | 80 Participants |
| Tampa Scale for Kinesiophobia-11 (TSK-11) | 19.6 units on a scale STANDARD_DEVIATION 4.7 | 19.5 units on a scale STANDARD_DEVIATION 5 | 19.4 units on a scale STANDARD_DEVIATION 5.7 | 19.8 units on a scale STANDARD_DEVIATION 5.2 | 19.5 units on a scale STANDARD_DEVIATION 5.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 62 | 0 / 57 | 0 / 57 | 0 / 57 |
| other Total, other adverse events | 49 / 62 | 43 / 57 | 39 / 57 | 43 / 57 |
| serious Total, serious adverse events | 0 / 62 | 0 / 57 | 0 / 57 | 0 / 57 |
Outcome results
Primary
Number of Participants Who Met the Recovery Criterion for Shoulder Pain Intensity
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.
Time frame: Approximately 6 days
Population: Analysis Population consists of 233 participants. 28 out of 261 randomized participants were excluded due to criteria related to the safety of propranolol administration (eg, abnormal ECG findings) or a candidate not being able to complete the study (eg, change in time commitment). These post-randomization exclusions were made for safety reasons and participants were excluded prior to any baseline data collection, induction of exercise-induced muscle injury, and treatment allocation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Personalized Pharmaceutical and Education (C) | Number of Participants Who Met the Recovery Criterion for Shoulder Pain Intensity | 39 Participants |
| Placebo Pharmaceutical, General Education (B) | Number of Participants Who Met the Recovery Criterion for Shoulder Pain Intensity | 32 Participants |
| Placebo Pharmaceutical, Personalized Education (A) | Number of Participants Who Met the Recovery Criterion for Shoulder Pain Intensity | 32 Participants |
| Personalized Pharmaceutical, General Education (D) | Number of Participants Who Met the Recovery Criterion for Shoulder Pain Intensity | 32 Participants |
Secondary
Brief Pain Inventory (BPI) for Pain Duration
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.
Time frame: Daily until recovery criterion met, approximately 5-15 days
Population: Analysis Population consists of 233 participants. 28 out of 261 randomized participants were excluded due to criteria related to the safety of propranolol administration (eg, abnormal ECG findings) or a candidate not being able to complete the study (eg, change in time commitment). These post-randomization exclusions were made for safety reasons and participants were excluded prior to any baseline data collection, induction of exercise-induced muscle injury, and treatment allocation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Personalized Pharmaceutical and Education (C) | Brief Pain Inventory (BPI) for Pain Duration | 4 days |
| Placebo Pharmaceutical, General Education (B) | Brief Pain Inventory (BPI) for Pain Duration | 4 days |
| Placebo Pharmaceutical, Personalized Education (A) | Brief Pain Inventory (BPI) for Pain Duration | 4 days |
| Personalized Pharmaceutical, General Education (D) | Brief Pain Inventory (BPI) for Pain Duration | 4 days |
Secondary
Brief Pain Inventory (BPI) for Worst Shoulder Pain Intensity (Highest Daily Pain Intensity Rating) Recorded During Recovery.
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.
Time frame: Day 2 value of the worst pain intensity is reported
Population: Analysis Population consists of 233 participants. 28 out of 261 randomized participants were excluded due to criteria related to the safety of propranolol administration (eg, abnormal ECG findings) or a candidate not being able to complete the study (eg, change in time commitment). These post-randomization exclusions were made for safety reasons and participants were excluded prior to any baseline data collection, induction of exercise-induced muscle injury, and treatment allocation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Personalized Pharmaceutical and Education (C) | Brief Pain Inventory (BPI) for Worst Shoulder Pain Intensity (Highest Daily Pain Intensity Rating) Recorded During Recovery. | 2.9 score on a scale | Standard Deviation 1.9 |
| Placebo Pharmaceutical, General Education (B) | Brief Pain Inventory (BPI) for Worst Shoulder Pain Intensity (Highest Daily Pain Intensity Rating) Recorded During Recovery. | 3.2 score on a scale | Standard Deviation 2.1 |
| Placebo Pharmaceutical, Personalized Education (A) | Brief Pain Inventory (BPI) for Worst Shoulder Pain Intensity (Highest Daily Pain Intensity Rating) Recorded During Recovery. | 2.9 score on a scale | Standard Deviation 2.1 |
| Personalized Pharmaceutical, General Education (D) | Brief Pain Inventory (BPI) for Worst Shoulder Pain Intensity (Highest Daily Pain Intensity Rating) Recorded During Recovery. | 3.1 score on a scale | Standard Deviation 2 |
Secondary
Disabilities of the Arm, Shoulder, and Hand Questionnaire (DASH)
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.
Time frame: Daily until recovery criterion met, approximately 5-15 days
Population: Analysis Population consists of 233 participants. 28 out of 261 randomized participants were excluded due to criteria related to the safety of propranolol administration (eg, abnormal ECG findings) or a candidate not being able to complete the study (eg, change in time commitment). These post-randomization exclusions were made for safety reasons and participants were excluded prior to any baseline data collection, induction of exercise-induced muscle injury, and treatment allocation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Personalized Pharmaceutical and Education (C) | Disabilities of the Arm, Shoulder, and Hand Questionnaire (DASH) | 8.2 score on a scale | Standard Deviation 8.5 |
| Placebo Pharmaceutical, General Education (B) | Disabilities of the Arm, Shoulder, and Hand Questionnaire (DASH) | 10.5 score on a scale | Standard Deviation 12.4 |
| Placebo Pharmaceutical, Personalized Education (A) | Disabilities of the Arm, Shoulder, and Hand Questionnaire (DASH) | 11.4 score on a scale | Standard Deviation 12.9 |
| Personalized Pharmaceutical, General Education (D) | Disabilities of the Arm, Shoulder, and Hand Questionnaire (DASH) | 9.4 score on a scale | Standard Deviation 8.3 |