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Sex Hormone Supplementation and Rotator Cuff Repair: A Preliminary Randomized Trial

Phase 2
Recruiting
Conditions
Rotator Cuff Tears
Interventions
Procedure: Rotator Cuff Repair
Registration Number
NCT04944836
Lead Sponsor
University of Utah
Brief Summary

Shoulder tendon tears are a common cause of shoulder pain and disability and after surgery the repaired tendon often does not heal. In this pilot study, men with low sex hormone levels will be randomly assigned to receive sex hormone therapy or placebo pills while healing from tendon repair surgery in their shoulder. Sex hormone therapy increases sex hormone levels, and the investigators will test whether these increased sex hormone levels show promise in improving tendon healing and patient shoulder function and pain.

Detailed Description

The rotator cuff is a system of tendons in the shoulder that stabilize the ball within the socket. These tendons frequently tear with age, which causes pain, weakness, and dysfunction in the shoulder. While these tears can be surgically repaired, they do not always heal. Our data suggest that deficiency of testosterone and estrogen can contribute to both tearing of the rotator cuff and failure of healing after rotator cuff repair. Testosterone can be converted into estrogen in the body through the aromatase enzyme, which is in both tendons and bones, as well as other tissues. Both testosterone and estrogen can improve bone quality. While testosterone is frequently prescribed for testosterone deficiency, when it is given your body no longer has the drive to make testosterone. So when the treatment is withdrawn testosterone levels can go very low until feedback mechanisms in the body motivate it to make more. As a result, testosterone is not usually given temporarily. For temporary treatment clomiphene avoids this issue. Clomiphene works at the feedback mechanisms within the body to trick the body into thinking testosterone and estrogen levels are low and thus to motivate it to make more testosterone and estrogen. However, clomiphene can only be given continuously to men, because women's estrogen levels regularly cycle up and down on a monthly basis and clomiphene interferes with this cycle. The purpose of this study is to determine whether clomiphene treatment decreases pain and improves function, increases tendon healing, and improves bone quality with rotator cuff repair in men. We hypothesize that clomiphene treatment will decrease pain and improve function, improve tendon healing, and improve bone quality with rotator cuff repair in men. This is a placebo-controlled study, so a control group of patients will received placebo pills, i.e. "sugar pills", instead of clomiphene. This is a randomized study, so patients enrolled in the study will be randomly assigned to the clomiphene group or the placebo group. This is a blinded study, so both the patients enrolled in the will not know whether they are in the clomiphene or the control group. This is a double-blinded study, so the doctors performing the surgeries and the study will not know whether each specific patient is in the clomiphene or the control group. Study participants will first start the clomiphene treatment one month before surgery and will continue the treatment for six months after surgery. Both before surgery and six months after surgery, study participants will fill out study questionnaires about shoulder pain and function. Both before surgery and six months after surgery, study participants will undergo an magnetic resonance imaging study to examine the rotator cuff tendons as well as the bone quality within the shoulder. The magnetic resonance imaging study after surgery is provided free to study participants. Study participants will be compensated for completing the study. These results are important because may lead to a better understanding of the problem, more effective treatment, and improved clinical outcomes for future patients.

Recruitment & Eligibility

Status
RECRUITING
Sex
Male
Target Recruitment
58
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ControlRotator Cuff RepairAll patients will receive non-labeled pills identical in appearance from our pharmacy, to be taking once every other day. In the control group, these will be placebo. These will be taken every other day for seven months beginning four week prior to surgery and extending for six months after surgery.
ClomipheneRotator Cuff RepairAll patients will receive non-labeled pills identical in appearance from our pharmacy, to be taking once every other day. In the study group, these will contain 50 mg of clomiphene citrate. These will be taken every other day for seven months beginning four week prior to surgery and extending for six months after surgery.
ClomipheneClomiphene CitrateAll patients will receive non-labeled pills identical in appearance from our pharmacy, to be taking once every other day. In the study group, these will contain 50 mg of clomiphene citrate. These will be taken every other day for seven months beginning four week prior to surgery and extending for six months after surgery.
Primary Outcome Measures
NameTimeMethod
Magnetic Resonance Imaging (MRI) tendon healing Post-opTo be collected at 6 months (±4 weeks) post-operatively.

MRI scans will be assessed by observers blinded to the patient's allocation. For each patient, the post-operative MRI will be categorized as either "healed" or "non-healed". On post-operative MRI only those patients without tendon defects will be considered to be healed. This will be the primary outcome of the study. The investigators have previously demonstrated this measurement to be reliable.

Secondary Outcome Measures
NameTimeMethod
Simple Shoulder Test (SST) Score Pre-opTo be collected within six months pre-operatively.

The SST score is a patient survey that creates a score on a 12 point scale incorporating questions regarding shoulder function. This survey contains 12 questions and takes \~3 minutes to complete. Higher scores indicate a better outcome.

Simple Shoulder Test (SST) Score 6 monthsTo be collected at 6 months (±4 weeks) post-operatively.

The SST score is a patient survey that creates a score on a 12 point scale incorporating questions regarding shoulder function. This survey contains 12 questions and takes \~3 minutes to complete. Higher scores indicate a better outcome.

Visual Analogue Score (VAS) for pain Pre-opTo be collected within six months pre-operatively.

The VAS pain score is a patient survey that creates a score on a 10 point scale incorporating a single question regarding shoulder pain. This survey takes \<1 minute to complete. Lower scores indicate a better outcome.

American Shoulder and Elbow Surgeons (ASES) Score 6 monthsTo be collected at 6 months (±4 weeks) post-operatively.

The ASES score is a patient survey that creates a score on a 100 point scale incorporating questions regarding shoulder pain and shoulder function. This survey contains 11 questions and takes \~3 minutes to complete. Higher scores indicate a better outcome.

Simple Shoulder Test (SST) Score 6 weeksTo be collected at six weeks (±2 weeks) post-operatively.

The SST score is a patient survey that creates a score on a 12 point scale incorporating questions regarding shoulder function. This survey contains 12 questions and takes \~3 minutes to complete. Higher scores indicate a better outcome.

Visual Analogue Score (VAS) for pain 6 monthsTo be collected at 6 months (±4 weeks) post-operatively.

The VAS pain score is a patient survey that creates a score on a 10 point scale incorporating a single question regarding shoulder pain. This survey takes \<1 minute to complete. Lower scores indicate a better outcome.

Visual Analogue Score (VAS) for pain 6 weeksTo be collected at six weeks (±2 weeks) post-operatively.

The VAS pain score is a patient survey that creates a score on a 10 point scale incorporating a single question regarding shoulder pain. This survey takes \<1 minute to complete. Lower scores indicate a better outcome.

American Shoulder and Elbow Surgeons (ASES) Score Pre-opTo be collected within six months pre-operatively.

The ASES score is a patient survey that creates a score on a 100 point scale incorporating questions regarding shoulder pain and shoulder function. This survey contains 11 questions and takes \~3 minutes to complete. Higher scores indicate a better outcome.

Strength Assessment 12 weeksTo be collected at 12 weeks (±2 weeks) post-operatively.

Rotator cuff strength, as measured with a handheld dynamometer, will be measured. Abduction strength will be measured at 30 degrees of flexion, 30 degrees of abduction, neutral rotation, and full elbow extension. External rotation strength will be measured with the arm in adduction, neutral rotation, and 90 degrees of elbow flexion. These measures will be performed by a single research coordinator.

American Shoulder and Elbow Surgeons (ASES) Score 6 weeksTo be collected at six weeks (±2 weeks) post-operatively.

The ASES score is a patient survey that creates a score on a 100 point scale incorporating questions regarding shoulder pain and shoulder function. This survey contains 11 questions and takes \~3 minutes to complete. Higher scores indicate a better outcome.

American Shoulder and Elbow Surgeons (ASES) Score 12 weeksTo be collected at 12 weeks (±2 weeks) post-operatively.

The ASES score is a patient survey that creates a score on a 100 point scale incorporating questions regarding shoulder pain and shoulder function. This survey contains 11 questions and takes \~3 minutes to complete. Higher scores indicate a better outcome.

Simple Shoulder Test (SST) Score 12 weeksTo be collected at 12 weeks (±2 weeks) post-operatively.

The SST score is a patient survey that creates a score on a 12 point scale incorporating questions regarding shoulder function. This survey contains 12 questions and takes \~3 minutes to complete. Higher scores indicate a better outcome.

Visual Analogue Score (VAS) for pain 12 weeksTo be collected at 12 weeks (±2 weeks) post-operatively.

The VAS pain score is a patient survey that creates a score on a 10 point scale incorporating a single question regarding shoulder pain. This survey takes \<1 minute to complete. Lower scores indicate a better outcome.

Strength Assessment Pre-opTo be collected within six months pre-operatively.

Rotator cuff strength, as measured with a handheld dynamometer, will be measured. Abduction strength will be measured at 30 degrees of flexion, 30 degrees of abduction, neutral rotation, and full elbow extension. External rotation strength will be measured with the arm in adduction, neutral rotation, and 90 degrees of elbow flexion. These measures will be performed by a single research coordinator.

Strength Assessment 6 monthsTo be collected at 6 months (±4 weeks) post-operatively.

Rotator cuff strength, as measured with a handheld dynamometer, will be measured. Abduction strength will be measured at 30 degrees of flexion, 30 degrees of abduction, neutral rotation, and full elbow extension. External rotation strength will be measured with the arm in adduction, neutral rotation, and 90 degrees of elbow flexion. These measures will be performed by a single research coordinator.

Range of motion 6 weeksTo be collected at six weeks (±2 weeks) post-operatively.

Range of motion will be recorded. Research personnel experienced with the use of video will measure active abduction, active forward elevation, active internal rotation in adduction , and active external rotation in adduction. These will be measured sequentially during a single continuous video, first with the video viewing from anteriorly while the subject abducts while standing against a wall, then while viewing from laterally while the subject elevates while standing adjacent to a wall, then while viewing from posteriorly while the subject internally rotates in adduction, and then while viewing from superiorly while the subject externally rotates while sitting in a chair. This protocol has been previously used in many publications. These videos will be saved using subject numbers and then evaluated using a digital protractor by a third-party observer.

Range of motion 12 weeksTo be collected at 12 weeks (±2 weeks) post-operatively.

Range of motion will be recorded. Research personnel experienced with the use of video will measure active abduction, active forward elevation, active internal rotation in adduction , and active external rotation in adduction. These will be measured sequentially during a single continuous video, first with the video viewing from anteriorly while the subject abducts while standing against a wall, then while viewing from laterally while the subject elevates while standing adjacent to a wall, then while viewing from posteriorly while the subject internally rotates in adduction, and then while viewing from superiorly while the subject externally rotates while sitting in a chair. This protocol has been previously used in many publications. These videos will be saved using subject numbers and then evaluated using a digital protractor by a third-party observer.

Magnetic Resonance Imaging (MRI) proximal humeral bone quality Pre-opTo be collected within six months pre-operatively.

Both the pre-operative and post-operative MRI scans will include a ultra-short time-echo (UTE) coronal sequence. On the UTE sequence, maximum humeral cortical thickness will be measured orthogonal to the axis of the shaft five, ten, and fifteen cm distal to the top the head, as we have previously demonstrated this measurement to be accurate and reliable.

Range of motion Pre-opTo be collected within six months pre-operatively.

Range of motion will be recorded. Research personnel experienced with the use of video will measure active abduction, active forward elevation, active internal rotation in adduction , and active external rotation in adduction. These will be measured sequentially during a single continuous video, first with the video viewing from anteriorly while the subject abducts while standing against a wall, then while viewing from laterally while the subject elevates while standing adjacent to a wall, then while viewing from posteriorly while the subject internally rotates in adduction, and then while viewing from superiorly while the subject externally rotates while sitting in a chair. This protocol has been previously used in many publications. These videos will be saved using subject numbers and then evaluated using a digital protractor by a third-party observer.

Magnetic Resonance Imaging (MRI) proximal humeral bone quality Post-opTo be collected at 6 months (±4 weeks) post-operatively.

Both the pre-operative and post-operative MRI scans will include a ultra-short time-echo (UTE) coronal sequence. On the UTE sequence, maximum humeral cortical thickness will be measured orthogonal to the axis of the shaft five, ten, and fifteen cm distal to the top the head, as we have previously demonstrated this measurement to be accurate and reliable.

Strength Assessment 6 weeksTo be collected at six weeks (±2 weeks) post-operatively.

Rotator cuff strength, as measured with a handheld dynamometer, will be measured. Abduction strength will be measured at 30 degrees of flexion, 30 degrees of abduction, neutral rotation, and full elbow extension. External rotation strength will be measured with the arm in adduction, neutral rotation, and 90 degrees of elbow flexion. These measures will be performed by a single research coordinator.

Range of motion 6 monthsTo be collected at 6 months (±4 weeks) post-operatively.

Range of motion will be recorded. Research personnel experienced with the use of video will measure active abduction, active forward elevation, active internal rotation in adduction , and active external rotation in adduction. These will be measured sequentially during a single continuous video, first with the video viewing from anteriorly while the subject abducts while standing against a wall, then while viewing from laterally while the subject elevates while standing adjacent to a wall, then while viewing from posteriorly while the subject internally rotates in adduction, and then while viewing from superiorly while the subject externally rotates while sitting in a chair. This protocol has been previously used in many publications. These videos will be saved using subject numbers and then evaluated using a digital protractor by a third-party observer.

Trial Locations

Locations (1)

University of Utah

🇺🇸

Salt Lake City, Utah, United States

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