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

Rotator Cuff Tears Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04944836
• Other study ID #: RCRHRT
• Status: Recruiting
• Phase: Phase 2
• Start date: March 9, 2023
• Est. completion date: March 1, 2026

Study information

• Verified date: November 2023
• Source: University of Utah
• Contact: Peter Chalmers
• Phone: 8015870063
• Email: chalmerspractice[@]hsc.utah.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 So when the treatment is withdrawn testosterone levels can go very low until feedback mechanisms in the body motivate it to make more.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 information / eligibility

• Status: Recruiting
• Enrollment: 58
• Est. completion date: March 1, 2026
• Est. primary completion date: March 1, 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria

1. A plan for a primary rotator cuff repair

2. Male sex

3. >1 cm tear width, full thickness supraspinatus/infraspinatus tear Exclusion Criteria

1. Active infection

2. Pre-operative testosterone supplementation

3. Known diagnosis of secondary testicular failure or testosterone deficiency

4. Medically unfit for operative intervention

5. Revision surgery

6. Unwillingness to participate in the study, including post-operative imaging

7. Inability to read or comprehend written instructions

8. Prisoner

9. Concomitant patch augmentation or tendon-transfer

10. Untreated prostate cancer

11. Liver disease

12. Pituitary or hypothalamic dysfunction

Related Conditions & MeSH terms

• Rotator Cuff Injuries
• Rotator Cuff Tears

Intervention

Drug:
• Clomiphene Citrate
All 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. In the control group, these will be placebo. These will be taken every other day for seven months beginning four weeks prior to surgery and extending for six months after surgery. After enrollment patients will be randomized. Patient will be assigned to the 2 groups using a permuted block randomization scheme with blocks of size 2, 4, and 6. Prior to initiation of the study opaque sealed envelopes will be prepared and thoroughly shuffled and then used sequentially during the study. These randomization assignments will be available to the pharmacy in a web-based format or by cards in sealed envelopes. A nonparticipant in the study (the pharmacy at our institution) will administer this process.

Procedure:
• Rotator Cuff Repair
The operative protocol will be standardized in all patients. Both the operative protocol and post-operative rehabilitation protocol will be per our standard of care, without alteration. An arthroscopic approach will be used. In all cases a double-row rotator cuff repair using triple-loaded anchor(s) on the medial row will be used. Post-operatively all patients will be placed in a sling for six weeks. Active range of motion exercises will begin at six weeks post-operatively and strengthening will be delayed until 12 weeks post-operatively. In all phases of care our peri-operative and post-operative protocol for study patients will be similar to our current clinical practice to ensure generalizability.

Locations

Country	Name	City	State
United States	University of Utah	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
University of Utah

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serum Hormone Measurement Surgery	Blood will be drawn and the following serum laboratory values will be collected: testosterone, bio-available testosterone, estradiol, all of which are reported in ng/dL.	To be collected at the time of surgery.
Other	Luteinizing Hormone Measurement Surgery	Blood will be drawn and serum luteinizing hormone values will be collected. These are reported in IU/L.	To be collected at the time of surgery.
Other	Serum Hormone Measurement 12 weeks	Blood will be drawn and the following serum laboratory values will be collected: testosterone, bio-available testosterone, and estradiol, all of which are reported in ng/dL.	To be collected at 12 weeks (±2 weeks) post-operatively.
Other	Luteinizing Hormone Measurement 12 weeks	Blood will be drawn and serum luteinizing hormone values will be collected. These are reported in IU/L.	To be collected at 12 weeks (±2 weeks) post-operatively.
Other	Pill Count Surgery	Subjects will be asked how many pills they have taken to determine patient compliance. Deviations from protocol will be recorded.	To be collected at the time of surgery.
Other	Pill Count 6 weeks	Subjects will be asked how many pills they have taken to determine patient compliance. Deviations from protocol will be recorded.	To be collected at six weeks (±2 weeks) post-operatively.
Other	Pill Count 12 weeks	Subjects will be asked how many pills they have taken to determine patient compliance. Deviations from protocol will be recorded.	To be collected at 12 weeks (±2 weeks) post-operatively.
Other	Pill Count 6 months	Subjects will be asked how many pills they have taken to determine patient compliance. Deviations from protocol will be recorded.	To be collected at 6 months (±4 weeks) post-operatively.
Other	Averse Event Assessment Surgery	At each visit patients will be queried regarding adverse events. Patients will asked about the following specific adverse events side effects: anxiety, decreased energy/fatigue, mood instability, difficulty sleeping, decreased libido, visual changes, bleeding, infection, complications from anesthesia, the need for further surgery. In addition, any post-operative injections will be recorded.	To be collected at the time of surgery.
Other	Averse Event Assessment 6 weeks	At each visit patients will be queried regarding adverse events. Patients will asked about the following specific adverse events side effects: anxiety, decreased energy/fatigue, mood instability, difficulty sleeping, decreased libido, visual changes, bleeding, infection, complications from anesthesia, the need for further surgery. In addition, any post-operative injections will be recorded.	To be collected at six weeks (±2 weeks) post-operatively.
Other	Averse Event Assessment 12 weeks	At each visit patients will be queried regarding adverse events. Patients will asked about the following specific adverse events side effects: anxiety, decreased energy/fatigue, mood instability, difficulty sleeping, decreased libido, visual changes, bleeding, infection, complications from anesthesia, the need for further surgery. In addition, any post-operative injections will be recorded.	To be collected at 12 weeks (±2 weeks) post-operatively.
Other	Averse Event Assessment 6 months	At each visit patients will be queried regarding adverse events. Patients will asked about the following specific adverse events side effects: anxiety, decreased energy/fatigue, mood instability, difficulty sleeping, decreased libido, visual changes, bleeding, infection, complications from anesthesia, the need for further surgery. In addition, any post-operative injections will be recorded.	To be collected at 6 months (±4 weeks) post-operatively.
Primary	Magnetic Resonance Imaging (MRI) tendon healing Post-op	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.	To be collected at 6 months (±4 weeks) post-operatively.
Secondary	American Shoulder and Elbow Surgeons (ASES) Score Pre-op	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.	To be collected within six months pre-operatively.
Secondary	American Shoulder and Elbow Surgeons (ASES) Score 6 weeks	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.	To be collected at six weeks (±2 weeks) post-operatively.
Secondary	American Shoulder and Elbow Surgeons (ASES) Score 12 weeks	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.	To be collected at 12 weeks (±2 weeks) post-operatively.
Secondary	American Shoulder and Elbow Surgeons (ASES) Score 6 months	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.	To be collected at 6 months (±4 weeks) post-operatively.
Secondary	Simple Shoulder Test (SST) Score Pre-op	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.	To be collected within six months pre-operatively.
Secondary	Simple Shoulder Test (SST) Score 6 weeks	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.	To be collected at six weeks (±2 weeks) post-operatively.
Secondary	Simple Shoulder Test (SST) Score 12 weeks	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.	To be collected at 12 weeks (±2 weeks) post-operatively.
Secondary	Simple Shoulder Test (SST) Score 6 months	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.	To be collected at 6 months (±4 weeks) post-operatively.
Secondary	Visual Analogue Score (VAS) for pain Pre-op	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.	To be collected within six months pre-operatively.
Secondary	Visual Analogue Score (VAS) for pain 6 weeks	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.	To be collected at six weeks (±2 weeks) post-operatively.
Secondary	Visual Analogue Score (VAS) for pain 12 weeks	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.	To be collected at 12 weeks (±2 weeks) post-operatively.
Secondary	Visual Analogue Score (VAS) for pain 6 months	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.	To be collected at 6 months (±4 weeks) post-operatively.
Secondary	Magnetic Resonance Imaging (MRI) proximal humeral bone quality Pre-op	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.	To be collected within six months pre-operatively.
Secondary	Magnetic Resonance Imaging (MRI) proximal humeral bone quality Post-op	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.	To be collected at 6 months (±4 weeks) post-operatively.
Secondary	Strength Assessment Pre-op	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.	To be collected within six months pre-operatively.
Secondary	Strength Assessment 6 weeks	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.	To be collected at six weeks (±2 weeks) post-operatively.
Secondary	Strength Assessment 12 weeks	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.	To be collected at 12 weeks (±2 weeks) post-operatively.
Secondary	Strength Assessment 6 months	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.	To be collected at 6 months (±4 weeks) post-operatively.
Secondary	Range of motion Pre-op	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.	To be collected within six months pre-operatively.
Secondary	Range of motion 6 weeks	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.	To be collected at six weeks (±2 weeks) post-operatively.
Secondary	Range of motion 12 weeks	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.	To be collected at 12 weeks (±2 weeks) post-operatively.
Secondary	Range of motion 6 months	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.	To be collected at 6 months (±4 weeks) post-operatively.