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

Utah System of Higher Education (USHE)

Status and phase: Enrolling; Phase 2

Conditions: Rotator Cuff Tears

Treatments: Procedure: Rotator Cuff Repair; Drug: Clomiphene Citrate

Study type: Interventional

Funder types: Other

Identifiers

NCT04944836

RCRHRT

Details and patient eligibility

About

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.

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 So when the treatment is withdrawn testosterone levels can go very low until feedback mechanisms in the body motivate it to make more.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

Enrollment: 58 estimated patients

Sex: Male

Ages: 40 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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58 participants in 2 patient groups, including a placebo group

Control

Placebo Comparator group

Description:

All 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.

Treatment:

Procedure: Rotator Cuff Repair

Clomiphene

Experimental group

Description:

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. These will be taken every other day for seven months beginning four week prior to surgery and extending for six months after surgery.

Treatment:

Drug: Clomiphene Citrate

Procedure: Rotator Cuff Repair