Clinical trial NCT06318403: Estradiol Supplementation and Rotator Cuff Repair
Official title: Estradiol Supplementation and Rotator Cuff Repair: A Preliminary Randomized Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Rotator Cuff Tears
Rotator Cuff Injuries
Rotator Cuff Syndrome
Menopause Related Conditions
Menopause
Lead sponsor: University of Utah
Sponsor class: OTHER
First posted: 2024-03-19
Enrollment: 58
Sex: FEMALE
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Rotator cuff tears in the shoulder are common causes of pain and disability, often fail to heal with surgery, and tears, worse outcomes after surgery, and failure of healing are associated with estradiol deficiency. In this study, post-menopausal women will be randomized to either estradiol patches or placebo patches after repair of the rotator cuff. The purpose of this study is to determine whether estradiol patches show promise in improving shoulder pain, strength, muscle volumes, and function when given with rotator cuff repair.

Detailed description: Injuries to the rotator cuff are among the most common musculoskeletal complaints and are increasing in incidence. Multiple studies have demonstrated that rotator cuff repair (RCR) improves outcomes for rotator cuff tears. Over 500,000 RCRs are performed in the US annually. When both surgical and non-operative treatment are included, rotator cuff injuries cost the United States over $5 billion dollars annually. After RCR, tendon healing fails to occur in \>20% of patients. Improving tendon healing is thus a critical barrier to success. The field has arrived at a consensus that improving tendon biology is the key to improving tendon healing. Our prior human and animal research demonstrates that estradiol deficiency contributes to rotator cuff injuries and poor outcomes after RCR and estradiol supplementation improves RCR healing and outcomes. With this study we propose to translate these promising and compelling findings into improved clinical care of patients with rotator cuff injuries. Estradiol deficiency can be treated with hormone therapy (HT), which is widely utilized, well-tolerated, inexpensive, and FDA approved. In this study, we will conduct a phase II study of the efficacy and feasibility of HT within the setting of RCR. We hypothesize that compliance and response rates will be high while adverse events will be infrequent and equally common with estradiol patches and placebo patches. We also hypothesize that outcomes and healing will be better in the HT group than the control group. To test these hypotheses, we will conduct a randomized, placebo-controlled, double-blinded clinical trial to measure recruitment and retention rates, compliance with treatment, response to treatment of serum hormone levels, estimated effect size for power calculations, and adverse events. Postoperatively, we will evaluate validated patient-reported outcomes and tendon healing and rotator cuff muscle volumes utilizing magnetic resonance imaging. If efficacy and tolerability are demonstrated, a future large, multi-center, randomized clinical trial will be warranted. We expect these data will support the use of estradiol as a promising approach to improved healing and outcomes, supporting a future, larger, well-powered, multi-centered randomized clinical trial with longer follow-up. Such a study could improve the treatment of people with rotator cuff injuries, thereby decreasing a source of significant disability. If our hypotheses are confirmed, it would shift the paradigm on the treatment of problems with tendons and their attachments to bone throughout the body.

Eligibility criteria: Inclusion Criteria

1. A plan for a primary rotator cuff repair
2. Female sex (assigned sex at birth)
3. \>1 cm tear width, full thickness supraspinatus/infraspinatus tear
4. Post-menopausal, as defined by at least twelve months since last menses
5. Age 50-80

Exclusion Criteria

1. Active infection
2. Baseline serum estradiol \>20 pg/mL
3. Infraspinatus or supraspinatus muscle atrophy of greater than or equal to Goutallier grade 3
4. Pre-operative systemic estradiol supplementation
5. Medically unfit for operative intervention
6. Revision surgery
7. Unwillingness to participate in the study, including post-operative imaging
8. Inability to read or comprehend written instructions
9. Prisoner
10. Concomitant patch augmentation or tendon-transfer
11. Breast cancer or a history of breast cancer or other estradiol-dependent neoplasia
12. Liver disease as documented in the medical record
13. Active venous thromboembolic disease, such as deep venous thrombosis, pulmonary embolism, a history of these conditions, or a known predisposition to these disorders (such as Protein C, protein S, or antithrombin deficiency)
14. Active arterial thromboembolic disease, such as stroke, myocardiac infarction, a history of these conditions, or a known predisposition to these disorders
15. Isolated subscapularis tears
16. Known anaphylactic reaction or hypersensitivity to estradiol, adhesive, or transdermal patches

Primary outcomes:
measure: American Shoulder and Elbow Surgeons (ASES) Score
timeFrame: To be collected within 3 months pre-operatively and at 6 weeks (±2 weeks), 12 weeks (±2 weeks), and 6 months (±4 weeks) post-operatively.
Secondary outcomes:
measure: Simple Shoulder Test (SST) Score
timeFrame: To be collected within 3 months pre-operatively and at 6 weeks (±2 weeks), 12 weeks (±2 weeks), and 6 months (±4 weeks) post-operatively.
measure: Visual Analogue Score (VAS) for pain
timeFrame: To be collected within 3 months pre-operatively and at 6 weeks (±2 weeks), 12 weeks (±2 weeks), and 6 months (±4 weeks) post-operatively.
measure: Magnetic Resonance Imaging (MRI)
timeFrame: Within 3 months pre-operatively and at 6 months (±4 weeks) post-operatively.
measure: Strength Assessment
timeFrame: To be collected within 3 months pre-operatively and at 6 weeks (±2 weeks), 12 weeks (±2 weeks), and 6 months (±4 weeks) post-operatively.
measure: Range of motion
timeFrame: To be collected within 3 months pre-operatively and at 6 weeks (±2 weeks), 12 weeks (±2 weeks), and 6 months (±4 weeks) post-operatively.
Other outcomes:
measure: Serum Hormone Measurement
timeFrame: To be collected within 3 months pre-operatively, at 6 weeks (±1 week) after starting medication, and at 12 weeks (±2 weeks) after starting medication.
measure: Patch Count
timeFrame: 6 weeks (±2 weeks) post-operatively, 12 weeks (±2 week) post-operatively.
measure: Averse Event Assessment
timeFrame: To be collected at every patient visit, including 6 weeks (±2 weeks) after surgery, 12 weeks (±2 weeks) after surgery, and 6 months (±4 weeks) after surgery.
Locations:
Study officials:
References: