Estradiol Supplementation and Rotator Cuff Repair (ESTRCR)

Utah System of Higher Education (USHE)

Status and phase

Begins enrollment this month

Phase 2

Conditions

Menopause Related Conditions

Menopause

Rotator Cuff Syndrome

Rotator Cuff Injuries

Rotator Cuff Tears

Treatments

Drug: Transdermal estrogen

Procedure: Rotator Cuff Repair Surgery

Study type

Interventional

Funder types

Other

Identifiers

NCT06318403

177012

Details and patient eligibility

About

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.

Full 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.

Enrollment

58 estimated patients

Sex

Female

Ages

50 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

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

Exclusion Criteria

Active infection
Baseline serum estradiol >20 pg/mL
Infraspinatus or supraspinatus muscle atrophy of greater than or equal to Goutallier grade 3
Pre-operative systemic estradiol supplementation
Medically unfit for operative intervention
Revision surgery
Unwillingness to participate in the study, including post-operative imaging
Inability to read or comprehend written instructions
Prisoner
Concomitant patch augmentation or tendon-transfer
Breast cancer or a history of breast cancer or other estradiol-dependent neoplasia
Liver disease as documented in the medical record
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)
Active arterial thromboembolic disease, such as stroke, myocardiac infarction, a history of these conditions, or a known predisposition to these disorders
Isolated subscapularis tears
Known anaphylactic reaction or hypersensitivity to estradiol, adhesive, or transdermal patches

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

58 participants in 2 patient groups, including a placebo group

Transdermal estradiol patches

Experimental group

Description:

All patients will receive patches with identical labeling from our pharmacy, to be applied twice weekly. In the study group, these will contain 0.025 mg/day of estradiol. In the control group, these will be placebo. These will be applied twice weekly for three months beginning at the time of surgery and extending for three months after surgery.

Treatment:

Procedure: Rotator Cuff Repair Surgery

Drug: Transdermal estrogen

Placebo patches

Placebo Comparator group

Description:

Treatment:

Procedure: Rotator Cuff Repair Surgery