Estradiol Supplementation and Rotator Cuff Repair

Официальное название

Estradiol Supplementation and Rotator Cuff Repair: A Preliminary Randomized Trial

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Transdermal estrogen
  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.
• Процедура Rotator Cuff Repair Surgery
  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

Первичные конечные точки

• American Shoulder and Elbow Surgeons (ASES) Score [Срок оценки: 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.]

Вторичные конечные точки (5)

• Simple Shoulder Test (SST) Score [Срок оценки: 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.]
• Visual Analogue Score (VAS) for pain [Срок оценки: 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.]
• Magnetic Resonance Imaging (MRI) [Срок оценки: Within 3 months pre-operatively and at 6 months (±4 weeks) post-operatively.]
• Strength Assessment [Срок оценки: 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.]
• Range of motion [Срок оценки: 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.]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT06318403 · 177012

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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