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

性激素补充和肩袖修复：初步随机试验

• 批准号: 10582463
• 负责人: Peter Chalmers
• 金额: $ 16.91万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-01 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10582463
• 关键词: Adverse effects; Aftercare; Age; Agreement; Animals; Appearance; Biology; Clinical; Clinical Trials; Clomiphene; Clomiphene Citrate; Control Groups; Data; Double-Blind Method; Enrollment; Enthesopathies; Estradiol; Estrogen Receptors; Exogenous Hormone Therapy; FDA approved; Failure; Feasibility Studies; Female; Future; Gene Expression; Genetic Polymorphism; Gonadal Steroid Hormones; Gonadotropins; Healthcare Systems; Histologic; Hormonal; Hormones; Human; Hypogonadism; Injury; Intervention; Laboratory Finding; Magnetic Resonance Imaging; Measures; Mus; Musculoskeletal; Operative Surgical Procedures; Outcome; Ovarian Hyperstimulation Syndrome; Pain; Patient Care; Patients; Persons; Pharmaceutical Preparations; Physiological; Pilot Projects; Placebo Control; Placebos; Postoperative Period; Production; Prospective Studies; Questionnaires; Randomized; Research; Research Personnel; Research Proposals; Rotator Cuff; Serum; Shoulder; Shoulder Pain; Side; Source; Standardization; Supplementation; Tendinopathy; Tendon structure; Testing; Testosterone; Time; Tissues; Translating; Visit; Withdrawal; Work; aged; bone; clinical care; compliance behavior; cost; disability; experience; follow-up; gene repair; healing; hormone deficiency; hormone therapy; human male; improved; insight; instrument; interdisciplinary approach; male; men; novel; phase 2 study; pill; pre-clinical; prospective; randomized trial; randomized, clinical trials; randomized, controlled study; receptor; recruit; repaired; response; retention rate; rotator cuff tear; side effect; soft tissue; success

Project Summary/Abstract Rotator cuff tears (RCTs) are among the most common musculoskeletal complaints and are becoming more common. These injuries cost the US health care system $5 billion dollars annually. Prospective randomized and controlled studies have demonstrated that rotator cuff repair (RCR) is indicated for small- and medium-sized tears. Over 500,000 RCRs are performed in the US annually. However, after RCR, healing fails to occur in >25% of patients. Understanding how to improve healing is a critical barrier to success. There is near universal agreement that improving the biology of tendon healing is the key to improving healing. Our prior research suggests Sex Hormone Deficiency (SHD, i.e. hypogonadism) plays a role in RCR healing failure. The research described in the current proposal is the next step towards translating our promising and compelling preclinical and laboratory findings into improved clinical care of patients with RCTs. SHD can be treated with hormone therapy (HT), which is widely utilized, well-tolerated, inexpensive, and FDA approved. Thus, we propose a phase II study to test preliminary efficacy and feasibility. Within aim 1, we will estimate the preliminary efficacy of systemic HT through a randomized, placebo-controlled, double-blinded clinical trial. Hypogonadal men aged 40-80 with SHD will be included. Postoperatively we will evaluate: A. RCR outcomes and B. RCR healing. We hypothesize that outcomes and healing will be better in the HT group than the control group. Within aim 2, we will determine the feasibility of studying systemic HT in the setting of RCR. Although there is extensive clinical experience with HT in human males with SHD, there is almost none in a setting of RCR surgery. To determine the feasibility of a future, larger, multi-center, randomized clinical trial, we will measure the following within the context of the study described in Aim 1: A. recruitment and retention rates, B. patient compliance, C. hormonal response, and D. adverse effects. The expected outcome of the work proposed is demonstration of the preliminary efficacy and feasibility of HT in human males with SHD undergoing RCR. If this intervention is effective and feasible, then a future, larger, well- powered, multi-centered randomized clinical trial with longer follow-up would be warranted. Such a study could improve the treatment of people with RCTs, thereby decreasing a source of significant disability.

项目概要/摘要 肩袖撕裂 (RCT) 是最常见的肌肉骨骼疾病之一， 变得越来越普遍。这些伤害使美国医疗保健系统损失了 50 亿美元 每年。前瞻性随机对照研究表明，肩袖 修复（RCR）适用于中小型撕裂。执行了超过 500,000 次 RCR 每年在美国。然而，RCR 后，>25% 的患者未能愈合。 了解如何改善愈合是成功的关键障碍。有接近普遍的 一致认为改善肌腱愈合的生物学是改善愈合的关键。我们的 先前的研究表明性激素缺乏（SHD，即性腺功能减退症）在 RCR 中发挥着一定作用 愈合失败。当前提案中描述的研究是下一步 将我们有前途且令人信服的临床前和实验室研究结果转化为改进的 随机对照试验患者的临床护理。 SHD 可以通过激素疗法 (HT) 进行治疗，即 广泛使用、耐受性良好、价格低廉且经 FDA 批准。因此，我们提出第二阶段 研究测试初步的有效性和可行性。在目标 1 内，我们将估计初步 通过随机、安慰剂对照、双盲临床试验评估全身性 HT 的疗效。 40-80 岁患有 SHD 的性腺功能减退男性也将包括在内。术后我们将评估：A. RCR 结果和 B. RCR 愈合。我们假设结果和愈合会更好 HT组优于对照组。在目标 2 中，我们将确定学习的可行性 RCR 情况下的全身性 HT。尽管在 HT 方面有丰富的临床经验 患有 SHD 的人类男性，在 RCR 手术中几乎没有。确定 未来更大规模、多中心、随机临床试验的可行性，我们将衡量以下内容 在目标 1 中描述的研究范围内：A. 招募和保留率，B. 患者 依从性，C. 激素反应，D. 不良反应。工作的预期成果 提议证明 HT 在人类男性中的初步功效和可行性 SHD 正在进行 RCR。如果这种干预措施有效且可行，那么未来的、更大的、良好的 需要进行更长期随访的有力、多中心随机临床试验。 这样的研究可以通过随机对照试验改善患者的治疗，从而减少疾病来源 严重残疾。