STARFiSH: Study of Testosterone and rHGH in FSHD: A Proof-of-Concept Study

STARFiSH：睾酮和 rHGH 在 FSHD 中的研究：概念验证研究

• 批准号: 9532311
• 负责人: Chad Rydel Heatwole
• 金额: $ 50.11万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9532311
• 关键词: Adult; Adverse effects; Aerobic; Affect; Age; Atrophic; Biological Markers; Body Composition; Clinical; Clinical Research; Clinical Trials; Combined Modality Therapy; Data; Disease; Drug Kinetics; Dual-Energy X-Ray Absorptiometry; Electrocardiogram; Event; Face; Facioscapulohumeral Muscular Dystrophy; Fatigue; Hereditary Disease; Hip region structure; Human; Impairment; Injections; Insulin-Like Growth Factor I; Laboratories; Measures; Monitor; Muscular Atrophy; Muscular Dystrophies; Participant; Patients; Pharmaceutical Preparations; Physical Function; Population; Prevalence; Process; Protein Biosynthesis; Reporting; Respiratory Muscles; Respiratory physiology; Safety; Serum; Serum Markers; Shoulder; Starfish; Testosterone; Testosterone Enanthate; Therapeutic; Thinness; Time; Walking; arm; associated symptom; burden of illness; clinical development; experience; functional decline; improved; lean body mass; male; men; muscle form; muscle strength; pulmonary function; r-hGH-M; respiratory; safety study; treatment duration

Facioscapulohumeral muscular dystrophy (FSHD) is the second most common adult muscular dystrophy in the world with a global prevalence of ~4:100,000. Clinically, patients with FSHD experience progressive weakness, muscle wasting, fatigue, and respiratory decline. As adult patients with FSHD age, they frequently develop difficulty walking or lose the ability to ambulate due to profound weakness and muscle atrophy. Currently, there are no therapies that have been demonstrated to reverse or even slow the progressive symptoms associated with FSHD. Large scale clinical trials have found that testosterone combined with recombinant human growth hormone (rHGH) (combination therapy) is well tolerated and effective in synergistically improving respiratory function, lean body mass, protein synthesis, strength, and aerobic endurance in healthy adult human populations. Both testosterone and rHGH are readily available and approved for human use but have never been formally studied together in a muscular dystrophy population. We propose a 36-week, proof-of-concept clinical study of the safety and tolerability of daily rHGH combined with biweekly testosterone injections in men with FSHD. All participants will be serially and closely monitored during a 24 week period of combination therapy followed by a 12 week washout period. Safety assessments will include monitoring for medication side effects, laboratory abnormalities, physical exam changes, and EKG alterations. As a secondary objective, we will examine the pharmacokinetic effects of combination therapy on lean body mass and serum biomarkers. Participants will also have serial assessments of their ambulation, strength, physical function, patient-reported disease burden, and respiratory function. Ultimately, this study will generate extensive data regarding the clinical safety, pharmacokinetics, and change in body composition and clinical function associated with combination therapy in a predefined FSHD population.

面肩肱型肌营养不良症 (FSHD) 是第二常见的成人肌营养不良症 全球患病率约为 4:100,000。临床上，FSHD 患者会经历进展性的 虚弱、肌肉萎缩、疲劳和呼吸衰退。随着 FSHD 成年患者年龄的增长，他们经常 由于严重虚弱和肌肉萎缩而出现行走困难或丧失行走能力。 目前，尚无任何疗法被证明可以逆转甚至减缓进展。 与 FSHD 相关的症状。大规模临床试验发现，睾酮与 重组人生长激素 (rHGH)（联合疗法）耐受性良好且有效 协同改善呼吸功能、去脂体重、蛋白质合成、力量和有氧运动 健康成年人群的耐力。睾酮和 rHGH 都很容易获得，并且 批准用于人类，但从未在肌营养不良症人群中进行过正式研究。 我们提议开展一项为期 36 周的概念验证临床研究，研究每日 rHGH 联合用药的安全性和耐受性 患有 FSHD 的男性每两周注射一次睾酮。所有参与者都将受到连续和密切的监控 在 24 周的联合治疗期间，随后是 12 周的清除期。安全评估 将包括监测药物副作用、实验室异常、体检变化和心电图 变更。作为次要目标，我们将检查联合治疗的药代动力学效应 去脂体重和血清生物标志物。参与者还将对其行走能力进行系列评估， 力量、身体功能、患者报告的疾病负担和呼吸功能。最终，这项研究将 生成有关临床安全性、药代动力学和身体成分变化的大量数据， 与预先确定的 FSHD 人群中的联合治疗相关的临床功能。