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.

面肩肩周性肌营养不良症(FSHD)是世界上第二常见的成人肌营养不良症。 全球流行率约为4：100,000。临床上，FSHD患者经历进展性 虚弱、肌肉萎缩、疲劳和呼吸衰退。作为成年FSHD患者，他们经常 由于严重虚弱和肌肉萎缩，导致行走困难或失去行走能力。 目前，还没有被证明可以逆转甚至减缓进展的治疗方法。 与FSHD相关的症状。大规模的临床试验发现，睾酮与 重组人生长激素(RhGH)(联合治疗)耐受性好，疗效显著。 协同改善呼吸功能、瘦体重、蛋白质合成、力量和有氧 健康成人人群中的耐力。睾丸素和重组人生长激素都很容易获得 被批准用于人类，但从未在肌肉营养不良人群中正式研究过。 我们建议进行一项为期36周的联合应用重组人生长激素的安全性和耐受性的临床验证研究。 对患有FSHD的男性进行每两周一次的睾丸素注射。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，然后是12周的冲洗期。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 改装。作为一个次要目标，我们将研究联合治疗的药代动力学效应 瘦体重和血清生物标记物。参与者还将接受一系列关于他们行走的评估， 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广泛数据 在预定义的FSHD人群中与联合治疗相关的临床功能。