对杜氏肌营养不良症青春期延迟的睾酮治疗的临床结局的观察性研究。
Observational study of clinical outcomes for testosterone treatment of pubertal delay in Duchenne muscular dystrophy.
机构信息
John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University, Newcastle, UK.
Institute of Genetic Medicine, Newcastle University and Great North Children's Hospital, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne, UK.
出版信息
BMC Pediatr. 2019 Apr 25;19(1):131. doi: 10.1186/s12887-019-1503-x.
BACKGROUND
Adolescents with DMD treated with chronic high dose GC therapy typically have profound pubertal delay. Testosterone, the main circulating androgen in men, promotes virilisation and growth with associated accrual of fat-free muscle mass and bone mineral content. Testosterone therapy is routinely used to mimic the normal stages of pubertal development in patients with hypogonadotrophic hypogonadism, androgen deficiency secondary to testicular disease and in constitutional delay of growth and puberty (CDGP). Improved life expectancy in DMD has meant that more adolescents are eligible for testosterone supplementation but there is little objective data regarding the impact of this treatment on muscle structure and function, bone integrity and overall well-being.
METHODS
This is a single centre observational clinical trial (NCT02571205) that aims to follow the progress of 15 adolescents with Duchenne muscular dystrophy and delayed puberty as they are managed with incremental testosterone therapy to induce puberty. Subjects will all be treated with a steadily increasing dose of testosterone administered by injection every 4 weeks and data will be collected to help us determine the effectiveness and tolerability of the described treatment regimen. We will use the data to explore the effects of testosterone on pubertal development, growth, muscle strength and function, bone mineral density, body composition with a detailed record of any adverse events. We will also carry out interviews to explore the boys' views on the tolerability of the regimen. The study will last for 27 months in total for each participant.
DISCUSSION
Our experience has indicated that testosterone treatment in adolescents with DMD is liked and well tolerated but we have not collected objective data on a specific treatment regimen and there is no current consensus. Testosterone supplementation is not part of the standard of care of pubertal delay in DMD but inclusion in future protocols may be appropriate depending on the results of this trial.
TRIAL REGISTRATION
EudraCT Number: 2015-003195-68. Research Registry & References: Clinical trials.gov- NCT02571205 (registered 8/10/15).
背景
接受慢性高剂量 GC 治疗的 DMD 青少年通常存在明显的青春期延迟。睾酮是男性主要的循环雄激素，可促进男性性征的出现和生长，同时增加无脂肪肌肉质量和骨矿物质含量。睾酮治疗通常用于模仿促性腺激素低下性性腺功能减退症、睾丸疾病引起的雄激素缺乏以及生长和青春期发育迟缓（CDGP）患者的正常青春期发育阶段。DMD 的预期寿命延长意味着更多的青少年有资格接受睾酮补充治疗，但关于这种治疗对肌肉结构和功能、骨骼完整性和整体健康的影响，几乎没有客观数据。
方法
这是一项单中心观察性临床试验（NCT02571205），旨在跟踪 15 名患有杜氏肌营养不良症和青春期延迟的青少年，因为他们正在接受递增剂量的睾酮治疗以诱导青春期。所有受试者都将接受每 4 周注射一次的逐渐增加剂量的睾酮治疗，收集数据以帮助我们确定描述的治疗方案的有效性和耐受性。我们将利用这些数据来探讨睾酮对青春期发育、生长、肌肉力量和功能、骨密度、身体成分的影响，并详细记录任何不良反应。我们还将进行访谈，以探讨男孩对该方案耐受性的看法。每位参与者的研究总时长为 27 个月。
讨论
我们的经验表明，DMD 青少年的睾酮治疗是可以接受的，但我们没有收集特定治疗方案的客观数据，目前也没有共识。睾酮补充治疗不是 DMD 青春期延迟标准治疗的一部分，但根据本试验的结果，将来的方案中可能需要包含。
试验注册
EudraCT 编号：2015-003195-68。研究注册和参考：Clinical trials.gov-NCT02571205（注册于 2015 年 8 月 10 日）。
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