Tadalafil as an Adjuvant to Therapy for Duchenne Muscular Dystrophy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Change in post-contractile BOLD response after tadalafil dosing
研究概览
简要总结
This project will assess the vascular responsiveness in leg muscles of boys with Duchenne muscular dystrophy (DMD) to one single dose of tadalafil, a common vasodilator drug, using non-invasive techniques (MRI or Doppler ultrasound) and exercise testing. These findings will provide proof of concept for a subsequent intervention study to demonstrate efficacy of longer-term tadalafil to counter sympathetic vasoconstriction and slow disease progression in DMD. It will also inform whether a group of patients do not respond to the drug.
详细描述
This project will target up to 25 ambulatory boys with DMD aged 7-13 years. Because the vascular impact of tadalafil is immediate, we will confirm that the drug target is valid target in lower extremities by assessing the change in post-exercise microvascular perfusion using Blood Oxygen Level-Dependent (BOLD) MRI or change in post-exercise hyperemia using Doppler ultrasonography. We will also assess the functional impact of the drug through exercise testing. Patients will be randomized to undergo the above-mentioned assessments with or without the study drug on two separate visits. Time function tests, MRI-based fat fraction and inflammation measurements will also be obtained in all patients, thus characterizing disease severity and provide a sampling of information on whether a subset of patients do not respond to the drug. This information may be used to inform future trials as to the appropriate target population for PDE5i as well as account for potential failures in a previously published phase 3 clinical trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 7 Years 至 13 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of DMD confirmed by 1) clinical history with features before the age of five, 2) physical examination, 3) elevated serum creatine kinase level and 4) absence of dystrophin expression, as determined by immunostaining or Western blot (<2%) and/or DNA confirmation of dystrophin mutation.
- •Minimum entry age of 7.0 years
- •Ambulatory
排除标准
- •Older than 13.0 years of age
- •Contraindication to an MR examination (e.g. aneurysm clip, severe claustrophobia, magnetic implants)
- •Presence of unstable medical problems
- •Presence of a secondary condition that impacts muscle function or muscle metabolism (e.g. myasthenia gravis, endocrine disorder, mitochondrial disease)
- •Contraindications to Tadalafil (use of nitrates, alpha-adrenergic blockers, other PDE5A inhibitors)
研究组 & 干预措施
Tadalafil plus BOLD-MRI (Schedule A)
The intervention is the same as in Schedule B; this arm will use BOLD-MRI as the technique to monitor drug impact on skeletal muscle.
干预措施: Tadalafil (Drug)
Tadalafil plus Doppler ultrasound (Schedule B)
The intervention is the same as in Schedule A; this arm will use Doppler ultrasound as the technique to monitor drug impact on skeletal muscle.
干预措施: Tadalafil (Drug)
结局指标
主要结局
Change in post-contractile BOLD response after tadalafil dosing
时间窗: MRI will be done 3 hours after dosing/no-dosing on two separate study visits
MRI technique to measure microvascular function in skeletal muscle
Change in post-exercise hyperemia after tadalafil dosing
时间窗: Doppler ultrasound will be done 3 hours after dosing/no-dosing on two separate study visits
Doppler ultrasound will be used to measure blood flow
次要结局
- Change in submaximal exercise capacity after tadalafil dosing(Cycle testing will be done 4 hours after dosing/no-dosing on two separate study visits)