Columbia SMA Project: 4-AP as a Potential SMA Therapeutic Agent and Biological Mechanisms of Action
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Six Minute Walk Test (6MWT) With Kinematic Evaluation of Gait (Short Term)
研究概览
简要总结
The purpose of this study is to assess whether 4-AP (Dalfampridine-ER, Ampyra) improves walking ability and endurance in adult patients with Spinal muscular atrophy (SMA) Type 3 compared to placebo and whether the duration of treatment affects outcome.
详细描述
Spinal muscular atrophy (SMA) is a genetically determined neuromuscular disorder that results in muscle weakness and impaired functional mobility. Fatigue is a common symptom in SMA with a resultant impact on physical function and quality of life however the precise mechanisms are unknown. At present there is no treatment for SMA. There is evidence that 4-AP improves function in SMA animal models. In patients with multiple sclerosis, 4-AP was found to improve walking ability and diminish fatigue. The purpose of the study is to determine whether treatment with 4-AP is associated with an increase in walking speed and endurance compared to placebo and whether the duration of treatment affects outcome. The study comprises a short term treatment trial in which participants are treated for 2 weeks with 4-AP and placebo in random sequence followed by a long treatment trial of 6 weeks in which patients are also treated with placebo and 4 AP. The primary outcome measure of the clinical study will be the six minute walk test (6MWT), which has been documented to be a valid and sensitive instrument to identify fatigue among ambulatory SMA patients. We will also assess the effect of 4-AP on muscle and nerve electrical function via electromyography (EMG) during the short term trial. Results of this study may provide support for larger clinical trials.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 to 50 years at the time of enrollment
- •Have genetically confirmed SMA 3 (homozygous absence of SMN1 exon 7)
- •Ability to walk at least 25 meters without assistance
- •Be free of major orthopedic deformities (i.e. scoliosis, contractures)
- •Normal Cystatin C clearance (> 80 ml/min)
排除标准
- •Patients with a history of seizures
- •Patients with any renal impairment
- •Inability to comply with the study procedures
- •Unstable medical illness
- •Any ventilatory assistance
- •Taking experimental medication for SMA other than under this protocol
- •Pregnancy or lactation
- •Menstruating women, not sterilized or not using effective birth control
- •Planning to undergo scoliosis surgery within the next 10 months
- •Inability to give informed consent
研究组 & 干预措施
4-aminopyridine (Ampyra)
10 mg tab/ 1 tab twice daily
干预措施: 4-aminopyridine (Drug)
Sugar pill
Placebo 1 tab /twice daily
干预措施: Placebo (Drug)
结局指标
主要结局
Six Minute Walk Test (6MWT) With Kinematic Evaluation of Gait (Short Term)
时间窗: Day 14 of each short-term intervention period
The primary outcome measure will be distance walked in the 6MWT. This measure is an objective evaluation of functional capacity which measures the distance a person can walk quickly in six minutes and is most representative of a person's ability because the test intensity is self-selected. The 6MWT can be safely performed in ambulatory SMA patients and correlates with standard SMA outcome measures including timed walking tests. In SMA, the 6MWT may be more sensitive to clinically meaningful changes in patients with type 3 SMA as it is a direct measure of their functional mobility.
Six Minute Walk Test (6MWT) With Kinematic Evaluation of Gait (Long Term)
时间窗: Day 42 of each long-term intervention period
The primary outcome measure will be distance walked in the 6MWT. This measure is an objective evaluation of functional capacity which measures the distance a person can walk quickly in six minutes and is most representative of a person's ability because the test intensity is self-selected. The 6MWT can be safely performed in ambulatory SMA patients and correlates with standard SMA outcome measures including timed walking tests. In SMA, the 6MWT may be more sensitive to clinically meaningful changes in patients with type 3 SMA as it is a direct measure of their functional mobility.
次要结局
- Hammersmith Functional Motor Scale, Expanded (HFMSE) (Short Term)(Day 14 of each short-term intervention period)
- Hammersmith Functional Motor Scale, Expanded (HFMSE) (Long Term)(Day 42 of each long-term intervention period)
- Manual Muscle Testing (MMT) Total Score (Short Term)(Day 14 of each short-term intervention period)
- Manual Muscle Testing (MMT) Total Score (Long Term)(Day 42 of each long-term intervention period)
- Motor Unit Number Estimation (MUNE)(Day 14 of each short-term intervention period)
研究者
Claudia Chiriboga
Professor of Neurology and Pediatrics at CUMC
Columbia University