A Multiple Ascending Phase 1 Dose Study of N-acetylcysteine in the Treatment of Patients With the m.3243A>G Mutation and Low Brain Glutathione Levels
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD) of NAC
研究概览
简要总结
N-Acetylcysteine (NAC), an anti-oxidant, will be studied to investigate the effects on brain glutathione levels, cognitive skills, motor skills, and quality of life.
A group of 18 participants will take either 1800, 3600 or 5400 mg per day of N-acetylcysteine (NAC) for 3 months in this dose escalation study. The investigators want to determine first if the 3600 mg dose per day is safe and might provide some efficacy. If the 3600 mg dose is safe, then additional participants will be treated with 5400 mg per day of NAC, for up to a total of 18 participants. If the 3600 mg per day dose is unsafe, then participants will be treated with the 1800 mg per day dose. Data from this pilot study will be used to determine the most safe and effective dose of NAC for a future clinical trial.
详细描述
Patients with the m.3243A>G mitochondrial mutation often have low brain glutathione levels. These low levels can reduce the repair processes in the brain to fix toxic chemicals that result from a mitochondrial disorder. The investigators are aware of a potent anti-oxidant, called N-Acetylcysteine (NAC), that may improve the brain glutathione level when taken in sufficient quantity. In turn, cognitive and motor skill impairment may improve as these toxic levels are reduced. will be studied to investigate the effects on brain glutathione levels, cognitive skills, motor skills, and quality of life.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ages 18-80 years
- •Low brain glutathione (GSH) levels as determined by magnetic resonance spectroscopic imaging (MRSI)
- •Individuals who carry, or are suspected of carrying the m.3243A>G mitochondrial mutation (genetic confirmation of mutation required prior to initiation of NAC)
排除标准
- •Individuals with normal brain glutathione levels
- •Pregnant or lactating individuals
- •Medically unstable as determined by the Principal Investigator
- •Allergy to NAC or other sulfur-containing drug
- •Inability to adhere to study protocol
研究组 & 干预措施
Active drug (NAC)
Participants will receive NAC for 3 months.
干预措施: N-Acetylcysteine (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) of NAC
时间窗: 4 months
Establish maximum tolerated dose of NAC by initiating dosing at one level, then increasing or decreasing dose based on toxicity. The MTD is defined as the dose associated with a target probability of dose limiting toxicity (DLT) of 0.10.
次要结局
- Change in Brain glutathione (GSH) level(4 months)
- Columbia Neurological Score(4 months)
- Change in Global Neuropsychological Score(4 months)
- Change in Functional Exercise Capacity (6 minute walk test (6MWT))(4 months)
- Change in Karnofsky Performance Scale (KPS) Score(4 months)
研究者
Michio Hirano, MD
Lucy G. Moses Professor of Neurology
Columbia University