Mechanistic Assessment of N-Acetylcysteine as an Antioxidant Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Through Dose Response and Treatment Target Engagement
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 95
- 试验地点
- 1
- 主要终点
- Change in GSH levels of treatment response: measure 2
研究概览
简要总结
Chronic fatigue syndrome/myalgic encephalomyelitis (ME/CFS) is an unexplained multisymptom/multisystem disorder for which there are currently no validated treatments. The present exploratory clinical trial aims to advance our understand of the mechanisms of in situ GSH synthesis control through assessment of the response of brain GSH and plasma markers of oxidative stress to different doses of NAC in comparison to placebo, as a potential treatment for ME/CFS that would provide neuroprotection against oxidative stress by restoring cortical GSH reserves. If successful, this exploratory clinical trial would address a significant public health concern by shedding new light onto the mechanisms of action of NAC in brain GSH restoration, which could open a new avenue for the development of potentially effective treatments for a disorder, ME/CFS, that currently has none.
详细描述
This phase two, single-site study will utilize a double-blind, placebo-controlled, randomized, pre-/post-treatment design to investigate the effect of NAC dosing on brain GSH levels and measure temporally concordant plasma levels of several established circulating markers of oxidative stress. Three study groups, of 20 subjects each (for a total of 60 who completed all components of the study), will each be administered a different dose (0 mg/day, 900mg/day, 3600mg/day) of the study intervention over a four week period; N-acetylcysteine (NAC) treatment. Subjects receiving 0 mg/day dose will be administered a placebo. Baseline visit assessments will include blood collection, survey questionnaires, MRI and MRS imaging. Subjects whose initial screening confirms low GSH level at baseline will be provided with a 4-week supplement of anonymized NAC or placebo caplets. After 4 weeks, subjects will then undergo a follow-up visit to repeat the baseline assessments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 21 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females, ages 21 to 60 years (inclusive).
- •Baseline GSH levels at or less than a predefined cutoff value.
- •Primary diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
- •Willing and capable of providing informed consent.
排除标准
- •Significant and/or comorbid axis I (especially mood and anxiety) and axis II disorders.
- •Any significant neurological illness or impairment.
- •Other unstable medical conditions (asthma, hypertension, endocrine or metabolic disease, etc).
- •History alcohol abuse.
- •Positive urine toxicology at screening and on days of assessments.
- •Positive pregnancy test at screening or on days of assessments.
- •Contra-indication for clinical MRI scan (e.g., pacemaker, metallic prosthesis).
- •Baseline GSH levels higher than a predefined cutoff value.
研究组 & 干预措施
NAC 900mg/day
Subjects who pass screening may be randomly assigned to this arm where they will self administer NAC 900mg/day caplets for a four week period
干预措施: NAC 900mg/day (Drug)
NAC 3600mg/day
Subjects who pass screening may be randomly assigned to this arm where they will self administer NAC 3600mg/day caplets for a four week period
干预措施: NAC 3600mg/day (Drug)
NAC 0mg/day (Placebo)
Subjects who pass screening may be randomly assigned to this arm where they will self administer NAC 0mg/day (placebo) caplets for a four week period
干预措施: NAC 0mg/day (Placebo) (Drug)
结局指标
主要结局
Change in GSH levels of treatment response: measure 2
时间窗: pre/post 4 weeks of NAC supplementation
Levels of striatal GSH, as measured in vivo with 1H MRS
Change in GSH levels of treatment response: measure 1
时间窗: pre/post 4 weeks of NAC supplementation
Levels of occipital cortex GSH, as measured in vivo with 1H MRS
次要结局
- Change of levels of ventricular CSF lactate of treatment response(pre/post 4 weeks of NAC supplementation)
- Change in Oxidative stress levels of treatment response: measure 3(pre/post 4 weeks of NAC supplementation)
- Change of regional cerebral blood flow (rCBF) of treatment response(pre/post 4 weeks of NAC supplementation)
- Change in Oxidative stress levels of treatment response: measure 2(pre/post 4 weeks of NAC supplementation)
- Change in Oxidative stress levels of treatment response: measure 1(pre/post 4 weeks of NAC supplementation)
- Change in Oxidative stress levels of treatment response: measure 6(pre/post 4 weeks of NAC supplementation)
- Change in Oxidative stress levels of treatment response: measure 4(pre/post 4 weeks of NAC supplementation)
- Change in Oxidative stress levels of treatment response: measure 5(pre/post 4 weeks of NAC supplementation)