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.
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)
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
Single group
N-Acetylcysteine
Drug1800, 3600 or 5400 mg NAC per day (divided into 3 daily doses) depending on dose toxicity plan
Maximum tolerated dose (MTD) of NAC
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.
Columbia Neurological Score
The Columbia Neurological Score evaluates patients with cerebral energy failure syndromes and quantifies key neurological examination domains. The Columbia Neurological Score ranges from 0 to 76 with higher scores indicating less clinical severity.
Change in Global Neuropsychological Score
A composite global neuropsychological score is used to assess loss of cognitive function. The global neurological score is derived from measures across a standard neuropsychological battery. Test domains include: Memory, Orientation, Abstract reasoning, Dementia,Language,Word Association, and Naming. The scores range from 0 to 2 with higher scores indicating worsening cognitive function.
Change in Functional Exercise Capacity (6 minute walk test (6MWT))
The 6MWT is an objective evaluation of functional exercise capacity assessing the distance a person can walk in six minutes.
Change in Karnofsky Performance Scale (KPS) Score
KPS assesses functional activities of daily living (ADL). Scores range from 0 to 100 with a score of 0 defined as death and 100 defined as normal; no complaint; no evidence of disease (better outcome).
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Michio Hirano, MD
Lead sponsor
Columbia University
Sponsor institution
United States Department of Defense
Collaborator
