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Study of N-acetylcysteine in the Treatment of Patients With the m.3243A>G Mutation and Low Brain Glutathione Levels

Study of N-acetylcysteine in the Treatment of Patients With the m.3243A>G Mutation and Low Brain Glutathione Levels

Recruiting
18-80 years
All
Phase 1

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Overview

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.

Description

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.

Eligibility

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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

Study details
    Mitochondrial Disease

NCT05241262

Michio Hirano, MD

26 January 2024

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