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NCT Number: NCT05241262

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

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.

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Key information

Conditions

Mitochondrial Disease Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Cardiovascular Diseases Central Nervous System Diseases Cerebral Small Vessel Diseases Cerebrovascular Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Deafness Diabetes Mellitus Ear Diseases Endocrine System Diseases Genetic Diseases, Inborn Glucose Metabolism Disorders Hearing Disorders Hearing Loss MELAS Syndrome Metabolic Diseases Metabolism, Inborn Errors Mitochondrial Diseases Mitochondrial Encephalomyopathies Mitochondrial Myopathies Muscular Diseases Musculoskeletal Diseases Nervous System Diseases Neurologic Manifestations Neuromuscular Diseases Nutritional and Metabolic Diseases Otorhinolaryngologic Diseases Pathological Conditions, Signs and Symptoms Sensation Disorders Signs and Symptoms Vascular Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Columbia University Irving Medical Center

New York, 10032, United States

Location status: Recruiting

Location contact

Kris Engelstad, MS, CGC

CONTACT

[email protected]

212-342-5767

Michio Hirano, MD

PRINCIPAL_INVESTIGATOR

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

N-acetylcysteine

Drug

1800, 3600 or 5400 mg NAC per day (divided into 3 daily doses) depending on dose toxicity plan

Other names: NAC

Primary outcomes

  1. Maximum tolerated dose (MTD) of NAC

    Time frame: 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.

Secondary outcomes

  1. Columbia Neurological Score

    Time frame: 4 months

    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.

  2. Change in Global Neuropsychological Score

    Time frame: 4 months

    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.

  3. Change in Functional Exercise Capacity (6 minute walk test (6MWT))

    Time frame: 4 months

    The 6MWT is an objective evaluation of functional exercise capacity assessing the distance a person can walk in six minutes.

  4. Change in Karnofsky Performance Scale (KPS) Score

    Time frame: 4 months

    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).

  5. Change in Brain glutathione (GSH) level

    Time frame: 4 months

    As measured by brain Magnetic resonance Imaging and Magnetic resonance spectroscopy.

Study contacts

Contact information is provided by the study sponsor or research team.

Kris Engelstad, MS, CGC

CONTACT

[email protected]

212-342-5767

Sponsors and collaborators

Lead sponsor

Michio Hirano, MD

Other

Collaborators

  • United States Department of Defense

Registry information

Official study title

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

Important dates

Study start
2023
Primary completion
2026
Study completion
2026
First posted
Feb 15, 2022
Registry last updated
Jan 23, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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