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

NCT ID: NCT05241262

Last Updated: 2026-01-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-06
• Study Completion Date: 2026-03-31

Brief Summary

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.

Detailed 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.

Conditions

Mitochondrial Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Active drug (NAC)

Participants will receive NAC for 3 months.

Group Type: EXPERIMENTAL

N-Acetylcysteine

Intervention Type: DRUG

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

Interventions

N-Acetylcysteine

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

Intervention Type: DRUG

Other Intervention Names

NAC

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

United States Department of Defense

FED

Sponsor Role: collaborator

Michio Hirano, MD

OTHER

Sponsor Role: lead

Responsible Party

Michio Hirano, MD

Lucy G. Moses Professor of Neurology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Michio Hirano, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University Irving Medical Center

New York, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Kris Engelstad, MS, CGC

Role: CONTACT

ke4@cumc.columbia.edu

212-342-5767

Facility Contacts

Kris Engelstad, MS, CGC

Role: primary

ke4@cumc.columbia.edu

212-342-5767

Other Identifiers

PR 190511

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

AAAT7415

Identifier Type: -

Identifier Source: org_study_id