NCT05241262

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
18

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Jul 2023

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 3, 2022

Completed
12 days until next milestone

First Posted

Study publicly available on registry

February 15, 2022

Completed
1.4 years until next milestone

Study Start

First participant enrolled

July 6, 2023

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2026

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2026

Completed
Last Updated

January 23, 2026

Status Verified

January 1, 2026

Enrollment Period

2.7 years

First QC Date

February 3, 2022

Last Update Submit

January 22, 2026

Conditions

Mitochondrial Disease

Keywords

m.3243A>GMELASdiabetesdeafness

Outcome Measures

Primary Outcomes (1)

  • 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.

    4 months

Secondary Outcomes (5)

  • Columbia Neurological Score

    4 months

  • Change in Global Neuropsychological Score

    4 months

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

    4 months

  • Change in Karnofsky Performance Scale (KPS) Score

    4 months

  • Change in Brain glutathione (GSH) level

    4 months

Study Arms (1)

Active drug (NAC)

EXPERIMENTAL

Participants will receive NAC for 3 months.

Drug: N-Acetylcysteine

Interventions

N-AcetylcysteineDRUG

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

Also known as: NAC
Active drug (NAC)

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

MeSH Terms

Conditions

Mitochondrial DiseasesMELAS SyndromeDiabetes MellitusDeafness

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Metabolic DiseasesNutritional and Metabolic DiseasesMitochondrial EncephalomyopathiesMitochondrial MyopathiesMuscular DiseasesMusculoskeletal DiseasesBrain Diseases, Metabolic, InbornBrain Diseases, MetabolicBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesCerebral Small Vessel DiseasesCerebrovascular DisordersNeuromuscular DiseasesVascular DiseasesCardiovascular DiseasesMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesGlucose Metabolism DisordersEndocrine System DiseasesHearing LossHearing DisordersEar DiseasesOtorhinolaryngologic DiseasesSensation DisordersNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

CysteineAmino Acids, SulfurSulfur CompoundsOrganic ChemicalsAmino AcidsAmino Acids, Peptides, and Proteins

Study Officials

  • Michio Hirano, MD

    Columbia University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Kris Engelstad, MS, CGC

CONTACT

212-342-5767ke4@cumc.columbia.edu

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: 18 Carrier relatives will participate in a dose finding study of NAC.
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Lucy G. Moses Professor of Neurology

Study Record Dates

First Submitted

February 3, 2022

First Posted

February 15, 2022

Study Start

July 6, 2023

Primary Completion

March 1, 2026

Study Completion

March 1, 2026

Last Updated

January 23, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will not share

Locations

US(1)