Clinical trial NCT05241262: Study of N-acetylcysteine in the Treatment of Patients With the m.3243A>G Mutation and Low Brain Glutathione Levels
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Mitochondrial Disease
Keywords: m.3243A>G
MELAS
diabetes
deafness
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2022-02-15
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 18 Carrier relatives will participate in a dose finding study of NAC.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Maximum tolerated dose (MTD) of NAC
timeFrame: 4 months
Secondary outcomes:
measure: Columbia Neurological Score
timeFrame: 4 months
measure: Change in Global Neuropsychological Score
timeFrame: 4 months
measure: Change in Functional Exercise Capacity (6 minute walk test (6MWT))
timeFrame: 4 months
measure: Change in Karnofsky Performance Scale (KPS) Score
timeFrame: 4 months
measure: Change in Brain glutathione (GSH) level
timeFrame: 4 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Michio Hirano, MD
role: PRINCIPAL_INVESTIGATOR
References: