Mitochondrial DiseasePhase 1NCT05241262
Study of N-acetylcysteine in the Treatment of Patients With the m.3243A>G Mutation and Low Brain Glutathione Levels
A Phase 1 study testing N-Acetylcysteine in people with Mitochondrial Disease, run by Michio Hirano, MD at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Mitochondrial Disease
- What is being tested?
- N-Acetylcysteine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Jul 2023to Mar 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Columbia University Irving Medical Center
New York, New York, 10032
Kris Engelstad, MS, CGC, 212-342-5767, ke4@cumc.columbia.edu
Michio Hirano, MD
About this study
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
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.
Read the 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
- Being tested
- N-Acetylcysteine
- Keywords
- m.3243A>G, MELAS, diabetes, deafness
- Medical subject headings
- Mitochondrial Diseases, MELAS Syndrome, Diabetes Mellitus, Deafness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-AcetylcysteineDrug
Also called NAC
1800, 3600 or 5400 mg NAC per day (divided into 3 daily doses) depending on dose toxicity plan
| Study group | Role | What they receive |
|---|---|---|
| Active drug (NAC) | Experimental | Participants will receive NAC for 3 months. Receives: Drug: N-Acetylcysteine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 months
Secondary outcomes (5)
Columbia Neurological Score
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.
Measured: 4 months
Change in Global Neuropsychological Score
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.
Measured: 4 months
Change in Functional Exercise Capacity (6 minute walk test (6MWT))
The 6MWT is an objective evaluation of functional exercise capacity assessing the distance a person can walk in six minutes.
Measured: 4 months
Change in Karnofsky Performance Scale (KPS) Score
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).
Measured: 4 months
Change in Brain glutathione (GSH) level
As measured by brain Magnetic resonance Imaging and Magnetic resonance spectroscopy.
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2022
- Study start6 Jul 2023
- Primary completionMar 2026 (estimated)
- Study completionMar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mitochondrial DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 18 Carrier relatives will participate in a dose finding study of NAC.
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Michio Hirano, MD
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Sponsor-investigator, Michio Hirano, MD, Columbia University
- Investigators
- Michio Hirano, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05241262
- Sponsor's protocol ID
- AAAT7415
- Other IDs
- PR 190511
- Status last verified
- Jan 2026
- First submitted
- 3 Feb 2022
- Last updated
- 23 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05241262
- Acronym / sponsor ID
- AAAT7415
- Conditions
- Mitochondrial Disease
- Keywords
- m.3243A>G, MELAS, diabetes, deafness
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Michio Hirano, MDUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- 6 Jul 2023 (actual)
- Primary completion
- Mar 2026 (estimated)
- Study completion
- Mar 2026 (estimated)
- First posted
- 15 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 18 Carrier relatives will participate in a dose finding study of NAC.
| Arm | Type | Receives |
|---|---|---|
| Active drug (NAC) | Experimental | Drug: N-AcetylcysteineParticipants will receive NAC for 3 months. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-AcetylcysteineAlso: NAC1800, 3600 or 5400 mg NAC per day (divided into 3 daily doses) depending on dose toxicity plan | Drug | Active drug (NAC) |
Primary outcome
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.
5 secondary outcomes
Columbia Neurological Score
Time frame: 4 months
Change in Global Neuropsychological Score
Time frame: 4 months
Change in Functional Exercise Capacity (6 minute walk test (6MWT))
Time frame: 4 months
Change in Karnofsky Performance Scale (KPS) Score
Time frame: 4 months
Change in Brain glutathione (GSH) level
Time frame: 4 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Michio Hirano, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing N-Acetylcysteine in people with Mitochondrial Disease, run by Michio Hirano, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kris Engelstad, MS, CGC (212-342-5767, ke4@cumc.columbia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) of NAC (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2026.