MELAS or m.3243 A>G Mitochondrial DNA Mutation CarrierNCT01532791
Natural History Study - Mitochondrial Disease
An observational study of MELAS or m.3243 A>G Mitochondrial DNA Mutation Carrier, run by Columbia University at 1 site in United States.
Trial summary
Carriers of the m.3242A>G mutation often have clinical symptoms which can include migraines, seizures, strokes, hearing loss, balance issues, gastrointestinal issues, and many other symptoms. Read more about this study
- Who is it for?
- Ages 4 years and olderHealthy volunteers can take part
- Conditions the study is for
- MELAS or m.3243 A>G Mitochondrial DNA Mutation Carrier
- How many people
- 300 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2004to Jul 2026
- Phase
- Observational
- 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 4 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Carriers of the m.3243A>G mitochondrial DNA point mutation, and their maternal relatives (carrier status documentation not required.). All patients suspected of having an mtDNA point mutation regardless of age, health status, gender, race, or ethnicity will be evaluated. The minimal age of entry into the study will be 4 years or older. We will also evaluate controls (often these are married in relatives).
Who may be able to join
- Known carrier of a the m.3243 A>G mitochondrial mutation, ,or Maternally related to someone who carries the m.3243A>G mitochondrial mutation.
- A family member who is not maternally related to someone who carries the m.3243A>G mitochondrial mutation
Who cannot join
- Younger than 4 years of age
- No confirmed m.3243 A>G mitochondrial DNA mutation in the family.
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
New York, New York, 10032
Kris Engelstad, MS, '-212-305-6834, ke4@cumc.columbia.edu
About this study
Official title: Mitochondrial Encephalomyopathies and Mental Retardation: Investigations of Clinical Syndromes Associated With MtDNA Point Mutations
Carriers of the m.3242A>G mutation often have clinical symptoms which can include migraines, seizures, strokes, hearing loss, balance issues, gastrointestinal issues, and many other symptoms. The investigators would like to learn more about these disorders and have designed a "Natural History Study" to monitor these conditions over time so that physicians and scientists can not only understand the problems that patients have, but work on developing treatments. The focus of the current work is to evaluate known mutation carriers of the m.3243A>G (mitochondrial DNA) and their maternal relatives (carrier status not a requirement for participation). Paternal relatives will serve as controls. This study involves no treatment.
Read the detailed description
The purpose of this study is to investigate the neurological and biochemical consequences of the m.3243 A>G mutation. Mitochondria are the powerhouses of the cell and are controlled by nuclear genetic material (DNA) and mitochondrial (mt) DNA. Mitochondrial DNA mutations impair mitochondrial function, and cause cellular energy failure. These mutations, when present in high abundance, cause neurological signs and symptoms that are clinically obvious. The investigators hypothesize that these mutations, when present in lesser abundance, will cause measurable alterations in the patient's neuropsychological profile and cerebral energy profile. This study does not involve any experimental or approved therapy. The investigators will evaluate the patient's condition with blood/urine tests, neurological exam, MRI/MRS, questionnaires, motor skills functioning, serum and urine biomarkers, and genetic testing.
- Keywords
- MELAS, mitochondrial DNA mutation, mtDNA mutation, mitochondrial DNA, mitochondria, m.3243A>G mutation
- Medical subject headings
- MELAS Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| mtDNA mutation | m.3243 A>G carriers and their maternal relatives Other mutations in the mitochondrial genome may be included | |
| Control | controls (people not maternally related to mutation carriers) Preference is for married in relatives |
What is being measured
The primary outcome is the main question the study is designed to answer.
MRI/MRS
Evaluate structure and function in brain and muscle
Measured: 2-3 years
Secondary outcomes (5)
Biomarkers
Evaluate various biomarkers of disease progression
Measured: 2-3 years
Motor skills
6 minute walk test to evaluate motor skills
Measured: 2-3 years
Cognitive function
Evaluate cognitive function through neuropsychological testing
Measured: 2-3 years
Clinical symptoms
Evaluate clinical symptoms through medical history questionnaires and physical exam
Measured: 2-3 years
Mutation load
Evaluate heteroplasmy through blood,urine and skin fibroblast evaluations
Measured: 2-3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2012 (estimated)
- Study startJul 2004
- Primary completionJul 2026 (estimated)
- Study completionJul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for MELAS or m.3243 A>G Mitochondrial DNA Mutation CarrierStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Michio Hirano, MD, Columbia University
- Investigators
- Michio Hirano, MD, Principal investigator, mh29@cumc.columbia.edu
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01532791
- Sponsor's protocol ID
- AAAB1425
- Other IDs
- 5P01HD032062
- Status last verified
- Jan 2026
- First submitted
- 10 Feb 2012
- Last updated
- 23 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: When applicable, manuscript(s) regarding data will be submitted for publication
Publications
Weiduschat N, Kaufmann P, Mao X, Engelstad KM, Hinton V, DiMauro S, De Vivo D, Shungu D. Cerebral metabolic abnormalities in A3243G mitochondrial DNA mutation carriers. Neurology. 2014 Mar 4;82(9):798-805. doi: 10.1212/WNL.0000000000000169. Epub 2014 Jan 29.
PubMed 24477106Kaufmann P, Engelstad K, Wei Y, Kulikova R, Oskoui M, Sproule DM, Battista V, Koenigsberger DY, Pascual JM, Shanske S, Sano M, Mao X, Hirano M, Shungu DC, Dimauro S, De Vivo DC. Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype. Neurology. 2011 Nov 29;77(22):1965-71. doi: 10.1212/WNL.0b013e31823a0c7f. Epub 2011 Nov 16.
PubMed 22094475Mehrazin M, Shanske S, Kaufmann P, Wei Y, Coku J, Engelstad K, Naini A, De Vivo DC, DiMauro S. Longitudinal changes of mtDNA A3243G mutation load and level of functioning in MELAS. Am J Med Genet A. 2009 Feb 15;149A(4):584-7. doi: 10.1002/ajmg.a.32703.
PubMed 19253345Kaufmann P, Engelstad K, Wei Y, Kulikova R, Oskoui M, Battista V, Koenigsberger DY, Pascual JM, Sano M, Hirano M, DiMauro S, Shungu DC, Mao X, De Vivo DC. Protean phenotypic features of the A3243G mitochondrial DNA mutation. Arch Neurol. 2009 Jan;66(1):85-91. doi: 10.1001/archneurol.2008.526.
PubMed 19139304
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
- Mitochondrial Encephalomyopathies and Mental Retardation: Investigations of Clinical Syndromes Associated With MtDNA Point Mutations
- ClinicalTrials.gov ID
- NCT01532791
- Acronym / sponsor ID
- AAAB1425
- Keywords
- MELAS, mitochondrial DNA mutation, mtDNA mutation, mitochondrial DNA, mitochondria, m.3243A>G mutation
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Jul 2004 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Jul 2026 (estimated)
- First posted
- 15 Feb 2012 (estimated)
- 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.
Carriers of the m.3242A>G mutation often have clinical symptoms which can include migraines, seizures, strokes, hearing loss, balance issues, gastrointestinal issues, and many other symptoms. The investigators would like to learn more about these disorders and have designed a "Natural History Study" to monitor these conditions over time so that physicians and scientists can not only understand the problems that patients have, but work on developing treatments. The focus of the current work is to evaluate known mutation carriers of the m.3243A>G (mitochondrial DNA) and their maternal relatives (carrier status not a requirement for participation). Paternal relatives will serve as controls. This study involves no treatment.
Detailed description
The purpose of this study is to investigate the neurological and biochemical consequences of the m.3243 A>G mutation. Mitochondria are the powerhouses of the cell and are controlled by nuclear genetic material (DNA) and mitochondrial (mt) DNA. Mitochondrial DNA mutations impair mitochondrial function, and cause cellular energy failure. These mutations, when present in high abundance, cause neurological signs and symptoms that are clinically obvious. The investigators hypothesize that these mutations, when present in lesser abundance, will cause measurable alterations in the patient's neuropsychological profile and cerebral energy profile. This study does not involve any experimental or approved therapy. The investigators will evaluate the patient's condition with blood/urine tests, neurological exam, MRI/MRS, questionnaires, motor skills functioning, serum and urine biomarkers, and genetic testing.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| mtDNA mutation | – | –m.3243 A>G carriers and their maternal relatives Other mutations in the mitochondrial genome may be included |
| Control | – | –controls (people not maternally related to mutation carriers) Preference is for married in relatives |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Carriers of the m.3243A>G mitochondrial DNA point mutation, and their maternal relatives (carrier status documentation not required.). All patients suspected of having an mtDNA point mutation regardless of age, health status, gender, race, or ethnicity will be evaluated. The minimal age of entry into the study will be 4 years or older. We will also evaluate controls (often these are married in relatives).
Key inclusion criteria (2 listed)
- Known carrier of a the m.3243 A>G mitochondrial mutation, ,or Maternally related to someone who carries the m.3243A>G mitochondrial mutation.
- A family member who is not maternally related to someone who carries the m.3243A>G mitochondrial mutation
Key exclusion criteria (2 listed)
- Younger than 4 years of age
- No confirmed m.3243 A>G mitochondrial DNA mutation in the family.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
MRI/MRS
Time frame: 2-3 years
Evaluate structure and function in brain and muscle
5 secondary outcomes
Biomarkers
Time frame: 2-3 years
Motor skills
Time frame: 2-3 years
Cognitive function
Time frame: 2-3 years
Clinical symptoms
Time frame: 2-3 years
Mutation load
Time frame: 2-3 years
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.
- Background: PubMed 24477106Weiduschat N, Kaufmann P, Mao X, Engelstad KM, Hinton V, DiMauro S, De Vivo D, Shungu D. Cerebral metabolic abnormalities in A3243G mitochondrial DNA mutation carriers. Neurology. 2014 Mar 4;82(9):798-805. doi: 10.1212/WNL.0000000000000169. Epub 2014 Jan 29.
- Background: PubMed 22094475Kaufmann P, Engelstad K, Wei Y, Kulikova R, Oskoui M, Sproule DM, Battista V, Koenigsberger DY, Pascual JM, Shanske S, Sano M, Mao X, Hirano M, Shungu DC, Dimauro S, De Vivo DC. Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype. Neurology. 2011 Nov 29;77(22):1965-71. doi: 10.1212/WNL.0b013e31823a0c7f. Epub 2011 Nov 16.
- Background: PubMed 19253345Mehrazin M, Shanske S, Kaufmann P, Wei Y, Coku J, Engelstad K, Naini A, De Vivo DC, DiMauro S. Longitudinal changes of mtDNA A3243G mutation load and level of functioning in MELAS. Am J Med Genet A. 2009 Feb 15;149A(4):584-7. doi: 10.1002/ajmg.a.32703.
- Background: PubMed 19139304Kaufmann P, Engelstad K, Wei Y, Kulikova R, Oskoui M, Battista V, Koenigsberger DY, Pascual JM, Sano M, Hirano M, DiMauro S, Shungu DC, Mao X, De Vivo DC. Protean phenotypic features of the A3243G mitochondrial DNA mutation. Arch Neurol. 2009 Jan;66(1):85-91. doi: 10.1001/archneurol.2008.526.
- general website for our available clinical studiesLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. When applicable, manuscript(s) regarding data will be submitted for publication
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
mh29@cumc.columbia.edu
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of MELAS or m.3243 A>G Mitochondrial DNA Mutation Carrier, run by Columbia University 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 2 inclusion and 2 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.
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 (2123056834, ke4@cumc.columbia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MRI/MRS (time frame: 2-3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01532791, which also lists 4 linked publications.
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; AzTrials last refreshed its copy on 30 Oct 2026.