Natural History Study - Mitochondrial Disease

Mitochondrial Encephalomyopathies and Mental Retardation: Investigations of Clinical Syndromes Associated With MtDNA Point Mutations

Status

Recruiting

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT01532791

Enrollment

300

Registered

2012-02-15

Start date

2004-07-01

Completion date

2026-07-01

Last updated

2026-01-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

MELAS or m.3243 A>G Mitochondrial DNA Mutation Carrier

Keywords

MELAS, mitochondrial DNA mutation, mtDNA mutation, mitochondrial DNA, mitochondria, m.3243A>G mutation

Brief 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. 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.

Interventions

None listed

Study design

Observational model

CASE_CONTROL

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

4 Years to No maximum

Healthy volunteers

Yes

Inclusion criteria

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

Exclusion criteria

* Younger than 4 years of age * No confirmed m.3243 A\>G mitochondrial DNA mutation in the family.

Design outcomes

Primary

Measure	Time frame	Description
MRI/MRS	2-3 years	Evaluate structure and function in brain and muscle

Secondary

Measure	Time frame	Description
Biomarkers	2-3 years	Evaluate various biomarkers of disease progression
Motor skills	2-3 years	6 minute walk test to evaluate motor skills
Cognitive function	2-3 years	Evaluate cognitive function through neuropsychological testing
Clinical symptoms	2-3 years	Evaluate clinical symptoms through medical history questionnaires and physical exam
Mutation load	2-3 years	Evaluate heteroplasmy through blood,urine and skin fibroblast evaluations

Countries

United States

Contacts

CONTACTKris Engelstad, MS

ke4@cumc.columbia.edu2123056834

PRINCIPAL_INVESTIGATORMichio Hirano, MD

mh29@cumc.columbia.edu

Outcome results