Natural History Study - Mitochondrial Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2015 by Columbia University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Darryl C. De Vivo, Columbia University Identifier:
First received: February 10, 2012
Last updated: December 21, 2015
Last verified: December 2015

February 10, 2012
December 21, 2015
July 2004
January 2020   (final data collection date for primary outcome measure)
MRI/MRS [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
Evaluate structure and function in brain and muscle
Not Provided
Complete list of historical versions of study NCT01532791 on Archive Site
  • Biomarkers [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
    Evaluate various biomarkers of disease progression
  • Motor skills [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
    6 minute walk test to evaluate motor skills
  • Cognitive function [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
    Evaluate cognitive function through neuropsychological testing
  • Clinical symptoms [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
    Evaluate clinical symptoms through medical history questionnaires and physical exam
  • Mutation load [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
    Evaluate heteroplasmy through blood,urine and skin fibroblast evaluations
Not Provided
Not Provided
Not Provided
Natural History Study - Mitochondrial Disease
Mitochondrial Encephalomyopathies and Mental Retardation: Investigations of Clinical Syndromes Associated With MtDNA Point Mutations
Patients with mitochondrial disorders often have clinical symptoms. This 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.
The purpose of this study is to investigate the neurological consequences of mutations in mitochondrial DNA, and the synthesis of energy. 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 and genetic testing.
Observational Model: Case Control
Time Perspective: Prospective
Not Provided
Retention:   None Retained
skin fibroblast blood urine buccal cells hair samples
Non-Probability Sample
Carriers of the m.3243A>G mitochondrial DNA point mutation, and their maternal relatives (carrier status documentation not required) will be enrolled. Paternal relatives will participate as controls. Mitochondrial DNA mutations are genetically determined and transmitted through the maternal lineage. Therefore, this study will focus on family clusters and concentrate on the maternal relatives including the mother and all siblings. 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, or people do do not carry a mitochondrial mutation and are generally family members, not maternally related to a mtDNA mutation carrier
m.3243 A>G Mitochondrial DNA Mutation Carrier or Relative
Not Provided
  • 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

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
January 2022
January 2020   (final data collection date for primary outcome measure)

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.
4 Years and older   (Child, Adult, Senior)
Contact: Kris Engelstad, MS 2123056834
Contact: Darryl De Vivo, MD 2123055244
United States
AAAB1425, 5P01HD032062
Not Provided
Not Provided
Darryl C. De Vivo, Columbia University
Columbia University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Darryl De Vivo, MD
Columbia University
December 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP