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
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.

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

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Mitochondrial Encephalomyopathies and Mental Retardation: Investigations of Clinical Syndromes Associated With MtDNA Point Mutations

Resource links provided by NLM:

Further study details as provided by Columbia University:

Primary Outcome Measures:
  • MRI/MRS [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
    Evaluate structure and function in brain and muscle

Secondary Outcome Measures:
  • 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

Biospecimen Retention:   None Retained
skin fibroblast blood urine buccal cells hair samples

Estimated Enrollment: 300
Study Start Date: July 2004
Estimated Study Completion Date: January 2022
Estimated Primary Completion Date: January 2020 (Final data collection date for primary outcome measure)
mtDNA mutation
m.3243 A>G carriers and their maternal relatives Other mutations in the mitochondrial genome may be included
controls (people not maternally related to mutation carriers) Preference is for married in relatives

Detailed Description:
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.

Ages Eligible for Study:   4 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
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

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01532791

Contact: Kris Engelstad, MS 2123056834
Contact: Darryl De Vivo, MD 2123055244

United States, New York
Columbia University Recruiting
New York City, New York, United States, 10032
Contact: Kris Engelstad, MS    212-305-6834   
Sponsors and Collaborators
Columbia University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Darryl De Vivo, MD
  More Information

Additional Information:
Responsible Party: Darryl C. De Vivo, Sidney Carter Professor of Neurology and Professor of Pediatrics, Columbia University Identifier: NCT01532791     History of Changes
Other Study ID Numbers: AAAB1425  5P01HD032062 
Study First Received: February 10, 2012
Last Updated: December 21, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Columbia University:
mitochondrial DNA mutation
mtDNA mutation
mitochondrial DNA
m.3243A>G mutation

Additional relevant MeSH terms:
Mitochondrial Encephalomyopathies
Brain Diseases
Brain Diseases, Metabolic
Central Nervous System Diseases
Metabolic Diseases
Mitochondrial Diseases
Mitochondrial Myopathies
Muscular Diseases
Musculoskeletal Diseases
Nervous System Diseases
Neuromuscular Diseases processed this record on May 26, 2016