Natural History Study - Mitochondrial Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by Columbia University
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Darryl C. De Vivo, Columbia University
ClinicalTrials.gov Identifier:
NCT01532791
First received: February 10, 2012
Last updated: August 10, 2016
Last verified: August 2016
  Purpose
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.

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

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)
Groups/Cohorts
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

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.
  Eligibility

Ages Eligible for Study:   4 Years and older   (Child, Adult, Senior)
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.). 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).
Criteria

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 ClinicalTrials.gov identifier: NCT01532791

Contacts
Contact: Kris Engelstad, MS 2123056834 ke4@cumc.columbia.edu
Contact: Darryl De Vivo, MD 2123055244 dcd1@cumc.columbia.edu

Locations
United States, New York
Columbia University Recruiting
New York City, New York, United States, 10032
Contact: Kris Engelstad, MS    212-305-6834    ke4@cumc.columbia.edu   
Sponsors and Collaborators
Columbia University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Principal Investigator: Darryl De Vivo, MD dcd1@columbia.edu
  More Information

Additional Information:
Publications:
Responsible Party: Darryl C. De Vivo, Sidney Carter Professor of Neurology and Professor of Pediatrics, Columbia University
ClinicalTrials.gov Identifier: NCT01532791     History of Changes
Other Study ID Numbers: AAAB1425  5P01HD032062 
Study First Received: February 10, 2012
Last Updated: August 10, 2016
Health Authority: United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: When applicable, manuscript(s) regarding data will be submitted for publication

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

Additional relevant MeSH terms:
Mitochondrial Diseases
Mitochondrial Encephalomyopathies
Metabolic Diseases
Mitochondrial Myopathies
Muscular Diseases
Musculoskeletal Diseases
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neuromuscular Diseases

ClinicalTrials.gov processed this record on August 23, 2016