Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Natural History and Advanced Genetic Study of Pyruvate Dehydrogenase Complex Deficiencies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03056794
Recruitment Status : Recruiting
First Posted : February 17, 2017
Last Update Posted : May 5, 2020
Sponsor:
Collaborators:
Rare Diseases Clinical Research Network
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Jirair K. Bedoyan, MD, PhD, University Hospitals Cleveland Medical Center

Brief Summary:
Children and adults with pyruvate dehydrogenase complex deficiency (PDCD) are participating in a research study seeking to better understand the genetic causes, symptoms, usefulness of current treatments, and outcomes for these disorders. The research project involves completing a questionnaire about the individual or family's medical history and experiences with PDCD, review of medical records by the researchers, and in some cases, advanced genetic testing.

Condition or disease Intervention/treatment
Pyruvate Dehydrogenase Complex Deficiency Disease Other: No intervention

Detailed Description:

Pyruvate dehydrogenase complex deficiencies (PDCDs) are a major class of mitochondrial diseases, limiting oxidation of carbohydrate for energy production, which is especially important in the brain. So far, there is not a definitive treatment for these disorders. This study, "Advanced Genetic Study and Pilot Newborn Screening for Disorders of Pyruvate Metabolism," will continue with the created database with information that is collected over a long period of time about patients with PDCDs. This database is part of the existing North American Mitochondrial Disease Consortium (NAMDC) Patient Data Registry and Biorepository database. The study will collect data specific to PDC deficiencies, including data that is derived from patients/families. Approximately 75 subjects with confirmed PDCD will be enrolled over 5 years. The genetic basis and pathophysiology will be explored in up to a third of confirmed PDC deficient patients, who currently have not been found to have an identified mutation in DLD or any of the five "primary" PDC-specific genes (PDHA1, PDHB, DLAT, PDHX, and PDP1), and who might benefit from different treatments.

The specific aims of the study are:

  1. Continue to add to the Pyruvate Dehydrogenase Complex Deficiencies (PDCDs) specific database within the NAMDC Patient Data Registry
  2. Use advanced genetic analysis technologies to find mutations in those people in whom none has been found

About this Study:

This study will collect comprehensive longitudinal natural history clinical data for proven Pyruvate Dehydrogenase Complex deficiencies (PDCDs), including data about diagnoses, symptoms, and outcomes. The study will include data from patients/parents as well as medical data. The investigators will use medical records and a short questionnaire targeted to collect information about critical outcomes. This questionnaire will collect information from the subject and parent about the importance of different outcomes and allow families to discuss other outcomes that they may consider important at home. Additional details of treatment will be sought to maximize our knowledge about their effects and serve to inform future clinical trials.

Data Dictionary: On file at Data Monitoring Core Council in Cincinnati Children's Hospital Medical Center and has been provided to investigators at University Hospitals Cleveland Medical Center.

Layout table for study information
Study Type : Observational [Patient Registry]
Estimated Enrollment : 75 participants
Observational Model: Cohort
Time Perspective: Other
Target Follow-Up Duration: 5 Years
Official Title: Natural History and Advanced Genetic Study of Pyruvate Dehydrogenase Complex Deficiencies (North American Mitochondrial Disease Consortium, Rare Diseases Clinical Research Network, Project 7413)
Study Start Date : September 2015
Estimated Primary Completion Date : August 2024
Estimated Study Completion Date : August 2024


Group/Cohort Intervention/treatment
PDC Deficiency
Pyruvate Dehydrogenase Complex Deficiency Disease
Other: No intervention
This is an observational study. The investigators will collect data about exposure to responses to dietary supplements, medications, and the ketogenic diet.




Primary Outcome Measures :
  1. Survival outcomes in pyruvate dehydrogenase deficiency disease [ Time Frame: Data will be collected about duration of survival from birth until the last date known to be living at the time of data analysis. ]
    Survival will be measured in years and months.


Secondary Outcome Measures :
  1. Neurological outcomes in pyruvate dehydrogenase deficiency disease [ Time Frame: Through a participant questionnaire and retrospective review of medical records, neurological outcomes will be assessed for the entire lifetime of the participant up to the time of data collection. ]
    The number of participants with each neurological outcome will be assessed by analyzing questionnaire and medical record data. Neurological outcomes include, but are not limited to, developmental delay/intellectual disability, seizures, muscle weakness and abnormalities of tone, ataxia, neuropathy, dysautonomia, involuntary movements, microcephaly, hearing loss, and ophthalmologic abnormalities/ vision impairment.


Biospecimen Retention:   Samples With DNA
Blood sample for DNA and biochemical analysis. Saliva, buccal swab, urine sample, blood sample, or skin sample for NAMDC biorepository (optional).


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Children and adults with pyruvate dehydrogenase complex deficiency
Criteria

Inclusion Criteria:

  1. Low PDC activity in skin fibroblasts, blood lymphocytes or a muscle biopsy, below the reference range, and with valid internal controls to establish sample and assay integrity, and have had PDHA1 testing, and/or
  2. A known pathogenic mutation of a gene associated with PDC deficiency.

Relative Subjects Inclusion Criteria:

1. First or second degree relative of a primary subject for whom genetic testing indicates the presence of variants of unknown significance (VUS).

Exclusion Criteria:

  1. Another chronic neurological disease (mitochondrial or non-mitochondrial) which is not considered likely to be related to PDC deficiency.
  2. Inadequacy of needed blood or tissue sample and unwillingness or inability to submit such a sample.
  3. Unwillingness to participate in the NAMDC Patient Data Registry and Biorepository protocol.

Relative Subjects Exclusion Criteria:

1. Inadequacy of needed blood sample and unwillingness or inability to submit such a sample.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03056794


Contacts
Layout table for location contacts
Contact: Genya Kisin 216-286-9202 genya.kisin@uhhospitals.org
Contact: Jirair K. Bedoyan, MD, PhD 216-844-3936 ext 1 jirair.bedoyan@uhhospitals.org

Locations
Layout table for location information
United States, Ohio
University Hospitals Cleveland Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Principal Investigator: Jirair K. Bedoyan, MD         
Principal Investigator: Suzanne D. DeBrosse, MD, PhD         
Sub-Investigator: Douglas S. Kerr, MD, PhD         
Sponsors and Collaborators
University Hospitals Cleveland Medical Center
Rare Diseases Clinical Research Network
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Layout table for investigator information
Principal Investigator: Jirair K. Bedoyan, MD, PhD University Hospitals Cleveland Medical Center
Principal Investigator: Suzanne D. DeBrosse, MD University Hospitals Cleveland Medical Center
Additional Information:

Publications:

Layout table for additonal information
Responsible Party: Jirair K. Bedoyan, MD, PhD, Associate Professor, Department of Genetics and Genome Sciences, University Hospitals Cleveland Medical Center
ClinicalTrials.gov Identifier: NCT03056794    
Other Study ID Numbers: RDCRN 7413
5U54NS078059-05 ( U.S. NIH Grant/Contract )
First Posted: February 17, 2017    Key Record Dates
Last Update Posted: May 5, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data to be submitted to dbGap, as well as NAMDC researchers and the RDCRN.
Keywords provided by Jirair K. Bedoyan, MD, PhD, University Hospitals Cleveland Medical Center:
pyruvate
pyruvate dehydrogenase
PDC
PDCD
Additional relevant MeSH terms:
Layout table for MeSH terms
Pyruvate Dehydrogenase Complex Deficiency Disease
Deficiency Diseases
Malnutrition
Nutrition Disorders
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Metabolism, Inborn Errors
Pyruvate Metabolism, Inborn Errors
Carbohydrate Metabolism, Inborn Errors
Metabolic Diseases
Mitochondrial Diseases