Pyruvate Dehydrogenase Complex Deficiency DiseaseNCT03056794
Natural History and Advanced Genetic Study of Pyruvate Dehydrogenase Complex Deficiencies
An observational study of Pyruvate Dehydrogenase Complex Deficiency Disease, run by University of Pittsburgh at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Pyruvate Dehydrogenase Complex Deficiency Disease
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2015to Dec 2030
- How long will I take part?
- 5 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Children and adults with pyruvate dehydrogenase complex deficiency
Who may be able to join
- 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
- 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).
Who cannot join
- Another chronic neurological disease (mitochondrial or non-mitochondrial) which is not considered likely to be related to PDC deficiency.
- Inadequacy of needed blood or tissue sample and unwillingness or inability to submit such a sample.
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Pittsburgh
Pittsburgh, Pennsylvania, 15260
Jirair K. Bedoyan, MD
About this study
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)
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.
Read the 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:
- Continue to add to the Pyruvate Dehydrogenase Complex Deficiencies (PDCDs) specific database within the NAMDC Patient Data Registry
- 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.
- Being tested
- No intervention
- Keywords
- pyruvate, pyruvate dehydrogenase, PDC, PDCD
- Medical subject headings
- Pyruvate Dehydrogenase Complex Deficiency Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No interventionOther
This is an observational study. The investigators will collect data about exposure to responses to dietary supplements, medications, and the ketogenic diet.
| Study group | Role | What they receive |
|---|---|---|
| PDC Deficiency | Pyruvate Dehydrogenase Complex Deficiency Disease Receives: Other: No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival outcomes in pyruvate dehydrogenase deficiency disease
Survival will be measured in years and months.
Measured: Data will be collected about duration of survival from birth until the last date known to be living at the time of data analysis.
Secondary outcomes (1)
Neurological outcomes in pyruvate dehydrogenase deficiency disease
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2017
- Study startSep 2015
- Primary completionSep 2030 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Pyruvate Dehydrogenase Complex Deficiency DiseaseStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 150 participants (estimated)
- Target duration
- 5 Years
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- Rare Diseases Clinical Research Network, National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Principal investigator, Jirair Krikor Bedoyan, University of Pittsburgh
- Investigators
- Jirair K. Bedoyan, MD, PhD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03056794
- Sponsor's protocol ID
- STUDY21090146
- Other IDs
- 5U54NS078059-05
- Status last verified
- Oct 2026
- First submitted
- 27 Jan 2017
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data to be submitted to dbGap, as well as NAMDC researchers and the RDCRN.
Publications
DeBrosse SD, Okajima K, Zhang S, Nakouzi G, Schmotzer CL, Lusk-Kopp M, Frohnapfel MB, Grahame G, Kerr DS. Spectrum of neurological and survival outcomes in pyruvate dehydrogenase complex (PDC) deficiency: lack of correlation with genotype. Mol Genet Metab. 2012 Nov;107(3):394-402. doi: 10.1016/j.ymgme.2012.09.001. Epub 2012 Sep 7.
PubMed 23021068Huang X, Bedoyan JK, Demirbas D, Harris DJ, Miron A, Edelheit S, Grahame G, DeBrosse SD, Wong LJ, Hoppel CL, Kerr DS, Anselm I, Berry GT. Succinyl-CoA synthetase (SUCLA2) deficiency in two siblings with impaired activity of other mitochondrial oxidative enzymes in skeletal muscle without mitochondrial DNA depletion. Mol Genet Metab. 2017 Mar;120(3):213-222. doi: 10.1016/j.ymgme.2016.11.005. Epub 2016 Nov 12.
PubMed 27913098Bedoyan JK, Yang SP, Ferdinandusse S, Jack RM, Miron A, Grahame G, DeBrosse SD, Hoppel CL, Kerr DS, Wanders RJA. Lethal neonatal case and review of primary short-chain enoyl-CoA hydratase (SCEH) deficiency associated with secondary lymphocyte pyruvate dehydrogenase complex (PDC) deficiency. Mol Genet Metab. 2017 Apr;120(4):342-349. doi: 10.1016/j.ymgme.2017.02.002. Epub 2017 Feb 2.
PubMed 28202214Ferdinandusse S, Friederich MW, Burlina A, Ruiter JP, Coughlin CR 2nd, Dishop MK, Gallagher RC, Bedoyan JK, Vaz FM, Waterham HR, Gowan K, Chatfield K, Bloom K, Bennett MJ, Elpeleg O, Van Hove JL, Wanders RJ. Clinical and biochemical characterization of four patients with mutations in ECHS1. Orphanet J Rare Dis. 2015 Jun 18;10:79. doi: 10.1186/s13023-015-0290-1.
PubMed 26081110Deeb KK, Bedoyan JK, Wang R, Sremba L, Schroeder MC, Grahame GJ, Boyer M, McCandless SE, Kerr DS, Zhang S. Somatic mosaicism for a novel PDHA1 mutation in a male with severe pyruvate dehydrogenase complex deficiency. Mol Genet Metab Rep. 2014 Aug 28;1:362-367. doi: 10.1016/j.ymgmr.2014.08.001. eCollection 2014.
PubMed 27896109Shin HK, Grahame G, McCandless SE, Kerr DS, Bedoyan JK. Enzymatic testing sensitivity, variability and practical diagnostic algorithm for pyruvate dehydrogenase complex (PDC) deficiency. Mol Genet Metab. 2017 Nov;122(3):61-66. doi: 10.1016/j.ymgme.2017.09.001. Epub 2017 Sep 8.
PubMed 28918066Bedoyan JK, Hecht L, Zhang S, Tarrant S, Bergin A, Demirbas D, Yang E, Shin HK, Grahame GJ, DeBrosse SD, Hoppel CL, Kerr DS, Berry GT. A novel null mutation in the pyruvate dehydrogenase phosphatase catalytic subunit gene (PDP1) causing pyruvate dehydrogenase complex deficiency. JIMD Rep. 2019 Jun 17;48(1):26-35. doi: 10.1002/jmd2.12054. eCollection 2019 Jul.
PubMed 31392110
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03056794
- Acronym / sponsor ID
- STUDY21090146
- Keywords
- pyruvate, pyruvate dehydrogenase, PDC, PDCD
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- Rare Diseases Clinical Research Network, National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Sep 2015 (actual)
- Primary completion
- Sep 2030 (estimated)
- Study completion
- Dec 2030 (estimated)
- First posted
- 17 Feb 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- Continue to add to the Pyruvate Dehydrogenase Complex Deficiencies (PDCDs) specific database within the NAMDC Patient Data Registry
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Target follow-up
- 5 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PDC Deficiency | – | Other: No interventionPyruvate Dehydrogenase Complex Deficiency Disease |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Children and adults with pyruvate dehydrogenase complex deficiency
Key inclusion criteria (4 listed)
- 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
- A known pathogenic mutation of a gene associated with PDC deficiency.
- 1. First or second degree relative of a primary subject for whom genetic testing indicates the presence of variants of unknown significance (VUS).
Key exclusion criteria (5 listed)
- Another chronic neurological disease (mitochondrial or non-mitochondrial) which is not considered likely to be related to PDC deficiency.
- Inadequacy of needed blood or tissue sample and unwillingness or inability to submit such a sample.
- Unwillingness to participate in the NAMDC Patient Data Registry and Biorepository protocol.
- 1. Inadequacy of needed blood sample and unwillingness or inability to submit such a sample.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No interventionThis is an observational study. The investigators will collect data about exposure to responses to dietary supplements, medications, and the ketogenic diet. | Other | PDC Deficiency |
Primary outcome
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.
1 secondary outcome
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2026.
- Background: PubMed 23021068DeBrosse SD, Okajima K, Zhang S, Nakouzi G, Schmotzer CL, Lusk-Kopp M, Frohnapfel MB, Grahame G, Kerr DS. Spectrum of neurological and survival outcomes in pyruvate dehydrogenase complex (PDC) deficiency: lack of correlation with genotype. Mol Genet Metab. 2012 Nov;107(3):394-402. doi: 10.1016/j.ymgme.2012.09.001. Epub 2012 Sep 7.
- Background: PubMed 27913098Huang X, Bedoyan JK, Demirbas D, Harris DJ, Miron A, Edelheit S, Grahame G, DeBrosse SD, Wong LJ, Hoppel CL, Kerr DS, Anselm I, Berry GT. Succinyl-CoA synthetase (SUCLA2) deficiency in two siblings with impaired activity of other mitochondrial oxidative enzymes in skeletal muscle without mitochondrial DNA depletion. Mol Genet Metab. 2017 Mar;120(3):213-222. doi: 10.1016/j.ymgme.2016.11.005. Epub 2016 Nov 12.
- Background: PubMed 28202214Bedoyan JK, Yang SP, Ferdinandusse S, Jack RM, Miron A, Grahame G, DeBrosse SD, Hoppel CL, Kerr DS, Wanders RJA. Lethal neonatal case and review of primary short-chain enoyl-CoA hydratase (SCEH) deficiency associated with secondary lymphocyte pyruvate dehydrogenase complex (PDC) deficiency. Mol Genet Metab. 2017 Apr;120(4):342-349. doi: 10.1016/j.ymgme.2017.02.002. Epub 2017 Feb 2.
- Background: PubMed 26081110Ferdinandusse S, Friederich MW, Burlina A, Ruiter JP, Coughlin CR 2nd, Dishop MK, Gallagher RC, Bedoyan JK, Vaz FM, Waterham HR, Gowan K, Chatfield K, Bloom K, Bennett MJ, Elpeleg O, Van Hove JL, Wanders RJ. Clinical and biochemical characterization of four patients with mutations in ECHS1. Orphanet J Rare Dis. 2015 Jun 18;10:79. doi: 10.1186/s13023-015-0290-1.
- Background: PubMed 27896109Deeb KK, Bedoyan JK, Wang R, Sremba L, Schroeder MC, Grahame GJ, Boyer M, McCandless SE, Kerr DS, Zhang S. Somatic mosaicism for a novel PDHA1 mutation in a male with severe pyruvate dehydrogenase complex deficiency. Mol Genet Metab Rep. 2014 Aug 28;1:362-367. doi: 10.1016/j.ymgmr.2014.08.001. eCollection 2014.
- Background: PubMed 28918066Shin HK, Grahame G, McCandless SE, Kerr DS, Bedoyan JK. Enzymatic testing sensitivity, variability and practical diagnostic algorithm for pyruvate dehydrogenase complex (PDC) deficiency. Mol Genet Metab. 2017 Nov;122(3):61-66. doi: 10.1016/j.ymgme.2017.09.001. Epub 2017 Sep 8.
- Background: PubMed 31392110Bedoyan JK, Hecht L, Zhang S, Tarrant S, Bergin A, Demirbas D, Yang E, Shin HK, Grahame GJ, DeBrosse SD, Hoppel CL, Kerr DS, Berry GT. A novel null mutation in the pyruvate dehydrogenase phosphatase catalytic subunit gene (PDP1) causing pyruvate dehydrogenase complex deficiency. JIMD Rep. 2019 Jun 17;48(1):26-35. doi: 10.1002/jmd2.12054. eCollection 2019 Jul.
- Individual participant dataSharing planned: Yes. Data to be submitted to dbGap, as well as NAMDC researchers and the RDCRN.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jirair K. Bedoyan, MD, PhD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pyruvate Dehydrogenase Complex Deficiency Disease, run by University of Pittsburgh at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jirair K Bedoyan, MD, PhD (412-692-7594, bedoyanjk@upmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03056794, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2026.