Pyruvate Dehydrogenase Complex DeficiencyNCT05257005
Natural History Study of Pyruvate Dehydrogenase Deficiency
An observational study of Pyruvate Dehydrogenase Complex Deficiency and Pyruvate Dehydrogenase E1 Alpha Deficiency, run by Great Ormond Street Hospital for Children NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Pyruvate dehydrogenase (PDH) deficiency is one of the most common mitochondrial disorders. Patients with this genetic condition have difficulty utilising carbohydrates to produce energy and develop a combination of problems including seizures, poor balance, developmental delay, disability and have a reduced life… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Pyruvate Dehydrogenase Complex Deficiency, Pyruvate Dehydrogenase E1 Alpha Deficiency, Pyruvate Dehydrogenase E1-Beta Deficiency
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Nov 2020to 1 Aug 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
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 a diagnosis of (primary) Pyruvate Dehydrogenase Deficiency who are recruited from the community via tertiary healthcare services
Who may be able to join
- Compatible clinical history AND
- 2a Enzymatic confirmation demonstrating reduced PDH activity in patient cells or muscle tissue OR
- 2b Confirmed pathogenic mutation in a gene associated with primary PDH deficiency (PDHA1, PDHB, PDHX, PDP1, DLAT) OR
- 2c First degree relative with a confirmed pathogenic mutation causing primary PDH deficiency
Who cannot join
- Patients with 'secondary PDH deficiency' that is patients who meet criteria 1 and 2a but who have received a genetic diagnosis which confirms pathogenic variants in a gene not associated with primary PDH deficiency.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Great Ormond Street Hospital
London
Shamima Rahman, PhD, shamima.rahman@gosh.nhs.uk
Shamima Rahman, PhD
About this study
Pyruvate dehydrogenase (PDH) deficiency is one of the most common mitochondrial disorders. Patients with this genetic condition have difficulty utilising carbohydrates to produce energy and develop a combination of problems including seizures, poor balance, developmental delay, disability and have a reduced life expectancy. As for most mitochondrial disorders there is a lack of effective treatments. It is essential to understand the mechanisms underlying the disease in order to identify new treatments, and to understand the natural history of disease in order to prepare for clinical trials. To date, a natural history study of PDH deficiency has not been undertaken in the UK.
The researchers aim to undertake the first natural history study of PDH deficiency in the UK, to describe the spectrum of symptoms, genetics, management and outcomes in both children and adult patients.
- Conditions
- Pyruvate Dehydrogenase Complex Deficiency, Pyruvate Dehydrogenase E1 Alpha Deficiency, Pyruvate Dehydrogenase E1-Beta Deficiency, Pyruvate Dehydrogenase E2 Deficiency, Pyruvate Dehydrogenase Phosphatase Deficiency
- Keywords
- PDH deficiency, Natural History, Outcomes, Prognosis, Genotype-phenotype correlation, Quality of life, Outcome measures
- Medical subject headings
- Pyruvate Dehydrogenase Complex Deficiency Disease, Pyruvate Dehydrogenase E1 Alpha Deficiency, Pyruvate Dehydrogenase E1-Beta Deficiency, Pyruvate Dehydrogenase E2 Deficiency, Pyruvate dehydrogenase phosphatase deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patient cohort | Non interventional study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Newcastle Mitochondrial Disease Scale
Newcastle Paediatric and Adult Mitochondrial Disease Scale This is a validated scoring system for mitochondrial disease patients and measures severity of disease using multiple different clinical outcome measures and questionnaires. A higher score indicates greater disease severity.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2022
- Study start1 Nov 2020
- Primary completion1 Aug 2024 (estimated)
- Study completion1 Aug 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pyruvate Dehydrogenase Complex DeficiencyStudies of the same condition, open and under way.
- 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
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Great Ormond Street Hospital for Children NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- The Freya Foundation, National Institute for Health Research, United Kingdom
- Responsible party
- Sponsor
- Investigators
- Shamima Rahman, PhD, Study director, Great Ormond Street Hospital NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05257005
- Sponsor's protocol ID
- 19GR12
- Other IDs
- 278183, 283427
- Status last verified
- Dec 2023
- First submitted
- 2 Feb 2022
- Last updated
- 5 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Phoenix C, Schaefer AM, Elson JL, Morava E, Bugiani M, Uziel G, Smeitink JA, Turnbull DM, McFarland R. A scale to monitor progression and treatment of mitochondrial disease in children. Neuromuscul Disord. 2006 Dec;16(12):814-20. doi: 10.1016/j.nmd.2006.08.006. Epub 2006 Nov 22.
PubMed 17123819Patel KP, O'Brien TW, Subramony SH, Shuster J, Stacpoole PW. The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients. Mol Genet Metab. 2012 Jul;106(3):385-94. doi: 10.1016/j.ymgme.2012.03.017.
PubMed 22896851
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natural History Study of Pyruvate Dehydrogenase Deficiency
- ClinicalTrials.gov ID
- NCT05257005
- Acronym / sponsor ID
- 19GR12
- Conditions
- Pyruvate Dehydrogenase Complex Deficiency, Pyruvate Dehydrogenase E1 Alpha Deficiency, Pyruvate Dehydrogenase E1-Beta Deficiency, Pyruvate Dehydrogenase E2 Deficiency, Pyruvate Dehydrogenase Phosphatase Deficiency
- Keywords
- PDH deficiency, Natural History, Outcomes, Prognosis, Genotype-phenotype correlation, Quality of life, Outcome measures
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Great Ormond Street Hospital for Children NHS Foundation TrustUniversity, hospital or other
- Collaborators
- The Freya Foundation, National Institute for Health Research, United Kingdom
- Study start
- 1 Nov 2020 (actual)
- Primary completion
- 1 Aug 2024 (estimated)
- Study completion
- 1 Aug 2024 (estimated)
- First posted
- 25 Feb 2022 (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.
Pyruvate dehydrogenase (PDH) deficiency is one of the most common mitochondrial disorders. Patients with this genetic condition have difficulty utilising carbohydrates to produce energy and develop a combination of problems including seizures, poor balance, developmental delay, disability and have a reduced life expectancy. As for most mitochondrial disorders there is a lack of effective treatments. It is essential to understand the mechanisms underlying the disease in order to identify new treatments, and to understand the natural history of disease in order to prepare for clinical trials. To date, a natural history study of PDH deficiency has not been undertaken in the UK.
The researchers aim to undertake the first natural history study of PDH deficiency in the UK, to describe the spectrum of symptoms, genetics, management and outcomes in both children and adult patients.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patient cohort | – | –Non interventional study |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Children and Adults with a diagnosis of (primary) Pyruvate Dehydrogenase Deficiency who are recruited from the community via tertiary healthcare services
Key inclusion criteria (4 listed)
- Compatible clinical history AND
- 2a Enzymatic confirmation demonstrating reduced PDH activity in patient cells or muscle tissue OR
- 2b Confirmed pathogenic mutation in a gene associated with primary PDH deficiency (PDHA1, PDHB, PDHX, PDP1, DLAT) OR
- 2c First degree relative with a confirmed pathogenic mutation causing primary PDH deficiency
Key exclusion criteria (1 listed)
- Patients with 'secondary PDH deficiency' that is patients who meet criteria 1 and 2a but who have received a genetic diagnosis which confirms pathogenic variants in a gene not associated with primary PDH deficiency.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Newcastle Mitochondrial Disease Scale
Time frame: Baseline
Newcastle Paediatric and Adult Mitochondrial Disease Scale This is a validated scoring system for mitochondrial disease patients and measures severity of disease using multiple different clinical outcome measures and questionnaires. A higher score indicates greater disease severity.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2023.
- Background: PubMed 17123819Phoenix C, Schaefer AM, Elson JL, Morava E, Bugiani M, Uziel G, Smeitink JA, Turnbull DM, McFarland R. A scale to monitor progression and treatment of mitochondrial disease in children. Neuromuscul Disord. 2006 Dec;16(12):814-20. doi: 10.1016/j.nmd.2006.08.006. Epub 2006 Nov 22.
- Background: PubMed 22896851Patel KP, O'Brien TW, Subramony SH, Shuster J, Stacpoole PW. The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients. Mol Genet Metab. 2012 Jul;106(3):385-94. doi: 10.1016/j.ymgme.2012.03.017.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Shamima Rahman, PhD study director
Great Ormond Street Hospital NHS Foundation Trust
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 and Pyruvate Dehydrogenase E1 Alpha Deficiency, run by Great Ormond Street Hospital for Children NHS Foundation Trust at 1 site in United Kingdom.
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 1 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: status not confirmed, as of the sponsor's last update on 5 Dec 2023. 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 Kingdom. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nandaki Keshavan, MA, MB BChir (020 7905 2608, n.keshavan@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Newcastle Mitochondrial Disease Scale (time frame: Baseline). 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 NCT05257005, which also lists 2 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 Dec 2023.