Clinical trial NCT05257005: Natural History Study of Pyruvate Dehydrogenase Deficiency
Official title: Natural History Study of Pyruvate Dehydrogenase Deficiency
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Lead sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: The Freya Foundation
name: National Institute for Health Research, United Kingdom
First posted: 2022-02-25
Enrollment: 50
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children and Adults with a diagnosis of (primary) Pyruvate Dehydrogenase Deficiency who are recruited from the community via tertiary healthcare services

Brief 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 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.


Eligibility criteria: Inclusion Criteria:

1. 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

Exclusion Criteria:

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.

Primary outcomes:
measure: Newcastle Mitochondrial Disease Scale
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
measure: Mitochondrial Disease Phenotype
timeFrame: Baseline
measure: Genetic Diagnosis
timeFrame: Baseline
measure: Medical History
timeFrame: Baseline
measure: Disease timecourse
timeFrame: Baseline
measure: Neuroimaging
timeFrame: Baseline
measure: Assessment of Neurophysiological outcome measures from source data
timeFrame: Baseline
measure: Assessment of Cognitive and Developmental outcomes from source data
timeFrame: Baseline
measure: Assessment of Cognitive and Developmental outcomes at baseline
timeFrame: Baseline
measure: Assessment of biochemical outcome measures from source data
timeFrame: Baseline
measure: Management
timeFrame: Baseline
Locations:
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
Study officials:
affiliation: Great Ormond Street Hospital NHS Foundation Trust
name: Shamima Rahman, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Patel 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.