Natural History Study of Pyruvate Dehydrogenase Deficiency

Pyruvate Dehydrogenase Complex Deficiency Clinical Trial

Official title:

Natural History Study of Pyruvate Dehydrogenase Deficiency

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05257005
• Other study ID #: 19GR12
• Secondary ID: 278183283427
• Status: Recruiting
• Start date: November 1, 2020
• Est. completion date: August 1, 2024

Study information

• Verified date: December 2023
• Source: Great Ormond Street Hospital for Children NHS Foundation Trust
• Contact: Nandaki Keshavan, MA, MB BChir
• Phone: 020 7905 2608
• Email: n.keshavan[@]ucl.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical 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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: August 1, 2024
• Est. primary completion date: August 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Pyruvate Dehydrogenase Complex Deficiency
• Pyruvate Dehydrogenase Complex Deficiency Disease

Locations

Country	Name	City	State
United Kingdom	Great Ormond Street Hospital	London

Sponsors (3)

Lead Sponsor	Collaborator
Great Ormond Street Hospital for Children NHS Foundation Trust	National Institute for Health Research, United Kingdom, The Freya Foundation

Country where clinical trial is conducted

United Kingdom, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mitochondrial Disease Phenotype	PDH deficiency Phenotype	Baseline
Other	Genetic Diagnosis	Molecular diagnosis	Baseline
Other	Medical History	Family history, past medical history	Baseline
Other	Disease timecourse	Onset, symptom debut, final outcome, follow-up.	Baseline
Other	Neuroimaging	MRI/MRS Head	Baseline
Other	Assessment of Neurophysiological outcome measures from source data	This is an observational retrospective from source data and may include the following neurophysiological measures: EMG, EEG, Nerve conduction Studies	Baseline
Other	Assessment of Cognitive and Developmental outcomes from source data	Retrospective assessments documented within source data for cognitive assessments that have occurred in the past in all patients.	Baseline
Other	Assessment of Cognitive and Developmental outcomes at baseline	For prospective component, cognitive assessments will be performed at baseline in adult patients only: Wechsler Test of Adult Reading (WTAR) test Symbol Search Speed of comprehension test	Baseline
Other	Assessment of biochemical outcome measures from source data	This is an observational retrospective from source data and may include the following biological outcome measures: EMG, EEG, Nerve conduction Studies: Blood and CSF lactate, pyruvate, amino acids, urine organic acids, PDH enzymology, OXPHOS studies, skeletal muscle histology	Baseline
Other	Management	Drug and non-drug treatments	Baseline
Primary	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.	Baseline