Natural History Study of Pyruvate Dehydrogenase Deficiency

NCT05257005 | Unknown

• 3 other identifiers: 19GR12278183283427
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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

Other Outcomes (10)

• Mitochondrial Disease Phenotype

  Baseline

• Genetic Diagnosis

  Baseline

• Medical History

  Baseline

Study Arms (1)

Patient cohort

Non interventional study

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• Compatible clinical history AND
• a Enzymatic confirmation demonstrating reduced PDH activity in patient cells or muscle tissue OR
• b Confirmed pathogenic mutation in a gene associated with primary PDH deficiency (PDHA1, PDHB, PDHX, PDP1, DLAT) OR
• c First degree relative with a confirmed pathogenic mutation causing primary PDH deficiency

You may not qualify if:

• 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.

Sponsors & Collaborators

• Great Ormond Street Hospital for Children NHS Foundation Trust: lead
• The Freya Foundation: collaborator
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (1)

Great Ormond Street Hospital

London, United Kingdom

RECRUITING

Related Publications (2)

• 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.

  PMID: 17123819 BACKGROUND

• 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.

  PMID: 22896851 BACKGROUND

MeSH Terms

Conditions

Pyruvate Dehydrogenase Complex Deficiency Disease; Pyruvate Dehydrogenase E1 Alpha Deficiency; Pyruvate Dehydrogenase E1-Beta Deficiency; Pyruvate Dehydrogenase E2 Deficiency; Pyruvate dehydrogenase phosphatase deficiency

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Metabolism, Inborn Errors; Pyruvate Metabolism, Inborn Errors; Carbohydrate Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Mitochondrial Diseases

Study Officials

• Shamima Rahman, PhD

  Great Ormond Street Hospital NHS Foundation Trust

  STUDY DIRECTOR

Central Study Contacts

Nandaki Keshavan, MA, MB BChir

CONTACT

020 7905 2608; n.keshavan@ucl.ac.uk

Vanshree Patel, PhD

CONTACT

0207 905 42271; vanshree.patel@gosh.nhs.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2022
• First Posted: February 25, 2022
• Study Start: November 1, 2020
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: December 5, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)