Natural History Study of Pyruvate Dehydrogenase Deficiency

Sponsor

Great Ormond Street Hospital for Children NHS Foundation Trust (Other)

Overall Status

Recruiting

CT.gov ID

NCT05257005

Collaborator

The Freya Foundation (Other), National Institute for Health Research, United Kingdom (Other)

Enrollment

Location

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pyruvate Dehydrogenase Complex Deficiency Pyruvate Dehydrogenase E1 Alpha Deficiency Pyruvate Dehydrogenase E1-Beta Deficiency Pyruvate Dehydrogenase E2 Deficiency Pyruvate Dehydrogenase Phosphatase Deficiency

Study Design

Study Type:

Observational

Anticipated Enrollment :

50 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Natural History Study of Pyruvate Dehydrogenase Deficiency

Actual Study Start Date :

Nov 1, 2020

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Patient cohort Non interventional study

Outcome Measures

Primary Outcome Measures

Newcastle Mitochondrial Disease Scale [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.

Other Outcome Measures

Mitochondrial Disease Phenotype [Baseline]
PDH deficiency Phenotype
Genetic Diagnosis [Baseline]
Molecular diagnosis
Medical History [Baseline]
Family history, past medical history
Disease timecourse [Baseline]
Onset, symptom debut, final outcome, follow-up.
Neuroimaging [Baseline]
MRI/MRS Head
Assessment of Neurophysiological outcome measures from source data [Baseline]
This is an observational retrospective from source data and may include the following neurophysiological measures: EMG, EEG, Nerve conduction Studies
Assessment of Cognitive and Developmental outcomes from source data [Baseline]
Retrospective assessments documented within source data for cognitive assessments that have occurred in the past in all patients.
Assessment of Cognitive and Developmental outcomes at baseline [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
Assessment of biochemical outcome measures from source data [Baseline]
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
Management [Baseline]
Drug and non-drug treatments

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.