Ignite Creation Date:
2025-12-25 @ 3:23 AM
Ignite Modification Date:
2025-12-26 @ 2:01 AM
Study NCT ID:
NCT05257005
Status:
RECRUITING
Last Update Posted:
2023-12-05
First Post:
2022-02-02
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Natural History Study of Pyruvate Dehydrogenase Deficiency
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015325', 'term': 'Pyruvate Dehydrogenase Complex Deficiency Disease'}, {'id': 'C564071', 'term': 'Pyruvate Dehydrogenase E1 Alpha Deficiency'}, {'id': 'C566729', 'term': 'Pyruvate Dehydrogenase E1-Beta Deficiency'}, {'id': 'C565448', 'term': 'Pyruvate Dehydrogenase E2 Deficiency'}, {'id': 'C536258', 'term': 'Pyruvate dehydrogenase phosphatase deficiency'}], 'ancestors': [{'id': 'D020739', 'term': 'Brain Diseases, Metabolic, Inborn'}, {'id': 'D001928', 'term': 'Brain Diseases, Metabolic'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D038901', 'term': 'X-Linked Intellectual Disability'}, {'id': 'D008607', 'term': 'Intellectual Disability'}, {'id': 'D019954', 'term': 'Neurobehavioral Manifestations'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D040181', 'term': 'Genetic Diseases, X-Linked'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D020271', 'term': 'Heredodegenerative Disorders, Nervous System'}, {'id': 'D008661', 'term': 'Metabolism, Inborn Errors'}, {'id': 'D015323', 'term': 'Pyruvate Metabolism, Inborn Errors'}, {'id': 'D002239', 'term': 'Carbohydrate Metabolism, Inborn Errors'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D028361', 'term': 'Mitochondrial Diseases'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 50}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2020-11-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-12', 'completionDateStruct': {'date': '2024-08-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2023-12-04', 'studyFirstSubmitDate': '2022-02-02', 'studyFirstSubmitQcDate': '2022-02-16', 'lastUpdatePostDateStruct': {'date': '2023-12-05', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2022-02-25', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-08-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Mitochondrial Disease Phenotype', 'timeFrame': 'Baseline', 'description': 'PDH deficiency Phenotype'}, {'measure': 'Genetic Diagnosis', 'timeFrame': 'Baseline', 'description': 'Molecular diagnosis'}, {'measure': 'Medical History', 'timeFrame': 'Baseline', 'description': 'Family history, past medical history'}, {'measure': 'Disease timecourse', 'timeFrame': 'Baseline', 'description': 'Onset, symptom debut, final outcome, follow-up.'}, {'measure': 'Neuroimaging', 'timeFrame': 'Baseline', 'description': 'MRI/MRS Head'}, {'measure': 'Assessment of Neurophysiological outcome measures from source data', 'timeFrame': 'Baseline', 'description': 'This is an observational retrospective from source data and may include the following neurophysiological measures: EMG, EEG, Nerve conduction Studies'}, {'measure': 'Assessment of Cognitive and Developmental outcomes from source data', 'timeFrame': 'Baseline', 'description': 'Retrospective assessments documented within source data for cognitive assessments that have occurred in the past in all patients.'}, {'measure': 'Assessment of Cognitive and Developmental outcomes at baseline', 'timeFrame': 'Baseline', 'description': 'For prospective component, cognitive assessments will be performed at baseline in adult patients only:\n\nWechsler Test of Adult Reading (WTAR) test Symbol Search Speed of comprehension test'}, {'measure': 'Assessment of biochemical outcome measures from source data', 'timeFrame': 'Baseline', 'description': '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'}, {'measure': 'Management', 'timeFrame': 'Baseline', 'description': 'Drug and non-drug treatments'}], 'primaryOutcomes': [{'measure': 'Newcastle Mitochondrial Disease Scale', 'timeFrame': 'Baseline', 'description': '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.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['PDH deficiency', 'Natural History', 'Outcomes', 'Prognosis', 'Genotype-phenotype correlation', 'Quality of life', 'Outcome measures'], 'conditions': ['Pyruvate Dehydrogenase Complex Deficiency', 'Pyruvate Dehydrogenase E1 Alpha Deficiency', 'Pyruvate Dehydrogenase E1-Beta Deficiency', 'Pyruvate Dehydrogenase E2 Deficiency', 'Pyruvate Dehydrogenase Phosphatase Deficiency']}, 'referencesModule': {'references': [{'pmid': '17123819', 'type': 'BACKGROUND', '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.'}, {'pmid': '22896851', 'type': 'BACKGROUND', '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."}]}, 'descriptionModule': {'briefSummary': '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.\n\nThe 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Children and Adults with a diagnosis of (primary) Pyruvate Dehydrogenase Deficiency who are recruited from the community via tertiary healthcare services', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n1. Compatible clinical history AND\n\n2a Enzymatic confirmation demonstrating reduced PDH activity in patient cells or muscle tissue OR\n\n2b Confirmed pathogenic mutation in a gene associated with primary PDH deficiency (PDHA1, PDHB, PDHX, PDP1, DLAT) OR\n\n2c First degree relative with a confirmed pathogenic mutation causing primary PDH deficiency\n\nExclusion Criteria:\n\nPatients 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."}, 'identificationModule': {'nctId': 'NCT05257005', 'briefTitle': 'Natural History Study of Pyruvate Dehydrogenase Deficiency', 'organization': {'class': 'OTHER', 'fullName': 'Great Ormond Street Hospital for Children NHS Foundation Trust'}, 'officialTitle': 'Natural History Study of Pyruvate Dehydrogenase Deficiency', 'orgStudyIdInfo': {'id': '19GR12'}, 'secondaryIdInfos': [{'id': '278183', 'type': 'OTHER', 'domain': 'Health Research Authority, United Kingdom'}, {'id': '283427', 'type': 'OTHER', 'domain': 'Health Research Authority, United Kingdom'}]}, 'armsInterventionsModule': {'armGroups': [{'label': 'Patient cohort', 'description': 'Non interventional study'}]}, 'contactsLocationsModule': {'locations': [{'city': 'London', 'status': 'RECRUITING', 'country': 'United Kingdom', 'contacts': [{'name': 'Shamima Rahman, PhD', 'role': 'CONTACT', 'email': 'shamima.rahman@gosh.nhs.uk'}, {'name': 'Shamima Rahman, PhD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Great Ormond Street Hospital', 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}], 'centralContacts': [{'name': 'Nandaki Keshavan, MA, MB BChir', 'role': 'CONTACT', 'email': 'n.keshavan@ucl.ac.uk', 'phone': '020 7905 2608'}, {'name': 'Vanshree Patel, PhD', 'role': 'CONTACT', 'email': 'vanshree.patel@gosh.nhs.uk', 'phone': '0207 905 42271'}], 'overallOfficials': [{'name': 'Shamima Rahman, PhD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Great Ormond Street Hospital NHS Foundation Trust'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Great Ormond Street Hospital for Children NHS Foundation Trust', 'class': 'OTHER'}, 'collaborators': [{'name': 'The Freya Foundation', 'class': 'UNKNOWN'}, {'name': 'National Institute for Health Research, United Kingdom', 'class': 'OTHER_GOV'}], 'responsibleParty': {'type': 'SPONSOR'}}}}