This is a phase II, multicenter, prospective, non-comparative clinical trial to assess the efficacy and safety of the treatment of pyruvate dehydrogenase deficiency (PDH) patients with glycerol phenylbutyrate (Ravicti®).
The trial will be conducted with three visits: 3 day hospitalizations including clinical consultations and paramedical procedures at Month 0 (M0), Month 3 (M3), Month 6 (M6).
During all the research, AE/SAE and treatment compliance will be recorded. Patients will keep their usual treatment during the study time: vitamin B1, ketogenic diet, possible anti-epileptic and/or dystonic treatment(s).
The efficacy on fatigue, polyhandicap, neurodevelopmental functioning, quality of life and seizure amount for epileptic patients will be evaluated at 0, 3 and 6 months. Biological balance will be assed with regular quantification of PDH deficiency markers, lactate concentration and amino acid plasma quantification.
Child from 2 to 17 years of age Or
Adult from 18 to 25 years of age
a class 4 or 5- missense variant on the PDHA1 gene or
one homozygous variant or two mixed heterozygous variants of class 4 or 5 that are missense variants on PDHB or DLAT genes or
Patient with E3 deficiency due to pathogenic mutation in DLD gene
Patient with non-sense mutation on PDHB or DLAT gene, and male patient with non-sense mutation or PDHA1 gene.
Patient with planned hip or scoliosos surgery during the study timeframe.
Patient whose parents / legal representative refuse flu vaccine.
Single group
Glycerol Phenylbutyrate 1100 MG/ML [Ravicti]
DrugThe patients will orally take a dose of 200 mg/kg/day three times a day during meals: breakfast, lunch or afternoon snack and diner for 6 months.
Efficacy on fatigue at 6 months
The efficacy of Glycerol Phenylbutyrate treatment on fatigue at 6 months will be evaluated by the Pediatric Quality of Life Multidimensional Fatigue Scale (PedsQL MFS) at Month 0 and Month 6. Results range from 0 to 72.
Efficacy on fatigue at 3 months
The efficacy of Glycerol Phenylbutyrate treatment on fatigue at 3 months will be evaluated by the Pediatric Quality of Life Multidimensional Fatigue Scale (PedsQL MFS) at Month 0 and Month 3. Results range from 0 to 72.
Efficacy on polyhandicap
The efficacy of Glycerol Phenylbutyrate treatment on polyhandicap, will be evaluated by the Polyhandicap severity scale at Month 0 and Month 6, performed by a psychomotrician, a physiotherapist or a medical physician. Results range from 0 to 93.
Efficacy on neurodevelopmental functioning
The efficacy of Glycerol Phenylbutyrate treatment on neurodevelopmental functions will be evaluated by a semi-structured interview with the Vineland Adaptive Behavior Scales second edition (VABS-II) 20 at Month 0 and Month 6. Results range from 0 to 160.
Efficacy on epilepsy
The efficacy of Glycerol Phenylbutyrate treatment on the number of seizures during the last 3 months using patient diary, and electroencephalogram (EEG) for epileptic patients at Month 6 compared to Month 0.
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Assistance Publique - Hôpitaux de Paris
Lead sponsor
URC-CIC Paris Descartes Necker Cochin
Collaborator
