Use of Phenylbutyrate Therapy for Patients With Pyruvate Dehydrogenase Complex Deficiency.
Phase 2
Completed
- Conditions
- Pyruvate Dehydrogenase Complex Deficiency
- Interventions
- Registration Number
- NCT03734263
- Lead Sponsor
- Fondazione Telethon
- Brief Summary
In this study phenylbutyrate is used for patients with pyruvate dehydrogenase complex deficiency. The aim of the study is to investigate the safety and efficacy of therapy.
- Detailed Description
The Investigator will evaluate the safety and efficacy of a 4-weeks treatment with sodium phenylbutyrate in patients with pyruvate dehydrogenase complex deficiency. Efficacy will be evaluated based on biochemical endpoints (blood lactate and pyruvate).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1
Inclusion Criteria
- Subject must be older than 3 months old and younger than 18 years old.
- Clinical diagnosis of PDC deficiency confirmed by DNA testing showing a missense mutation in the PDHA1 gene.
- Lactate concentration ≥ 2.5 mmol/l or ≥ 2 mmol/l, respectively in venous or arterial blood samples.
- Provision of signed and dated informed consent form by the parents/legal guardians of the patient
- Negative pregnancy test for women of childbearing potential, and agree to use effective form of contraception until 6 weeks post treatment.
Exclusion Criteria
- Frameshift or nonsense mutations of the PDHA1 gene.
- Defects affecting any gene encoding PDC subunits other than PDHA1
- Secondary forms of lactic acidosis (e.g. impaired oxygenation or circulation).
- Tracheostomy or requirement for artificial ventilation.
- Hyperlactatemia or organic acidosis associated with other metabolic disorders (e.g. biotinidase deficiency, primary disorders of gluconeogenesis, organic acidurias, primary defects of fatty acids oxidation)
- Evidence of hepatic insufficiency, renal insufficiency, edema with sodium retention, cardiac arrhythmia, congenital heart defects, hypertension, blood dyscrasia, symptomatic pancreatitis, or inflammatory bowel disease.
- Any clinical condition or medications known to significantly affect renal clearance.
- Any other condition that, in the opinion of the Investigator, may compromise the safety or compliance of the patient or would preclude the patient from successful completion of the study.
- Known allergic reactions to components of the study agent.
- Treatment with another investigational drug or other intervention (including DCA) or participation in a clinical study with an investigational drug within 6 months prior to enrolment.
- Pregnancy or lactation.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description open label sodium phenylbutyrate sodium phenylbutyrate
- Primary Outcome Measures
Name Time Method Efficacy: blood lactate (mmol/L) four weeks after starting therapy blood lactate (mmol/L)
- Secondary Outcome Measures
Name Time Method Efficacy: urinary lactate (mmol/mol crea) four weeks after starting therapy urinary lactate (mmol/mol crea)
Efficacy: blood pyruvate (mmol/L) four weeks after starting therapy blood pyruvate (mmol/L)
Efficacy:urinary lactate (mmol/mol crea) two weeks after starting therapy urinary lactate (mmol/mol crea)
Safety and tolerability:Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 two weeks after starting therapy Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Safety and tolerability: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 four weeks after starting therapy Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Trial Locations
- Locations (1)
Federico II University
🇮🇹Napoli, Italy