Use of Phenylbutyrate Therapy for Patients With Pyruvate Dehydrogenase Complex Deficiency. (TIGEM2-PDH)

Fondazione Telethon

Status and phase: Completed; Phase 2

Conditions: Pyruvate Dehydrogenase Complex Deficiency

Treatments: Drug: sodium phenylbutyrate

Study type: Interventional

Funder types: Other

Identifiers

NCT03734263

TIGEM2-PDH

Details and patient eligibility

About

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.

Full 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).

Enrollment: 1 patient

Sex: All

Ages: 3 months to 18 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Subject must be older than 3 months old and younger than 18 years old.
2. Clinical diagnosis of PDC deficiency confirmed by DNA testing showing a missense mutation in the PDHA1 gene.
3. Lactate concentration ≥ 2.5 mmol/l or ≥ 2 mmol/l, respectively in venous or arterial blood samples.
4. Provision of signed and dated informed consent form by the parents/legal guardians of the patient
5. Negative pregnancy test for women of childbearing potential, and agree to use effective form of contraception until 6 weeks post treatment.

Exclusion criteria

1. Frameshift or nonsense mutations of the PDHA1 gene.
2. Defects affecting any gene encoding PDC subunits other than PDHA1
3. Secondary forms of lactic acidosis (e.g. impaired oxygenation or circulation).
4. Tracheostomy or requirement for artificial ventilation.
5. 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)
6. Evidence of hepatic insufficiency, renal insufficiency, edema with sodium retention, cardiac arrhythmia, congenital heart defects, hypertension, blood dyscrasia, symptomatic pancreatitis, or inflammatory bowel disease.
7. Any clinical condition or medications known to significantly affect renal clearance.
8. 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.
9. Known allergic reactions to components of the study agent.
10. 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.
11. Pregnancy or lactation.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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1 participants in 1 patient group

open label

Experimental group

Description:

sodium phenylbutyrate

Treatment:

Drug: sodium phenylbutyrate