Use of Phenylbutyrate Therapy for Patients With Pyruvate Dehydrogenase Complex Deficiency. (TIGEM2-PDH)
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ClinicalTrials.gov Identifier: NCT03734263 |
Recruitment Status :
Completed
First Posted : November 7, 2018
Last Update Posted : October 13, 2021
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Pyruvate Dehydrogenase Complex Deficiency | Drug: sodium phenylbutyrate | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 1 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Intervention Model Description: | An open-label, uncontrolled, multicentric clinical trial will be performed on pediatric patients with PDC deficiency. Enrolled subjects will receive a four-week period of treatment with NaPB; primary and secondary endpoints will be evaluated at defined time points. Before NaPB treatment, all patients will undergo a four-week period of observation during which the same parameters will be analyzed at different time points, with the aim of evaluating basal conditions in the absence of treatment. |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Pilot Clinical Trial to Investigate the Safety and Efficacy of Phenylbutyrate Therapy for Patients With Pyruvate Dehydrogenase Complex Deficiency. |
Actual Study Start Date : | October 1, 2018 |
Actual Primary Completion Date : | July 30, 2019 |
Actual Study Completion Date : | December 30, 2020 |

Arm | Intervention/treatment |
---|---|
Experimental: open label
sodium phenylbutyrate
|
Drug: sodium phenylbutyrate
Enrolled subjects will receive a four-week period of treatment with sodium phenylbutyrate (oral use) |
- Efficacy: blood lactate (mmol/L) [ Time Frame: two weeks after starting therapy ]blood lactate (mmol/L)
- Efficacy: blood lactate (mmol/L) [ Time Frame: four weeks after starting therapy ]blood lactate (mmol/L)
- Efficacy: blood pyruvate (mmol/L) [ Time Frame: two weeks after starting therapy ]blood pyruvate (mmol/L)
- Efficacy:urinary lactate (mmol/mol crea) [ Time Frame: two weeks after starting therapy ]urinary lactate (mmol/mol crea)
- Efficacy: blood pyruvate (mmol/L) [ Time Frame: four weeks after starting therapy ]blood pyruvate (mmol/L)
- Efficacy: urinary lactate (mmol/mol crea) [ Time Frame: four 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 [ Time Frame: 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 [ Time Frame: four weeks after starting therapy ]Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

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Ages Eligible for Study: | 3 Months to 18 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03734263
Italy | |
Federico II University | |
Napoli, Italy, 80131 |
Responsible Party: | Nicola Brunetti-Pierri, Principal Investigator, Fondazione Telethon |
ClinicalTrials.gov Identifier: | NCT03734263 |
Other Study ID Numbers: |
TIGEM2-PDH |
First Posted: | November 7, 2018 Key Record Dates |
Last Update Posted: | October 13, 2021 |
Last Verified: | October 2021 |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Pyruvate Dehydrogenase Complex Deficiency Disease Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Brain Diseases Central Nervous System Diseases Nervous System Diseases Mental Retardation, X-Linked Intellectual Disability Neurobehavioral Manifestations Neurologic Manifestations |
Genetic Diseases, X-Linked Genetic Diseases, Inborn Heredodegenerative Disorders, Nervous System Metabolism, Inborn Errors Pyruvate Metabolism, Inborn Errors Carbohydrate Metabolism, Inborn Errors Metabolic Diseases Mitochondrial Diseases 4-phenylbutyric acid Antineoplastic Agents |