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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03734263
Recruitment Status : Completed
First Posted : November 7, 2018
Last Update Posted : October 13, 2021
Sponsor:
Information provided by (Responsible Party):
Nicola Brunetti-Pierri, 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.

Condition or disease Intervention/treatment Phase
Pyruvate Dehydrogenase Complex Deficiency Drug: sodium phenylbutyrate Phase 2

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).

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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)




Primary Outcome Measures :
  1. Efficacy: blood lactate (mmol/L) [ Time Frame: two weeks after starting therapy ]
    blood lactate (mmol/L)

  2. Efficacy: blood lactate (mmol/L) [ Time Frame: four weeks after starting therapy ]
    blood lactate (mmol/L)


Secondary Outcome Measures :
  1. Efficacy: blood pyruvate (mmol/L) [ Time Frame: two weeks after starting therapy ]
    blood pyruvate (mmol/L)

  2. Efficacy:urinary lactate (mmol/mol crea) [ Time Frame: two weeks after starting therapy ]
    urinary lactate (mmol/mol crea)

  3. Efficacy: blood pyruvate (mmol/L) [ Time Frame: four weeks after starting therapy ]
    blood pyruvate (mmol/L)

  4. Efficacy: urinary lactate (mmol/mol crea) [ Time Frame: four weeks after starting therapy ]
    urinary lactate (mmol/mol crea)

  5. 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

  6. 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



Information from the National Library of Medicine

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

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.

Information from the National Library of Medicine

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


Locations
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Italy
Federico II University
Napoli, Italy, 80131
Sponsors and Collaborators
Fondazione Telethon
Publications:
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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

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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