- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03734263
Use of Phenylbutyrate Therapy for Patients With Pyruvate Dehydrogenase Complex Deficiency. (TIGEM2-PDH)
October 5, 2021 updated by: Nicola Brunetti-Pierri, Fondazione Telethon
Pilot Clinical Trial to Investigate the Safety and Efficacy of Phenylbutyrate Therapy for Patients With Pyruvate Dehydrogenase Complex Deficiency.
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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).
Study Type
Interventional
Enrollment (Actual)
1
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Napoli, Italy, 80131
- Federico II University
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
3 months to 18 years (Child, Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: open label
sodium phenylbutyrate
|
Enrolled subjects will receive a four-week period of treatment with sodium phenylbutyrate (oral use)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Efficacy: blood lactate (mmol/L)
Time Frame: two weeks after starting therapy
|
blood lactate (mmol/L)
|
two weeks after starting therapy
|
Efficacy: blood lactate (mmol/L)
Time Frame: four weeks after starting therapy
|
blood lactate (mmol/L)
|
four weeks after starting therapy
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Efficacy: blood pyruvate (mmol/L)
Time Frame: two weeks after starting therapy
|
blood pyruvate (mmol/L)
|
two weeks after starting therapy
|
Efficacy:urinary lactate (mmol/mol crea)
Time Frame: two weeks after starting therapy
|
urinary lactate (mmol/mol crea)
|
two weeks after starting therapy
|
Efficacy: blood pyruvate (mmol/L)
Time Frame: four weeks after starting therapy
|
blood pyruvate (mmol/L)
|
four weeks after starting therapy
|
Efficacy: urinary lactate (mmol/mol crea)
Time Frame: four weeks after starting therapy
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urinary lactate (mmol/mol crea)
|
four weeks after starting therapy
|
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
|
two weeks after starting therapy
|
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
|
four weeks after starting therapy
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Ferriero R, Manco G, Lamantea E, Nusco E, Ferrante MI, Sordino P, Stacpoole PW, Lee B, Zeviani M, Brunetti-Pierri N. Phenylbutyrate therapy for pyruvate dehydrogenase complex deficiency and lactic acidosis. Sci Transl Med. 2013 Mar 6;5(175):175ra31. doi: 10.1126/scitranslmed.3004986.
- Ferriero R, Brunetti-Pierri N. Phenylbutyrate increases activity of pyruvate dehydrogenase complex. Oncotarget. 2013 Jun;4(6):804-5. doi: 10.18632/oncotarget.1000. No abstract available.
- Ferriero R, Boutron A, Brivet M, Kerr D, Morava E, Rodenburg RJ, Bonafe L, Baumgartner MR, Anikster Y, Braverman NE, Brunetti-Pierri N. Phenylbutyrate increases pyruvate dehydrogenase complex activity in cells harboring a variety of defects. Ann Clin Transl Neurol. 2014 Jul;1(7):462-70. doi: 10.1002/acn3.73. Epub 2014 Jun 19.
- Ferriero R, Iannuzzi C, Manco G, Brunetti-Pierri N. Differential inhibition of PDKs by phenylbutyrate and enhancement of pyruvate dehydrogenase complex activity by combination with dichloroacetate. J Inherit Metab Dis. 2015 Sep;38(5):895-904. doi: 10.1007/s10545-014-9808-2. Epub 2015 Jan 20.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 1, 2018
Primary Completion (Actual)
July 30, 2019
Study Completion (Actual)
December 30, 2020
Study Registration Dates
First Submitted
October 25, 2018
First Submitted That Met QC Criteria
November 6, 2018
First Posted (Actual)
November 7, 2018
Study Record Updates
Last Update Posted (Actual)
October 13, 2021
Last Update Submitted That Met QC Criteria
October 5, 2021
Last Verified
October 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Neurobehavioral Manifestations
- Genetic Diseases, Inborn
- Genetic Diseases, X-Linked
- Carbohydrate Metabolism, Inborn Errors
- Metabolism, Inborn Errors
- Mental Retardation, X-Linked
- Intellectual Disability
- Heredodegenerative Disorders, Nervous System
- Brain Diseases, Metabolic
- Mitochondrial Diseases
- Brain Diseases, Metabolic, Inborn
- Pyruvate Metabolism, Inborn Errors
- Pyruvate Dehydrogenase Complex Deficiency Disease
- Antineoplastic Agents
- 4-phenylbutyric acid
Other Study ID Numbers
- TIGEM2-PDH
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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