Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03734263
Recruitment Status : Recruiting
First Posted : November 7, 2018
Last Update Posted : November 7, 2018
Sponsor:
Information provided by (Responsible Party):
Nicola Brunetti-Pierri, Fondazione Telethon

Tracking Information
First Submitted Date  ICMJE October 25, 2018
First Posted Date  ICMJE November 7, 2018
Last Update Posted Date November 7, 2018
Actual Study Start Date  ICMJE October 1, 2018
Estimated Primary Completion Date October 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 6, 2018)
  • 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)
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: November 6, 2018)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Use of Phenylbutyrate Therapy for Patients With Pyruvate Dehydrogenase Complex Deficiency.
Official Title  ICMJE Pilot Clinical Trial to Investigate the Safety and Efficacy of Phenylbutyrate Therapy for Patients With Pyruvate Dehydrogenase Complex Deficiency.
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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pyruvate Dehydrogenase Complex Deficiency
Intervention  ICMJE Drug: sodium phenylbutyrate
Enrolled subjects will receive a four-week period of treatment with sodium phenylbutyrate (oral use)
Study Arms  ICMJE Experimental: open label
sodium phenylbutyrate
Intervention: Drug: sodium phenylbutyrate
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 6, 2018)
10
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 1, 2019
Estimated Primary Completion Date October 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Months to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Nicola Brunetti-Pierri, MD +390817463288 brunetti@tigem.it
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03734263
Other Study ID Numbers  ICMJE TIGEM2-PDH
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Nicola Brunetti-Pierri, Fondazione Telethon
Study Sponsor  ICMJE Fondazione Telethon
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Fondazione Telethon
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP