Clinical Trial: Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency:

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Phase 3 Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency:

Brief Summary:

The objective of this research study is to conduct a pivotal phase 3 trial of treatment with the investigational drug dichloroacetate (DCA) in young children with deficiency of the pyruvate dehydrogenase complex (PDC). PDC deficiency (PDCD) is the most common cause of congenital lactic acidosis and is a frequently fatal metabolic disease of childhood for which no proven treatment exists. The investigators predict that DCA represents targeted potential therapy for PDCD because of its ability to increase both the catalytic activity and stability of the enzyme complex. The conclusions of numerous laboratory and clinical investigations are consistent with this postulate and have led to the designation of DCA as an Orphan Product for congenital lactic acidosis by the Food and Drug Administration.

A novel Observer reported outcome (ObsRO) survey that is completed by study participant's parent/caregiver, is the efficacy outcome measure.

Detailed Summary:

Clinical sites will be established across the United States for study participation. The investigators will conduct a randomized, placebo-controlled, double-blind trial of 24 children, aged 6 months through 17 years, with confirmed diagnosis of PDC Deficiency.

Study participants complete Screening procedures at Visit 1 to confirm eligibility for study participation. Screening study procedures include medical history review and physical exam; blood and urine collection. Study participants complete Baseline study procedures at Visit 2 prior to randomization to treatment. Baseline study procedures include, medical history review and physical exam; blood and urine collection; 3 day food record; training to complete the ObsRO daily survey. The ObsRO is a survey developed for this study to evaluate how study participants are feeling and functioning in the home setting. The ObsRO survey is completed by the study participant parent/caregiver every day during both treatment periods (study medication and placebo) of study participation (approximately 9 months).

During treatment period 1 and 2 (4 months of study medication and 5 months of placebo), the study participant will communicate with the study team at least 2 times per month to evaluate the child's level of health, and compliance with daily survey completion and taking the study medication. The study medication will be shipped to the study participants home each month.

Study participants will complete Visit 3 during month 5 to complete study assessments at the same clinical site. Visit 3 study procedures include medical history review and physical exam; blood and urine collection; review of the ObsRO survey completion; 3 day food record.

Study participants who complete both tre
Sponsor: University of Florida

Current Primary Outcome:

• The efficacy will be measured between the groups by using the Observer Reported Outcome (ObsRO) measure of health. [ Time Frame: 9 months ]
  The efficacy of dichloroacetate will be determined by applying a novel Observer Reported Outcome (ObsRO) measure of health. The ObsRO scores will be graded on a Likert Scale from 0-4. (0 being absent and 4 being extremely severe).
• The number of participants with adverse events will be compared between the groups. [ Time Frame: 9 months ]
  This is to evaluate the safety and tolerability of dichloroacetate by comparing the 1) number and 2) severity of adverse events during both the double-blind and open label treatment phases.

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Karnofsky/Lansky Performance Status [ Time Frame: 9 months ]

  The Karnofsky/Lansky performance Scale is completed by the study team. It is a measure of the study participants functional ability to carry on activities of daily living.

  The Karnofsky Scale is used for study participants age greater than 16 years. The Lansky Scale is used for study participants age less than 16 years.

• Blood lactate levels between the groups. [ Time Frame: 9 months ]
  The measurement of blood lactate level will be performed.
• Plasma β-hydroxybutyrate (β-OHB) concentrations between the groups. [ Time Frame: 9 months ]
  The measurement of plasma β-hydroxybutyrate (β-OHB) concentrations will be performed.

Original Secondary Outcome:

• Karnofsky/Lansky Performance Status between the groups [ Time Frame: 9 months ]

  The Karnofsky score runs from 100 to 0, where 100 is "perfect" health and 0 is death.

  100 - Normal; no complaints; no evidence of disease. 90 - Able to carry on normal activity; minor signs or symptoms of disease. 80 - Normal activity with effort; some signs or symptoms of disease. 70 - Cares for self; unable to carry on normal activity or to do active work. 60 - Requires occasional assistance, but is able to care for most of their personal needs.

  50 - Requires considerable assistance and frequent medical care. 40 - Disabled; requires special care and assistance. 30 - Severely disabled; hospital admission is indicated although death not imminent.

  20 - Very sick; hospital admission necessary; active supportive treatment necessary.

  10 - Moribund; fatal processes progressing rapidly. 0 - Dead

• Blood lactate levels between the groups. [ Time Frame: 9 months ]
  The measurement of blood lactate level will be performed.
• Plasma β-hydroxybutyrate (β-OHB) concentrations between the groups. [ Time Frame: 9 months ]
  The measurement of plasma β-hydroxybutyrate (β-OHB) concentrations will be performed.

Information By: University of Florida

Dates:
Date Received: November 17, 2015
Date Started: July 29, 2017
Date Completion: June 30, 2020
Last Updated: May 3, 2017
Last Verified: May 2017