Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency:

Condition(s) studied

Investigational drug(s) / intervention(s)

Dichloroacetate (DCA): Study medication DCA is an oral solution mixed with an artificial sweetener containing aspartame and strawberry extract (50mg/mL) Participants will be genotyped to determine GSTZ1 (glutathione S-transferase Zeta-1) haplotype status, which will stratify this group into 1 of 2 dose regimens: EGT carriers will receive 12 mg/kg/12hr DCA. EGT non-carriers will receive 6 mg/kg/12 hr DCA.

Placebo: Participants will receive the same volume of placebo in liquid form given during DCA treatment arm. Liquid will be an exact replication of DCA formulation with no DCA added.

Genotype: Participants will be genotyped to determine GSTZ1 haplotype status.

Study 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.

Funding Source - FDA OOPD

Eligibility

Primary outcome measure(s)

• The efficacy will be measured between the groups by using the Observer Reported Outcome (ObsRO) measure of health. — 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. — 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.

Trial sites (10)

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