Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency:

NCT02616484 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: IRB201500698 - A - N
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 10

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. Funding Source - FDA OOPD

Conditions

Pyruvate Dehydrogenase Complex Deficiency

Keywords

Sodium Dichloroacetate; Treatment of PDCD with Dichloroacetate

Outcome Measures

Primary Outcomes (2)

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

  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).

  9 months

• The number of participants with adverse events will be compared between the groups.

  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.

  9 months

Secondary Outcomes (3)

• Karnofsky/Lansky Performance Status

  9 months

• Blood lactate levels between the groups.

  9 months

• Plasma β-hydroxybutyrate (β-OHB) concentrations between the groups.

  9 months

Other Outcomes (5)

• The number of participants with adverse events based on the age at randomization between the groups.

  9 months

• The number of participants with adverse events based on dietary fat intake between the groups.

  9 months

• The efficacy will be measured using the Observer Reported Outcome (ObsRO) scale of health based on the genetic-based dosing between the groups.

  9 months

Study Arms (2)

Dichloroacetate, then Placebo

ACTIVE COMPARATOR

This group will start on the Dichloroacetate (DCA) treatment which will last for 4 months. After 4 months a 1 month washout period will occur. After the 1 month the group will crossover to the placebo treatment for 4 months. 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

Drug: Dichloroacetate (DCA); Other: Placebo; Genetic: Genotype

Placebo, then Dichloroacetate

PLACEBO COMPARATOR

This group will start on the placebo treatment which will last for 4 months. After 4 months a 1 month washout period will occur. After the 1 month the group will crossover to the Dichloroacetate (DCA) treatment for 4 months. 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

Drug: Dichloroacetate (DCA); Other: Placebo; Genetic: Genotype

Interventions

Dichloroacetate (DCA) DRUG

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.

Also known as: Sodium Dichloroacetate

Dichloroacetate, then Placebo; Placebo, then Dichloroacetate

Placebo OTHER

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.

Dichloroacetate, then Placebo; Placebo, then Dichloroacetate

Genotype GENETIC

Participants will be genotyped to determine GSTZ1 haplotype status.

Dichloroacetate, then Placebo; Placebo, then Dichloroacetate

Eligibility Criteria

• Age: 6 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 6 m through 17 y
• Presence of characteristic clinical or metabolic features of pyruvate dehydrogenase complex deficiency (PDCD) and
• Presence of a known pathogenic mutation of a gene that is specifically associated with PDCD.

Sponsors & Collaborators

• Saol Therapeutics Inc: lead
• Medosome Biotec LLC: collaborator

Study Sites (10)

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida

Gainesville, Florida, 32611, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 15224, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84113, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Related Publications (36)

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  BACKGROUND

MeSH Terms

Conditions

Pyruvate Dehydrogenase Complex Deficiency Disease

Interventions

Dichloroacetic Acid; Genotype

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Metabolism, Inborn Errors; Pyruvate Metabolism, Inborn Errors; Carbohydrate Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Mitochondrial Diseases

Intervention Hierarchy (Ancestors)

Chloroacetates; Acetates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydrocarbons, Chlorinated; Hydrocarbons, Halogenated; Hydrocarbons; Genetic Phenomena

Study Officials

• Richard Neibeger, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2015
• First Posted: November 30, 2015
• Study Start: July 14, 2020
• Primary Completion: August 27, 2025
• Study Completion: August 27, 2025
• Last Updated: May 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)