Clinical trial
Phase 3 Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency:
Name
IRB201500698 - A - N
Description
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
Trial arms
Trial start
2020-07-14
Estimated PCD
2025-03-30
Trial end
2025-03-30
Status
Active (not recruiting)
Phase
Early phase I
Treatment
Dichloroacetate (DCA)
Study medication DCA is a liquid formulation 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 12-14 mg/kg/12hr DCA. EGT non-carriers will receive 6-7 mg/kg/12 hr.
Arms:
Dichloroacetate, then Placebo, Placebo, then Dichloroacetate
Other names:
Sodium Dichloroacetate
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.
Arms:
Dichloroacetate, then Placebo, Placebo, then Dichloroacetate
Genotype
Participants will be genotyped to determine GSTZ1 haplotype status.
Arms:
Dichloroacetate, then Placebo, Placebo, then Dichloroacetate
Size
34
Primary endpoint
The efficacy will be measured between the groups by using the Observer Reported Outcome (ObsRO) measure of health.
9 months
The number of participants with adverse events will be compared between the groups.
9 months
Eligibility criteria
Inclusion Criteria:
* 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.
Exclusion Criteria:
A genetic mitochondrial disease other than those stipulated under inclusion criteria Primary disorders of amino acid metabolism; primary disorders of fatty acid oxidation Secondary lactic acidosis due to impaired oxygenation or circulation (cardiomyopathy or congenital heart defect) Renal insufficiency (defined as: requires chronic dialysis or serum creatinine ≥ 1.2 mg/dl; creatinine clearance \<60 ml/min Primary hepatic disease unrelated to PDCD Pregnancy or breast feeding
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'CROSSOVER', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 34, 'type': 'ACTUAL'}}
Updated at
2023-06-29
1 organization
2 products
1 indication
Organization
University of FloridaProduct
DichloroacetateProduct
Genotype