OBJECTIVES:
I. Compare the safety of sodium dichloroacetate (DCA) vs placebo in children with congenital lactic acidosis.
II. Determine the quality of life of these patients.
III. Determine the pharmacokinetics and metabolic fate of DCA over the course of drug administration in these patients.
PROTOCOL OUTLINE: This is a randomized, double blind, crossover study. Patients are stratified according to age (3 months to 2 years vs over 2 to 18 years).
All patients receive at least 12 months of sodium dichloroacetate (DCA) during a 2 year period of double blind, crossover evaluation of DCA and placebo by mouth.
Quality of life is assessed before treatment and periodically during treatment.
Completion date provided represents the completion date of the grant per OOPD records
PROTOCOL ENTRY CRITERIA:
--Disease Characteristics--
Diagnosis of congenital lactic acidosis (CLA) meeting the following criteria: Three basal venous lactates at least 2.5 mM, arterial lactates at least 2.0 mM, or CSF lactates at least 2.5 mM OR any combination of these, obtained over at least 1 month and within 6 months OR Increase in blood lactate at least 1.0 mM over basal following a carbohydrate meal challenge
AND
Enzymatic or molecular genetic proof of a defect of pyruvate dehydrogenase complex, one or more respiratory chain enzymes, or a Krebs cycle enzyme OR Over production of C14-lactate from C14-glucose by cultured skin fibroblasts
AND
Ability to withstand an 8 hour (if 2 years and under) or 12 hour (if over 2 years) fast without developing hypoglycemia (blood glucose less than 50 mg/dL)
No secondary lactic acidosis due to impaired oxygenation or circulation
No hyperlactatemia associated with proven biotinidase deficiency (biotin responsive CLA) or with enzyme deficiencies of gluconeogenesis
No primary, defined organic acidurias other than lactic acidosis, for which effective therapy is available (e.g., propionic aciduria)
No primary disorders of amino acid metabolism or fatty acid oxidation
No malabsorption syndromes associated with D-lactic acidosis
--Prior/Concurrent Therapy--
No chronic dialysis
--Patient Characteristics--
Hepatic: No primary hepatic disease unrelated to CLA
Renal: Creatinine less than 1.2 mg/dL OR Creatinine clearance at least 60 mL/min
Other: No concurrent infection or fever