Phase III Randomized Study of Sodium Dichloroacetate in Children With Congenital Lactic Acidosis

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Conditions
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Lactic Acidosis

Intervention / Treatment
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* Drug: sodium dichloroacetate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: sodium dichloroacetate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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disease-related problem/condition, inborn errors of metabolism, lactic acidosis, quality of life, rare disease