Phase II Pilot Randomized Study of Sodium Dichloroacetate in Patients With Congenital Lactic Acidemia

OBJECTIVES: I. Determine the pharmacokinetics of sodium dichloroacetate (DCA) in patients with congenital lactic acidemia.

II. Determine the efficacy of DCA in decreasing the frequency and/or severity of acute episodes of acidotic illness, improving linear growth, improving neurological or developmental function, or slowing neurological or developmental deterioration in these patients.

PROTOCOL OUTLINE: This is a randomized, double blind, cross over study. Patients are randomized to start with one of two different doses of sodium dichloroacetate (DCA).

Patients receive one of two doses of oral DCA for 6 months, then switch to the alternate dose for 6 months. This course is repeated once.

Patients are followed for up to 2 years.

Completion date provided represents the completion date of the grant per OOPD records

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Diagnosis of stable, persistent lactic acidemia Venous lactate at least 3 mM under basal conditions defined as: At least 4 hours postprandial No concurrent illness

OR

• Diagnosis of cerebral lactic acidemia with elevated lactic acid in CSF but not in the blood
• No organic acidemias or defective gluconeogenesis

--Patient Characteristics--

• Hematopoietic: Hemoglobin at least 7 mg/dL
• Hepatic: Bilirubin no greater than 3 times upper limit of normal (ULN) AST, ALT, or GGT no greater than 10 times ULN
• Renal: Creatinine no greater than 2 mg/dL
• Cardiovascular: Ejection fraction at least 25%
• Other: No hypoglycemia (blood sugar less than 50 mg/dL at no greater than 12 hours fasting) No severe peripheral neuropathy interfering with normal activities of living