Document Detail


Evaluation of long-term treatment of children with congenital lactic acidosis with dichloroacetate.
MedLine Citation:
PMID:  18411236     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: The purpose of this research was to report results on long-term administration of dichloroacetate in 36 children with congenital lactic acidosis who participated previously in a controlled trial of this drug. PATIENTS AND METHODS: We conducted a randomized control trial, followed by an open-label study. Data were analyzed for each patient from the time they began treatment through May 2005. RESULTS: Subject exposure to dichloroacetate totaled 110.42 years. Median height and weight increased over time, but the standardized values declined slightly and remained below the first percentile. There were no significant changes in biochemical metabolic indices, except for a 2% rise in total protein and a 22% increase in 24-hour urinary oxalate. Both the basal and carbohydrate meal-induced rises in lactate were blunted by dichloroacetate. The median cerebrospinal fluid lactate also decreased over time. Conduction velocity decreased and distal latency increased in peroneal nerves. Mean 3-year survival for all of the subjects was 79%. CONCLUSIONS: Oral dichloroacetate is generally well tolerated in young children with congenital lactic acidosis. Although continued dichloroacetate exposure is associated with evidence of peripheral neuropathy, it cannot be determined whether this is attributable mainly to the drug or to progression of underlying disease.
Authors:
Peter W Stacpoole; Lesa R Gilbert; Richard E Neiberger; Paul R Carney; Edward Valenstein; Douglas W Theriaque; Jonathan J Shuster
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2008-04-14
Journal Detail:
Title:  Pediatrics     Volume:  121     ISSN:  1098-4275     ISO Abbreviation:  Pediatrics     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-05-02     Completed Date:  2008-06-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376422     Medline TA:  Pediatrics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e1223-8     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, General Clinical Research Center, JHMHC, Gainesville, FL 32610-0226, USA. peter.stacpoole@medicine.ufl.edu
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MeSH Terms
Descriptor/Qualifier:
Acidosis, Lactic / complications,  congenital*,  drug therapy*,  metabolism
Administration, Oral
Adolescent
Adult
Child
Child, Preschool
Dichloroacetate / administration & dosage*,  adverse effects
Double-Blind Method
Female
Humans
Infant
Kaplan-Meiers Estimate
Lactic Acid / blood
Male
Mitochondrial Encephalomyopathies / complications
Neural Conduction
Pyruvate Dehydrogenase Complex Deficiency Disease / complications
Grant Support
ID/Acronym/Agency:
FD-R-001500/FD/FDA HHS; M01 RR00082/RR/NCRR NIH HHS; P42 ES 07375/ES/NIEHS NIH HHS; R01 ES07355/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
13425-80-4/Dichloroacetate; 50-21-5/Lactic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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