Advertisement

Topics

Prevention of Dichloroacetate Toxicity

2014-07-23 21:55:09 | BioPortfolio

Summary

This is a study to determine the safety of dichloroacetate (DCA) with a low-tyrosine diet given with or without nitisinone (NTBC) in children with chronic lactic acidosis (CLA).

Description

DCA is being studied for the treatment of patients with CLA, which is a rare collection of mitochondrial metabolism errors causing cellular energy failure and early death. DCA causes reversible liver and peripheral nerve toxicity and it interrupts both tyrosine and heme metabolism. The inhibitory effect of DCA on mammalian tyrosine metabolism elicits biochemical changes similar to those observed in hereditary tyrosinemia type I (HT). However, some reports and studies indicate substantial reduction in the biochemical and clinical consequences of HT may occur when patients are treated concomitantly with a low-tyrosine diet (LTD) and the chemical NTBC, which inhibits an early step in tyrosine catabolism. Possibly, the same dietary and pharmacologic interventions may mitigate or prevent toxicity associated with chronic DCA exposure.

Patients visit the Center 5 times over a 1-year period, usually for 2 to 3 days per visit, for an extensive series of clinical and biochemical tests. Visit 1 is for baseline examinations and blood and urine chemistries and to educate the patient on an LTD. This visit lasts approximately 7 days to determine acceptable circulating tyrosine concentrations for LTD formula at discharge. Patients are provided with tubes to take to local laboratories every 2 weeks for blood work. Patients are readmitted in 1 month to determine adherence to diet and serum tyrosine levels. Patients who evidence dietary compliance, no adverse effects, and a willingness to continue are placed in 1 of 2 treatment arms: DCA plus an LTD plus placebo or DCA plus an LTD plus NTBC. Thereafter, patients return during Months 5, 9, and 13, which completes their 1-year treatment phase.

Study Design

Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Safety/Efficacy Study, Masking: Double-Blind, Primary Purpose: Prevention

Conditions

Acidosis, Lactic

Intervention

Nitisinone (NTBC), Dichloroacetate, Low-tyrosin diet

Location

University of Florida
Gainesville
Florida
United States
32610

Status

Recruiting

Source

FDA Office of Orphan Products Development

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-07-23T21:55:09-0400

Clinical Trials [858 Associated Clinical Trials listed on BioPortfolio]

Dichloroacetate Kinetics, Metabolism and Toxicology

Dichloroacetate (DCA) is a product of water chlorination and a metabolite of certain industrial solvents, thus making it a chemical of environmental concern. However, DCA is also used as a...

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 a...

Study On the Role of Mitochondrial Dysfunction in the Pathogenesis of Metformin-associated Lactic Acidosis

Metformin is the first line drug of choice for the treatment of type II diabetes. Lactic acidosis can develop as a side effect, especially when renal failure leads to drug accumulation. La...

Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency:

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 pyruvat...

Study of NTBC for Tyrosinemia I

OBJECTIVES: I. Assess the safety and efficacy of NTBC in children with tyrosinemia I. II. Evaluate the effects of NTBC on survival, rate of neurologic crises, improvement in renal tubula...

PubMed Articles [2891 Associated PubMed Articles listed on BioPortfolio]

Metformin-Induced Lactic Acidosis: A Case Study.

Metformin is the first line management for patients with Type 2 diabetes mellitus. Metformin-induced lactic acidosis (MALA) is a severe side effect of metformin in high doses. However, there have no...

Comparative analysis of lactic acidosis induced by linezolid and vancomycin therapy using cohort and case-control studies of incidence and associated risk factors.

Lactic acidosis is a rare complication of linezolid (LZD) therapy, and its incidence and risk factors remain unknown. This study aimed to compare the incidence of LZD-associated lactic acidosis (LALA)...

Severe lactic acidosis requiring continuos haemodiafiltration in a young patient with unrecognized metabolic abnormality. Case report.

Lactic acidosis (LA) is the most common form of metabolic acidosis, defined by lactate values greater than 5 mmol/L and pH

Combined metformin-associated lactic acidosis and euglycemic ketoacidosis.

In renal failure metformin can lead to lactic acidosis. Additional inhibition of hepatic gluconeogenesis by accumulation of the drug may aggravate fasting-induced ketoacidosis. We report the occurrenc...

Metformin-associated lactic acidosis. Report of one case.

Metformin-associated lactic acidosis is a severe and infrequent adverse event. Early diagnosis is essential to start an early treatment, which often has favorable results. We report a 56 years old non...

Medical and Biotech [MESH] Definitions

Acidosis caused by accumulation of lactic acid more rapidly than it can be metabolized. It may occur spontaneously or in association with diseases such as diabetes mellitus, leukemia, or liver failure.

Increase in blood LACTATE concentration often associated with SEPTIC SHOCK; LUNG INJURY; SEPSIS; and DRUG TOXICITY. When hyperlactatemia is associated with low body pH (acidosis) it is LACTIC ACIDOSIS.

An inherited metabolic disorder caused by deficient enzyme activity in the PYRUVATE DEHYDROGENASE COMPLEX, resulting in deficiency of acetyl CoA and reduced synthesis of acetylcholine. Two clinical forms are recognized: neonatal and juvenile. The neonatal form is a relatively common cause of lactic acidosis in the first weeks of life and may also feature an erythematous rash. The juvenile form presents with lactic acidosis, alopecia, intermittent ATAXIA; SEIZURES; and an erythematous rash. (From J Inherit Metab Dis 1996;19(4):452-62) Autosomal recessive and X-linked forms are caused by mutations in the genes for the three different enzyme components of this multisubunit pyruvate dehydrogenase complex. One of the mutations at Xp22.2-p22.1 in the gene for the E1 alpha component of the complex leads to LEIGH DISEASE.

Sepsis associated with HYPOTENSION or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to LACTIC ACIDOSIS; OLIGURIA; or acute alteration in mental status.

A biguanide hypoglycemic agent with actions and uses similar to those of METFORMIN. Although it is generally considered to be associated with an unacceptably high incidence of lactic acidosis, often fatal, it is still available in some countries. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290)

More From BioPortfolio on "Prevention of Dichloroacetate Toxicity"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Pediatrics
Pediatrics is the general medicine of childhood. Because of the developmental processes (psychological and physical) of childhood, the involvement of parents, and the social management of conditions at home and at school, pediatrics is a specialty. With ...

Hepatology
Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...


Searches Linking to this Trial