Nitisinone and Dichloroacetate and Nitisinone (NTBC) in Chronic Disease and Acidosis, Lactic - Clinical Trials Registry

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

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

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- Florida
  - Gainesville, Florida, United States, 32610
    - University of Florida

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 months to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

Biochemical or molecular genetic proof of a defect in mitochondrial enzyme of glucose metabolism or oxidative phosphorylation.
Clinical history consistent with CLA (e.g., basal hyperlactatemia, stroke-like episodes, neuromuscular degeneration, and seizures).
Ability to withstand an 8-hour fast (if 2 years old or younger) or a 12-hour fast without developing hypoglycemia (blood glucose greater than or equal to 50 mg/dL).

Exclusion criteria:

Secondary lactic acidosis due to impaired oxygenation or circulation.
Hyperlactatemia associated with proven biotinidase deficiency or with enzyme deficiencies of gluconeogenesis.
Primary, defined organic acidurias other than lactic acidosis for which effective therapy is available (e.g., propionic aciduria).
Primary disorders of amino acid metabolism.
Primary disorders of fatty acid oxidation.
Malabsorption syndromes associated with D-lactic acidosis.
Renal insufficiency.
Serum creatinine greater than 1.2 mg/g.
Creatinine clearance less than or equal to 60 mL/min.
Primary hepatic disease unrelated to chronic lactic acidosis.
In patients with pyruvate dehydrogenase enzyme complex deficiency, an inability to maintain a diet greater than 50% calories from fat without biological and/or neurological deterioration.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Masking: Double

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Florida

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2001

Study Completion

September 1, 2005

Study Registration Dates

First Submitted

February 26, 2002

First Submitted That Met QC Criteria