Increasing Ureagenesis in Inborn Errors of Metabolism With N-Carbamylglutamate

• Status: Withdrawn
• Trial end date: 2012-08-01
• Target enrollment: 0
• Participant gender: All

Summary

Hyperammonemia, which can cause brain damage, occurs in many different kinds of inborn errors of metabolism. The investigators propose to determine if short-term (3 day) treatment with N-carbamylglutamate can diminish hyperammonemia by enhancing ureagenesis in these patients. The investigators propose here a short-term (3 day) trial. If it succeeds, the investigators would consider more extensive long-term studies of the drug.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Children's Hospital of Philadelphia
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Criteria

Inclusion Criteria:

• Age range: males or females, ages 3 years - 70 years

• Condition(s): N-acetylglutamate synthetase deficiency, propionic acidemia, methylmalonic acidemia, carbamylphosphate synthase deficiency, ornithine transcarbamylase deficiency and the syndrome of hyperammonemia, hypoglycemia and hyperinsulinemia.

• In addition, healthy volunteers will be studied (ages 18 years - 50 years).

Exclusion Criteria:

• Acutely ill on day of study (fever, evidence of hyperammonemia - ataxia, worsening obtundation, focal neurologic signs, seizures, increased intracranial pressure, vomiting, signs of acute respiratory or enteric illness, headache, confusion, disorientation, acute personality change).

• Girls 11 years of age must have a negative urine/serum pregnancy test within 1 week prior to testing unless having a menstrual period during week of test

• Lactating females

• Hyperammonemia probably refractory to N-carbamylglutamate: other urea cycle disorders (UCD), lysinuric protein intolerance, mitochondrial disorders, congenital lactic acidemia, fatty acid oxidation defects or primary liver disease.

• Amount of blood necessary for study exceeds safe limits.

• Any investigational drug use within 30 days prior to enrollment.

• Parents/guardians or subjects who, in the opinion of the PI, may be non-compliant with study schedules or procedures.

• Subjects who do not meet all the enrollment criteria may not be enrolled. Any violations of these criteria will be reported in accordance with Institutional Review Board (IRB) Policies and Procedures.