Increasing Ureagenesis in Inborn Errors of Metabolism With N-Carbamylglutamate

Children's Hospital of Philadelphia (CHOP)

Status and phase

Withdrawn

Phase 2

Conditions

Carbamyl Phosphate Synthetase Deficiency

Inborn Errors of Metabolism

Urea Cycle Disorders, Inborn

Methylmalonic Acidemia

Propionic Acidemia

Treatments

Drug: N-carbamylglutamate

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT01341379

R01HD058567 (U.S. NIH Grant/Contract)

10-007806

Details and patient eligibility

About

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.

Full description

To determine whether brief (3 day) treatment with N-carbamylglutamate can improve ureagenesis in adult healthy controls and patients with the following inborn errors of metabolism: N-acetylglutamate synthetase deficiency, propionic acidemia, methylmalonic acidemia, carbamylphosphate synthase deficiency, ornithine transcarbamylase deficiency and the syndrome of hyperammonemia, hypoglycemia and hyperinsulinemia (HHH Syndrome).
To determine if such treatment improves other indicators of abnormal nitrogen metabolism such as elevated blood levels of glutamine, glycine and alanine.

Sex

All

Ages

3 to 70 years old

Volunteers

Accepts Healthy Volunteers

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.