N-Carbamylglutamate (Carbaglu) In The Treatment Of Hyperammonemia

• Status: Active, not recruiting
• Trial end date: 2020-06-30
• Target enrollment: 0
• Participant gender: All

Summary

This study is based on the hypothesis that a new drug N-carbamylglutamate (Carbaglu®) will enhance the ability of the liver to dispose of toxic ammonia which accumulates in several metabolic diseases including urea cycle disorders and organic acid disorders.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mendel Tuchman
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Criteria

Inclusion Criteria:

1. Between 1 day - 70 years of age

2. Viable neonates, neonates with uncertain viability are excluded Diagnosed with one of the following five inborn errors of metabolism: NAGS, CPSI,PA, MMA, or OTC deficiency.

3. Diagnostic requirements:

• NAGS deficiency - Identification of pathogenic mutation and/or decreased (<20% of control) NAGS enzyme activity in liver

• CPSI deficiency - decreased (<20% of control) CPSI enzyme activity in liver deficiency of liver CPSI in the presence of normal or substantial activity of OTC (Tuchman et al 1980) and/or molecular confirmation of deleterious mutations (Summary et al 2003).

• High level of clinical suspicion of NAGS or CPSI deficiency - Failure to meet diagnostic criteria for either NAGS or CPSI deficiency as listed above, but:

1. Recurrent hyperammonemic episodes (NH3 >70umol/l) with elevated plasma glutamine (>/= 800umol/l)

2. Urinary orotate levels within normal limits (creatinine)

3. Absence of argininosuccinic acid in blood or urine

4. Low or normal level of citrulline (umol/l) and ornithine (

• OTC deficiency- Identification of pathogenic mutation and/or-pedigree analysis consistent with familial hyperammonemia segregating in an x-linked semi-dominant pattern and/or -<20% of control OTC activity in liver and/or -elevated urinary orotate (>20%umol/mmol creatinine) after allopurinol challenge test

• PA and MMA- diagnostic urine organic acid analysis and confirmation of absence of responsiveness to biotin and vitamin B12 respectively.

Exclusion Criteria:

• Subjects acutely ill on day of the study

• Pregnant females- documentation of a negative pregnancy test within a week prior to testing is required for females 12 years and older, unless having a menstrual period during that week or other circumstances which preclude pregnancy (e.g. hysterectomy, menopause)

• Subjects with hyperammonemia caused by other urea cycle disorders, lysinuric protein intolerance, mitochondrial disorders, congenital lactic academia, fatty acid oxidation defects and primary liver disease

• Subjects requiring a peripherally inserted central catheter (PICC) for blood draws may need to be moderately sedated and are excluded

• Subjects with hemoglobin < 9 g/dl