N-Carbamylglutamate (Carbaglu) In The Treatment Of Hyperammonemia

NCT00843921 | Unknown Phase 2 DMC

• 2 other identifiers: CNMC 36941R01HD058567-01
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Inborn Errors of Metabolism

Keywords

Hyperammonemia

Outcome Measures

Primary Outcomes (1)

• Rate of ureagenesis as determined by 13C enrichment of urea

  3 days of treatment

Secondary Outcomes (5)

• Plasma ammonia concentration

  3 days

• Plasma amino acid levels

  3 days

• Urine Orotic Acid

  3 days

• Blood Urea Nitrogen (BUN)

  3 days

• Routine safety laboratory tests (CBC, LFTs, Creatinine)

  3 days

Study Arms (1)

Carbaglu

EXPERIMENTAL

Investigate whether a 3-day treatment with NCG can improve or restore urea genesis capacity in patients with NAGS, CPSI, or OTC deficiency or PA or MMA using surrogate markers: \[13C\] label incorporation into urea and plasma levels of ammonia, urea nitrogen (BUN) and amino acids

Drug: N-carbamylglutamate

Interventions

N-carbamylglutamate DRUG

100 mg/kg/day or 2.2 g/M2/day in 3-4 divided doses for 3 days

Also known as: Carglumic acid, Carbaglu

Carbaglu

Eligibility Criteria

• Age: 1 Day - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Between 1 day - 70 years of age
• 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.
• 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:
• Recurrent hyperammonemic episodes (NH3 \>70umol/l) with elevated plasma glutamine (\>/= 800umol/l)
• Urinary orotate levels within normal limits (\</= 5 umol/mmol urine creatinine)
• Absence of argininosuccinic acid in blood or urine
• Low or normal level of citrulline (\</=92umol/l) and arginine (\</= 179 umol/l) and ornithine (\</=159umol/l) within normal limits in blood
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Mendel Tuchman: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Childrens Research Institute

Washington D.C., District of Columbia, 20010, United States

Location

MeSH Terms

Conditions

Metabolism, Inborn Errors; Hyperammonemia

Interventions

N-carbamylglutamate; carglumic acid

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Mendel Tuchman, MD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: February 12, 2009
• First Posted: February 13, 2009
• Study Start: August 1, 2008
• Primary Completion: April 25, 2018
• Study Completion: June 30, 2020
• Last Updated: February 17, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will share

Locations

US (1)