Study of Treatment and Metabolism in Patients With Urea Cycle Disorders

Amino Acid Metabolism, Inborn Errors Clinical Trial

Official title:

Therapeutic and Metabolic Studies of Urea Cycle Disorders: Part A: Nitrogen Flux and Ureagenesis; Part B (Closed): Phase I Adenovirus Vector-Mediated Gene Therapy for Ornithine Transcarbamylase Deficiency

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00004307
• Other study ID #: NCRR-M01RR00188-0606
• Secondary ID: BCM-H4379
• Status: Recruiting
• Phase: Phase 1
• First received: October 18, 1999
• Last updated: June 23, 2005
• Start date: December 1999

Study information

• Verified date: December 2003
• Source: National Center for Research Resources (NCRR)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: The urea cycle is the process in which nitrogen is removed from the blood and converted into urea, a waste product found in urine . Urea cycle disorders are inherited disorders caused by the lack of an enzyme that removes ammonia from the bloodstream. Gene therapy is treatment given to change a gene so that it functions normally. Studying the treatment and metabolism of patients with urea cycle disorders may be helpful in developing new treatments for these disorders.

PURPOSE: Two-part clinical trial to study the treatment and metabolism of patients who have urea cycle disorders.

Description:

PROTOCOL OUTLINE: This protocol involves 2 clinical studies. Part A is a metabolic study of glutamine conversion to urea at different levels of protein intake, while on and off medications. Part B is a dose escalation study of a first-generation adenoviral vector with an E1 deletion and an E3 deletion substitution (d1309) expressing ornithine transcarbamylase (OTC).

In Part A, diet is controlled for protein and calories. Intravenous glutamine and urea are administered. Controls are given intravenous arginine, phenylacetate, and benzoate.

In Part B, groups of 3 patients are given a single low, intermediate, or high dose of intravenous OTC vector. Allopurinol is administered every 12 hours for 12 days. As of 12/10/1999, Part B of the study is closed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 66
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 6 Months to 64 Years

Eligibility

PROTOCOL ENTRY CRITERIA:

Part A. Patients at least 6 months old with ornithine transcarbamylase deficiency (OTC), i.e.: Hemizygous OTC or homozygous autosomal recessive disorder with evidence of complete enzyme deficiency Hemizygous OTC male with late presentation and presumed evidence for residual enzyme activity OTC heterozygotes (molecular diagnosis) with severely symptomatic to asymptomatic disease Obligate heterozygotes for autosomal recessive disorder (parent or genotyped sibling) Normal adult volunteers and genotyped siblings entered as controls Part B. Metabolically stable heterozygous OTC females aged 18 to under 65 Orotic acid level at least 5 times normal on allopurinol Symptoms ranging from severe to asymptomatic acceptable No prior hospitalization for hyperammonemia Exclusion criteria (Parts A and B): Acute or chronic intercurrent illness Pregnancy Acute hyperammonemia

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amino Acid Metabolism, Inborn Errors
• Metabolism, Inborn Errors
• Urea Cycle Disorders, Inborn

Intervention

Behavioral:
• Protein and calorie controlled diet

Genetic:
• Ornithine transcarbamylase vector

Locations

Country	Name	City	State
United States	Baylor College of Medicine	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
National Center for Research Resources (NCRR)	Baylor College of Medicine

Country where clinical trial is conducted

United States,