Study of Treatment and Metabolism in Patients With Urea Cycle Disorders

NCT ID: NCT00004307

Last Updated: 2005-06-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-12-31

Brief 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.

Detailed 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.

Conditions

Amino Acid Metabolism, Inborn Errors

Study Design

• Primary Study Purpose: TREATMENT

Interventions

Protein and calorie controlled diet

Intervention Type: BEHAVIORAL

Ornithine transcarbamylase vector

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

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.

Exclusion Criteria

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

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Baylor College of Medicine

OTHER

Sponsor Role: collaborator

National Center for Research Resources (NCRR)

NIH

Sponsor Role: lead

Principal Investigators

Brendan Lee

Role: STUDY_CHAIR

Baylor College of Medicine

Locations

Baylor College of Medicine

Houston, Texas, United States

Site Status: RECRUITING

Countries

United States

Facility Contacts

Susan Carter

Role: primary

scarter@bcm.tmc.edu

832-822-1630

Other Identifiers

BCM-H4379

Identifier Type: -

Identifier Source: secondary_id

NCRR-M01RR00188-0606

Identifier Type: -

Identifier Source: org_study_id