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.

Condition	Treatment or Intervention	Phase
Amino Acid Metabolism, Inborn Errors	Behavior: Protein and calorie controlled diet  Gene Transfer: Ornithine transcarbamylase vector	Phase I

Further Study Details: 

Expected Total Enrollment:  66

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.

Ages Eligible for Study:  6 Months   -   64 Years,  Genders Eligible for Study:  Both

Accepts Healthy Volunteers

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. 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

Texas
      Baylor College of Medicine, Houston,  Texas,  77030,  United States; Recruiting

Study chairs or principal investigators

Brendan Lee,  Study Chair,  Baylor College of Medicine   

Study ID Numbers:  NCRR-M01RR00188-0606; BCM-H4379
Record last reviewed:  December 2003
Last Updated:  March 25, 2005
Record first received:  October 18, 1999
ClinicalTrials.gov Identifier:  NCT00004307
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08