Phase II Study of Sodium Phenylbutyrate, Sodium Benzoate, Sodium Phenylacetate, and Dietary Intervention for Urea Cycle Disorders

OBJECTIVES:

I. Assess the safety and efficacy of sodium phenylbutyrate, sodium benzoate, sodium phenylacetate, and dietary intervention in patients with urea cycle disorders.

Study Overview

• Status: Completed
• Conditions: Amino Acid Metabolism, Inborn Errors
• Intervention / Treatment: Drug: Sodium Benzoate; Drug: Sodium Phenylacetate; Drug: Sodium Phenylbutyrate; Behavioral: Dietary Intervention

Detailed Description

PROTOCOL OUTLINE: This protocol describes several clinical studies of pharmacologic and dietary management in patients with urea cycle disorders.

Patients with carbamyl phosphate synthetase and ornithine transcarbamylase deficiency are treated with a low-protein diet, essential amino acids (for neonatal onset disease), caloric supplementation, oral sodium phenylbutyrate (now approved as a prescription drug 11/97), and citrulline or arginine free base.

Patients with argininosuccinic acid synthetase deficiency are treated with a low-protein diet, caloric supplementation, oral sodium phenylbutyrate (now approved as a prescription drug 11/97), and arginine free base.

Patients with argininosuccinic aciduria (AA) are treated with a low-protein diet, caloric supplementation, and arginine free base. (Discontinued 11/97) Any patient who develops hyperammonemia is treated with intravenous sodium benzoate, sodium phenylbutyrate, and arginine hydrochloride; benzoate and phenylbutyrate are not given to patients with AA.

If ammonium stabilizes at normal or near normal levels, intravenous medications are gradually replaced by oral medications. If there is no significant decrease in ammonium within 8 hours, patients begin hemodialysis.

Concurrent therapy with ondansetron, high caloric intake, and mannitol for elevated intracranial pressure is allowed. Dietary and intravenous nitrogen is prohibited. (Discontinued 11/97)

• Study Type: Interventional
• Enrollment: 20
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

PROTOCOL ENTRY CRITERIA:

Urea cycle deficiency, i.e.: Carbamyl phosphate synthetase deficiency (CPSD) Ornithine transcarbamylase deficiency (OTCD) Argininosuccinic acid synthetase deficiency (ASD) Argininosuccinic aciduria (AA)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: National Center for Research Resources (NCRR)
• Collaborators: Johns Hopkins University
• Investigators: Study Chair: Saul W. Brusilow, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start: January 1, 1985

Study Registration Dates

• First Submitted: February 24, 2000
• First Submitted That Met QC Criteria: February 24, 2000
• First Posted (Estimate): February 25, 2000

Study Record Updates

• Last Update Posted (Estimate): June 24, 2005
• Last Update Submitted That Met QC Criteria: June 23, 2005
• Last Verified: December 1, 2001

More Information

Terms related to this study

• Keywords: rare disease; inborn errors of metabolism; urea cycle disorder
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Amino Acid Metabolism, Inborn Errors; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antifungal Agents; 4-phenylbutyric acid; Phenylacetic acid; Sodium Benzoate
• Other Study ID Numbers: 199/11753; JHUSM-11753