Comparative Efficacy of Phenylbutyrate (PBA) vs. Benzoate in Urea Cycle Disorders

Not Applicable

Completed

• Conditions: Urea Cycle Disorders, Inborn
• Interventions: Drug: Sodium Benzoate; Drug: Sodium Phenylbutyrate

• Registration Number: NCT02111200
• Lead Sponsor: Baylor College of Medicine

Brief Summary

The investigators will study and compare how effectively sodium phenylbutyrate, sodium benzoate, and a combination of the two, help excrete nitrogen in healthy volunteers. Subject participation will require three, separate, four-day study periods at least one week apart. During one study period (also called a treatment arm), subjects will take sodium phenylbutyrate; during another they will take sodium benzoate; during another they will take a combination of the two medications.

We expect to find that phenylbutyrate is more effective at removing nitrogen than benzoate or a combination of the two.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2014-04-08
• Study First Submitted QC: 2014-04-09
• Study First Posted: 2014-04-11
• Study Start: 2014-09
• Primary Completion: 2015-10
• Study Completion: 2015-10
• Disposition First Submitted: 2017-07-14
• Disposition First Submitted QC: 2017-07-20
• Disposition First Posted: 2017-07-24
• Results First Submitted: 2017-09-01
• Status Verified: 2017-10
• Results First Submitted QC: 2017-10-31
• Results First Posted: 2017-12-08
• Last Update Submitted: 2017-12-09
• Last Update Posted: 2018-01-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 7

Inclusion Criteria

• Healthy volunteers

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Exclusion Criteria

• Subjects with (a) a history of frequent dietary protein intolerance, (b) a history of chronic or acute liver diseases which may result in altered hepatic synthetic capacity (e.g., hepatitis), (c) acute or chronic disease or on medications that in the opinion of the clinical investigators will interfere with the measurements (e.g., drugs which may have hepatotoxicity as potential side effects), (d) a physical disability that will interfere with their ability to either conform to the dietary regimes or undergo the isotopic infusions, (e) pregnancy or recent (<6 months)/current lactation, (f) intercurrent evidence of significant hyperammonemia (more than 100 µmol/L), (g) any clinical abnormality of Grade 3 or greater according to the Common Terminology Criteria for Adverse Events v.4.0 (CTCAE), (h) any condition(s) not covered by the CTCAE, or (i) a severe or life-threatening toxicity at screening, will be excluded from the study. Subjects taking ammonia scavenger medications will not be enrolled.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sodium Benzoate arm	Sodium Benzoate	Sodium benzoate 5.5 g/m2/day divided into three equal doses per day (maximum dose 12 g/day) for 3 days
Sodium Phenylbutyrate arm	Sodium Phenylbutyrate	Sodium phenylbutyrate 7.15 g/m2/day divided into three equal doses per day (maximum dose of 20 g/day) for 3 days
Mix Arm	Sodium Benzoate	Sodium Phenylbutyrate 3.575 g/m2/day and Sodium Benzoate 2.75 g/m2/day will be given in three equal doses per day for 3 days
Mix Arm	Sodium Phenylbutyrate	Sodium Phenylbutyrate 3.575 g/m2/day and Sodium Benzoate 2.75 g/m2/day will be given in three equal doses per day for 3 days

Primary Outcome Measures

Name	Time	Method
Urinary Hippuric Acid	4 days per arm	The objective of this protocol is to directly compare the efficacy of benzoate, phenylbutyrate and a combination of the two, to conjugate nitrogenous compounds in healthy volunteers. The nitrogenous compound of interest in each arm would be based on the medication used. This would be hippuric acid in the benzoate arm, phenylacetylglutamine in the phenylbutyrate arm, and hippuric acid AND phenylacetylglutamine in the MIX arm. The mean hippuric acid levels in the phenylbutyrate arm would thus be 0.
Urinary PAGN Excretion	4 days per arm	The objective of this protocol is to directly compare the efficacy of benzoate, phenylbutyrate and a combination of the two, to conjugate nitrogenous compounds in healthy volunteers. The nitrogenous compound of interest in each arm would be based on the medication used. This would be hippuric acid in the benzoate arm, phenylacetylglutamine in the phenylbutyrate arm, and hippuric acid AND phenylacetylglutamine in the MIX arm. The mean phenylacetylglutamine levels in the benzoate arm would thus be 0.
Total Nitrogen as a Conjugate of the Drug	4 days per arm	The objective of this protocol is to directly compare the efficacy of benzoate, phenylbutyrate and a combination of the two, to conjugate nitrogenous compounds in healthy volunteers. The nitrogenous compound of interest in each arm would be based on the medication used. This would be hippuric acid in the benzoate arm, phenylacetylglutamine in the phenylbutyrate arm, and hippuric acid AND phenylacetylglutamine in the MIX arm.

Trial Locations

Locations (1)

Children's Nutrition Research Center/Baylor College of Medicine; 🇺🇸 Houston, Texas, United States