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

Urea Cycle Disorders, Inborn Clinical Trial

— BPA/Benzoate  

Official title:

Comparative Efficacy of Phenylbutyrate vs. Benzoate in Urea Cycle Disorders

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02111200
• Other study ID #: H-33157
• Status: Completed
• Phase: N/A
• First received: April 8, 2014
• Last updated: December 9, 2017
• Start date: September 2014
• Est. completion date: October 2015

Study information

• Verified date: October 2017
• Source: Baylor College of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

Inclusion Criteria:

• Healthy volunteers

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.

Related Conditions & MeSH terms

• Disease
• Urea Cycle Disorders, Inborn

Intervention

Drug:
• Sodium Benzoate
Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
• Sodium Phenylbutyrate
Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.

Locations

Country	Name	City	State
United States	Children's Nutrition Research Center/Baylor College of Medicine	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Baylor College of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Urinary Hippuric Acid	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.	4 days per arm
Primary	Urinary PAGN Excretion	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.	4 days per arm
Primary	Total Nitrogen as a Conjugate of the Drug	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.	4 days per arm