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

Primary Purpose

Urea Cycle Disorders, Inborn

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Sodium Benzoate
Sodium Phenylbutyrate
Sponsored by
Baylor College of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Urea Cycle Disorders, Inborn focused on measuring urea cycle disorders

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Children's Nutrition Research Center/Baylor College of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Sodium Benzoate arm

Sodium Phenylbutyrate arm

Mix Arm

Arm Description

Sodium benzoate 5.5 g/m2/day divided into three equal doses per day (maximum dose 12 g/day) for 3 days

Sodium phenylbutyrate 7.15 g/m2/day divided into three equal doses per day (maximum dose of 20 g/day) for 3 days

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

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

Full Information

First Posted
April 8, 2014
Last Updated
December 9, 2017
Sponsor
Baylor College of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT02111200
Brief Title
Comparative Efficacy of Phenylbutyrate (PBA) vs. Benzoate in Urea Cycle Disorders
Acronym
BPA/Benzoate
Official Title
Comparative Efficacy of Phenylbutyrate vs. Benzoate in Urea Cycle Disorders
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
September 2014 (undefined)
Primary Completion Date
October 2015 (Actual)
Study Completion Date
October 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Baylor College of Medicine

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urea Cycle Disorders, Inborn
Keywords
urea cycle disorders

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sodium Benzoate arm
Arm Type
Active Comparator
Arm Description
Sodium benzoate 5.5 g/m2/day divided into three equal doses per day (maximum dose 12 g/day) for 3 days
Arm Title
Sodium Phenylbutyrate arm
Arm Type
Active Comparator
Arm Description
Sodium phenylbutyrate 7.15 g/m2/day divided into three equal doses per day (maximum dose of 20 g/day) for 3 days
Arm Title
Mix Arm
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Sodium Benzoate
Intervention Description
Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
Intervention Type
Drug
Intervention Name(s)
Sodium Phenylbutyrate
Other Intervention Name(s)
Buphenyl (tm)
Intervention Description
Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
Primary Outcome Measure Information:
Title
Urinary Hippuric Acid
Description
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.
Time Frame
4 days per arm
Title
Urinary PAGN Excretion
Description
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.
Time Frame
4 days per arm
Title
Total Nitrogen as a Conjugate of the Drug
Description
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.
Time Frame
4 days per arm

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Juan C Marini, DVM., PhD
Organizational Affiliation
Baylor College of Medicine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Sandesh CS Nagamani, MD, FACMG
Organizational Affiliation
Baylor College of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Nutrition Research Center/Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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