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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02111200
First Posted: April 11, 2014
Last Update Posted: December 8, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Juan Marini, Baylor College of Medicine
  Purpose

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.


Condition Intervention
Urea Cycle Disorders, Inborn Drug: Sodium Benzoate Drug: Sodium Phenylbutyrate

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Comparative Efficacy of Phenylbutyrate vs. Benzoate in Urea Cycle Disorders

Resource links provided by NLM:


Further study details as provided by Juan Marini, Baylor College of Medicine:

Primary Outcome Measures:
  • Urinary Hippuric Acid [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.


Enrollment: 7
Study Start Date: September 2014
Study Completion Date: October 2015
Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Sodium Benzoate arm
Sodium benzoate 5.5 g/m2/day divided into three equal doses per day (maximum dose 12 g/day) for 3 days
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.
Active Comparator: Sodium Phenylbutyrate arm
Sodium phenylbutyrate 7.15 g/m2/day divided into three equal doses per day (maximum dose of 20 g/day) for 3 days
Drug: 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.
Other Name: Buphenyl (tm)
Active Comparator: Mix Arm
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
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.
Drug: 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.
Other Name: Buphenyl (tm)

  Eligibility

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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02111200


Locations
United States, Texas
Children's Nutrition Research Center/Baylor College of Medicine
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Investigators
Principal Investigator: Juan C Marini, DVM., PhD Baylor College of Medicine
Principal Investigator: Sandesh CS Nagamani, MD, FACMG Baylor College of Medicine
  More Information

Responsible Party: Juan Marini, Principal Investigator, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT02111200     History of Changes
Other Study ID Numbers: H-33157
First Submitted: April 8, 2014
First Posted: April 11, 2014
Results First Submitted: September 1, 2017
Results First Posted: December 8, 2017
Last Update Posted: December 8, 2017
Last Verified: October 2017

Keywords provided by Juan Marini, Baylor College of Medicine:
urea cycle disorders

Additional relevant MeSH terms:
Brain Diseases, Metabolic, Inborn
Disease
Urea Cycle Disorders, Inborn
Pathologic Processes
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
4-phenylbutyric acid
Sodium Benzoate
Antineoplastic Agents
Antifungal Agents
Anti-Infective Agents