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

• ClinicalTrials.gov Identifier: NCT02111200
• Recruitment Status: Completed
• First Posted: April 11, 2014
• Results First Posted: December 8, 2017
• Last Update Posted: January 9, 2018
• Sponsor: Baylor College of Medicine
• Information provided by (Responsible Party): Juan Marini, Baylor College of Medicine

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.

Condition or disease	Intervention/treatment	Phase
Urea Cycle Disorders, Inborn	Drug: Sodium Benzoate; Drug: Sodium Phenylbutyrate	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• 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
• Study Start Date: September 2014
• Actual Primary Completion Date: October 2015
• Actual Study Completion Date: October 2015

Arms and Interventions

Arm	Intervention/treatment
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)

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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.
3. 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.

Eligibility Criteria

• 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

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
• Other Study ID Numbers: H-33157
• First Posted: April 11, 2014
• Results First Posted: December 8, 2017
• Last Update Posted: January 9, 2018
• Last Verified: October 2017

Keywords provided by Juan Marini, Baylor College of Medicine:

urea cycle disorders

Additional relevant MeSH terms:

Urea Cycle Disorders, Inborn; Disease; Pathologic Processes; Brain Diseases, Metabolic, Inborn; 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; Sodium Benzoate; 4-phenylbutyric acid; Antineoplastic Agents; Antifungal Agents; Anti-Infective Agents