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

NCT02111200 | Completed Results

• 1 other identifier: H-33157
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Urea Cycle Disorders, Inborn

Keywords

urea cycle disorders

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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

Study Arms (3)

Sodium Benzoate arm

ACTIVE COMPARATOR

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

Sodium Phenylbutyrate arm

ACTIVE COMPARATOR

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

Mix Arm

ACTIVE COMPARATOR

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; Drug: Sodium Phenylbutyrate

Interventions

Sodium Benzoate DRUG

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

Mix Arm; Sodium Benzoate arm

Sodium Phenylbutyrate DRUG

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

Also known as: Buphenyl (tm)

Mix Arm; Sodium Phenylbutyrate arm

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy volunteers

You may not qualify if:

• 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.

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (1)

Children's Nutrition Research Center/Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Urea Cycle Disorders, Inborn

Interventions

Sodium Benzoate; 4-phenylbutyric acid

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Benzoic Acid; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Limitations and Caveats

A limitation of this study is that it was conducted in healthy subjects in whom ammonemia is well-controlled. Ammonia control was not assessed.

Results Point of Contact

• Title: Mahshid Azamian
• Organization: Baylor

azamian@bcm.edu

832-822-1529

Study Officials

• Juan C Marini, DVM., PhD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• Sandesh CS Nagamani, MD, FACMG

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 8, 2014
• First Posted: April 11, 2014
• Study Start: September 1, 2014
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: January 9, 2018
• Results First Posted: December 8, 2017

Record last verified: 2017-10

Locations

US (1)