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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Baylor College of Medicine
Sponsor:
Information provided by (Responsible Party):
Juan Marini, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT02111200
First received: April 8, 2014
Last updated: September 19, 2014
Last verified: September 2014
  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 Phase
UCDs (The Data May be Helpful in the Treatment of UCDs.)
Drug: Sodium Benzoate
Drug: Sodium Phenylbutyrate
Drug: Phenylbutyrate and Benzoate
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: Comparative Efficacy of Phenylbutyrate vs. Benzoate in Urea Cycle Disorders

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Ammonia, hippuric acid and phenylacetylglutamine levels of urea cycle disorder patients taking benzoate, NaPBA or a combination of the two. [ Time Frame: 4 days per arm ] [ Designated as safety issue: No ]
    The objective of this protocol is to directly compare the efficacy of benzoate, phenylbutyrate and a combination of the two, to conjugate nitrogenous compounds and maintain plasma ammonia within normal levels in healthy volunteers.


Estimated Enrollment: 9
Study Start Date: September 2014
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Sodium Benzoate
Sodium benzoate 5.5 g/m2/day divided into three equal doses per day (maximum dose 12 g/day)
Drug: Sodium Benzoate
Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) until they return on Day 4.
Other Name: benzoate
Active Comparator: Sodium Phenylbutyrate
PBA 7.15 g/m2/day divided into three equal doses per day (maximum dose of 20 g/day)
Drug: Sodium Phenylbutyrate
Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) until they return on Day 4.
Other Name: Buphenyl (tm)
Active Comparator: Phenylbutyrate and Benzoate
A combination of PBA and Benzoate (50% of the dose of each drug as indicated above) will be given in three equal doses per day.
Drug: Phenylbutyrate and Benzoate
Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) until they return on Day 4.
Other Name: Buphenyl(tm)

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02111200

Contacts
Contact: Mary A Mullins, BSN 832-822-4263 mullins@bcm.edu

Locations
United States, Texas
Children's Nutrition Research Center/Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Mary A Miller, BSN    832-822-4263    mullins@bcm.edu   
Principal Investigator: Sandesh C Sreenath Nagamani, MD         
Principal Investigator: Juan C Marini, DVM, PhD         
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

Additional Information:
No publications provided

Responsible Party: Juan Marini, Principal Investigator, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT02111200     History of Changes
Other Study ID Numbers: H-33157
Study First Received: April 8, 2014
Last Updated: September 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:
UCD

Additional relevant MeSH terms:
Brain Diseases, Metabolic, Inborn
Urea Cycle Disorders, 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
4-phenylbutyric acid
Sodium Benzoate
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 30, 2014