Urea Cycle Disorders, InbornBPA/BenzoateNCT02111200

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

A study testing Sodium Benzoate and Sodium Phenylbutyrate in people with Urea Cycle Disorders, Inborn, run by Baylor College of Medicine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 64 yearsHealthy volunteers can take part
Conditions the study is for: Urea Cycle Disorders, Inborn
What is being tested?: Sodium Benzoate and Sodium Phenylbutyrate
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 7 participants
Where: 1 siteUnited States
Study dates: Sep 2014to Oct 2015
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 64 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Healthy volunteers

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Children's Nutrition Research Center/Baylor College of Medicine
Houston, Texas, 77030

Other trials in United States

About this study

Official title: Comparative Efficacy of Phenylbutyrate vs. Benzoate in Urea Cycle Disorders

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
Being tested: Sodium Benzoate, Sodium Phenylbutyrate
Keywords: urea cycle disorders
Medical subject headings: Urea Cycle Disorders, Inborn

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Sodium BenzoateDrug
Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.
Sodium PhenylbutyrateDrug
Also called Buphenyl (tm)
Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.

Study groups in NCT02111200
Study group	Role	What they receive
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 Receives: 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 Receives: 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 Receives: Drug: Sodium Benzoate; Drug: Sodium Phenylbutyrate

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 4 days per arm

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2014Oct 2015

First posted11 Apr 2014 (estimated)
Study startSep 2014
Primary completionOct 2015
Study completionOct 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Urea Cycle Disorders, InbornStudies of the same condition, open and under way.
More trials run by Baylor College of MedicineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 7 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02111200
Sponsor's protocol ID: H-33157
Acronym: BPA/Benzoate
Status last verified: Oct 2017
First submitted: 8 Apr 2014
Last updated: 9 Jan 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 9 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Comparative Efficacy of Phenylbutyrate vs. Benzoate in Urea Cycle Disorders
ClinicalTrials.gov ID: NCT02111200
Acronym / sponsor ID: BPA/Benzoate / H-33157
Conditions: Urea Cycle Disorders, Inborn
Keywords: urea cycle disorders
Study type: Interventional
Recruitment status: Completed
Enrolment: 7 participants (actual)
Lead sponsor: Baylor College of MedicineUniversity, hospital or other
Study start: Sep 2014
Primary completion: Oct 2015 (actual)
Study completion: Oct 2015 (actual)
First posted: 11 Apr 2014 (estimated)
Results: Posted 8 Dec 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

We expect to find that phenylbutyrate is more effective at removing nitrogen than benzoate or a combination of the two.

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Sodium Benzoate arm	Active comparator	Drug: Sodium BenzoateSodium benzoate 5.5 g/m2/day divided into three equal doses per day (maximum dose 12 g/day) for 3 days
Sodium Phenylbutyrate arm	Active comparator	Drug: Sodium PhenylbutyrateSodium phenylbutyrate 7.15 g/m2/day divided into three equal doses per day (maximum dose of 20 g/day) for 3 days
Mix Arm	Active comparator	Drug: Sodium Benzoate, Drug: Sodium PhenylbutyrateSodium 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

Who may qualify

Ages: 18 to 64 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (1 listed)

Healthy volunteers

Key exclusion criteria (1 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Sodium BenzoateSubjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.	Drug	Mix Arm, Sodium Benzoate arm
Sodium PhenylbutyrateAlso: Buphenyl (tm)Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) for 3 days.	Drug	Mix Arm, Sodium Phenylbutyrate arm

Primary outcome

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.

Results and safety

Results posted to the registry on 8 Dec 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sodium Phenylbutyrate->MIX->Sodium Benzoate (4 Days)	3	3
Sodium Benzoate->MIX-> Sodium Phenylbutyrate (4 Days)	2	2
MIX->Sodium Benzoate-> Sodium Phenylbutyrate (4 Days)	1	1
MIX-> Sodium Phenylbutyrate-> Sodium Benzoate (4 Days)	1	1

Primary outcome: Urinary Hippuric Acid

Time frame: 4 days per arm. Mean (Standard Deviation). Unit: mmol/24 hours

Measure	Sodium Benzoate Arm n = 7	Sodium Phenylbutyrate Arm n = 7	Mix Arm n = 7
Value	16.4 (3.1)	0 (0)	10.5 (1.7)

Primary outcome: Urinary PAGN Excretion

Time frame: 4 days per arm. Mean (Standard Deviation). Unit: mmol/24 hours

Measure	Sodium Benzoate Arm n = 7	Sodium Phenylbutyrate Arm n = 7	Mix Arm n = 7
Value	0 (0)	15.3 (2.3)	9.3 (0.8)

Primary outcome: Total Nitrogen as a Conjugate of the Drug

Time frame: 4 days per arm. Mean (Standard Deviation). Unit: mmol/24 hours

Measure	Sodium Benzoate Arm n = 7	Sodium Phenylbutyrate Arm n = 7	Mix Arm n = 7
Value	16.4 (3.1)	29 (3.3)	30.7 (4.5)

Adverse events

Time frame: The adverse events were collected through 4 days of each study arm.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Sodium Benzoate Treatment	0 of 7 (0%)	3 of 7 (42.9%)	0 of 7
Sodium Phenylbutyrate Treatment	0 of 7 (0%)	5 of 7 (71.4%)	0 of 7
MIX Treatment	0 of 7 (0%)	3 of 7 (42.9%)	0 of 7

Limitations and caveats (from the sponsor): A limitation of this study is that it was conducted in healthy subjects in whom ammonemia is well-controlled. Ammonia control was not assessed.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Juan C Marini, DVM., PhD principal investigator

Baylor College of Medicine

Sandesh CS Nagamani, MD, FACMG principal investigator

Baylor College of Medicine

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Sodium Benzoate and Sodium Phenylbutyrate in people with Urea Cycle Disorders, Inborn, run by Baylor College of Medicine at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Urinary Hippuric Acid (time frame: 4 days per arm). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02111200.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2018.