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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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 |
|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Juan C Marini, DVM., PhD | Baylor College of Medicine | Principal Investigator |
| Sandesh CS Nagamani, MD, FACMG | Baylor College of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Nutrition Research Center/Baylor College of Medicine | Houston | Texas | 77030 | United States |
There was no washout period prior to enrollment. Individuals who were enrolled in the trial were not on any medications.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sodium Phenylbutyrate->MIX->Sodium Benzoate (4 Days) |
|
| FG001 | Sodium Benzoate->MIX-> Sodium Phenylbutyrate (4 Days) |
|
| FG002 | MIX->Sodium Benzoate-> Sodium Phenylbutyrate (4 Days) |
|
| FG003 | MIX-> Sodium Phenylbutyrate-> Sodium Benzoate (4 Days) |
|
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
This was a cross over design study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Sodium Phenylbutyrate->MIX->Sodium Benzoate |
|
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Deviation | mmol/24 hours | 4 days per arm |
|
The adverse events were collected through 4 days of each study arm.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sodium Benzoate Treatment | Sodium benzoate 5.5 g/m2/day divided into three equal doses per day (maximum dose 12 g/day) for 3 days 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal discomfort | Gastrointestinal disorders | Non-systematic Assessment |
A limitation of this study is that it was conducted in healthy subjects in whom ammonemia is well-controlled. Ammonia control was not assessed.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mahshid Azamian | Baylor | 832-822-1529 | azamian@bcm.edu |
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| ID | Term |
|---|---|
| D056806 | Urea Cycle Disorders, Inborn |
| ID | Term |
|---|---|
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D020160 | Sodium Benzoate |
| C075773 | 4-phenylbutyric acid |
| ID | Term |
|---|---|
| D019817 | Benzoic Acid |
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
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| 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. |
|
|
| BG001 | Sodium Benzoate->MIX-> Sodium Phenylbutyrate |
|
| BG002 | MIX->Sodium Benzoate-> Sodium Phenylbutyrate |
|
| BG003 | MIX-> Sodium Phenylbutyrate-> Sodium Benzoate |
|
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 |
| 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 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. |
| OG002 | 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 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. 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. |
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | mmol/24 hours | 4 days per arm |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | mmol/24 hours | 4 days per arm |
|
|
|
| 0 |
| 7 |
| 0 |
| 7 |
| 3 |
| 7 |
| EG001 | Sodium Phenylbutyrate Treatment | Sodium phenylbutyrate 7.15 g/m2/day divided into three equal doses per day (maximum dose of 20 g/day) for 3 days 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. | 0 | 7 | 0 | 7 | 5 | 7 |
| EG002 | MIX Treatment | 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 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. 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. | 0 | 7 | 0 | 7 | 3 | 7 |
| Lab anormalities | Investigations | Non-systematic Assessment |
|
| Itch | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
|
| Headache | General disorders | Non-systematic Assessment |
|
| Toe injury | General disorders | Non-systematic Assessment | Unrelated to the study procedures |
|
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| D009422 | Nervous System Diseases |
| D000592 | Amino Acid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D009930 |
| Organic Chemicals |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |