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Difficulty with recruitment and agreed with Sponsor to report completed data as case reports
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The purpose of this study is to see how tetrahydrobiopterin therapy (BH4; also known as sapropterin dihydrochloride or Kuvan) affects measures of oxidative stress and endothelial function in patients with Phenylketonuria (PKU).
Oxidative stress will be induced by having participants eat a meal in polyunsaturated fats. The investigators will see how participants respond to the meal challenge over the course of 6 hours.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BH4 Non-Responders | Experimental | Participants in this group have PKU and were deemed unresponsive to the drug. They will attend their first study visit, and proceed through the meal challenge without BH4. They will then take BH4 for 2 weeks. The second meal challenge will be performed with the participant's final dose of BH4. |
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| Healthy Controls | Experimental | Participants in this group match an enrolled PKU participant in terms of age, gender, and body mass index class. They will participate in a single study visit and will not be given BH4. |
|
| BH4 Responders | Experimental | Participants in this group will use their already prescribed BH4 with the meal challenge and be assessed at a single study visit. They will take their prescribed BH4 with the meal. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Kuvan | Drug | Participants in the BH4 Non-Responder group will be given a 20 mg/kg body weight/day dose of Kuvan to take on a daily basis for two weeks. The last dose will be administered at the participant's study visit 2. |
| Measure | Description | Time Frame |
|---|---|---|
| Lipid Peroxidation | Markers will be assessed every other hour for each 6-hour study visit. Kuvan responders and healthy controls will only be assessed at one 6-hour study visit. Kuvan non-responders will be assessed at two study visits (a baseline visit, and a visit after two weeks of Kuvan therapy). Values will be assessed groupwise and also assessed for intrapersonal change in the Kuvan non-responsive group. Time frame of participation is estimated at one month. | Lipid peroxidation will be measured every other hour for six hours at baseline (study visit 1) for all study groups |
| C-Reactive Protein (CRP) | Markers will be assessed every other hour for each 6-hour study visit. Kuvan responders and healthy controls will only be assessed at one 6-hour study visit. Kuvan non-responders will be assessed at two study visits (a baseline visit, and a visit after two weeks of Kuvan therapy). Values will be assessed groupwise and also assessed for intrapersonal change in the Kuvan non-responsive group. Time frame of participation is estimated at one month. | CRP will be measured every other hour for six hours at baseline (study visit 1) for all study groups and again during a second visit 2 weeks after baseline in BH4 Non-Responders only (study visit 2) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rani H Singh, PhD | Emory University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory University | Decatur | Georgia | 30033 | United States |
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| Label | URL |
|---|---|
| Study Website | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | BH4 Non-Responders | Participants in this group have PKU and were deemed unresponsive to the drug. They will attend their first study visit, and proceed through the meal challenge without BH4. They will then take BH4 for 2 weeks. The second meal challenge will be performed with the participant's final dose of BH4. Kuvan: Participants in the BH4 Non-Responder group will be given a 20 mg/kg body weight/day dose of Kuvan to take on a daily basis for two weeks. The last dose will be administered at the participant's study visit 2. Meal Challenge: At each study visit, patients will receive a meal high in polyunsaturated fats that will promote a transitory increase in oxidative stress measures and endothelial dysfunction |
| FG001 | Healthy Controls | Participants in this group match an enrolled PKU participant in terms of age, gender, and body mass index class. They will participate in a single study visit and will not be given BH4. Meal Challenge: At each study visit, patients will receive a meal high in polyunsaturated fats that will promote a transitory increase in oxidative stress measures and endothelial dysfunction |
| FG002 | BH4 Responders | Participants in this group will use their already prescribed BH4 with the meal challenge and be assessed at a single study visit. They will take their prescribed BH4 with the meal. Meal Challenge: At each study visit, patients will receive a meal high in polyunsaturated fats that will promote a transitory increase in oxidative stress measures and endothelial dysfunction |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline Study Visit |
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| Study Visit 2 (Non-responders Only) |
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| ID | Title | Description |
|---|---|---|
| BG000 | BH4 Non-Responders | Participants in this group have PKU and were deemed unresponsive to the drug. They will attend their first study visit, and proceed through the meal challenge without BH4. They will then take BH4 for 2 weeks. The second meal challenge will be performed with the participant's final dose of BH4. Kuvan: Participants in the BH4 Non-Responder group will be given a 20 mg/kg body weight/day dose of Kuvan to take on a daily basis for two weeks. The last dose will be administered at the participant's study visit 2. Meal Challenge: At each study visit, patients will receive a meal high in polyunsaturated fats that will promote a transitory increase in oxidative stress measures and endothelial dysfunction |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Lipid Peroxidation | Markers will be assessed every other hour for each 6-hour study visit. Kuvan responders and healthy controls will only be assessed at one 6-hour study visit. Kuvan non-responders will be assessed at two study visits (a baseline visit, and a visit after two weeks of Kuvan therapy). Values will be assessed groupwise and also assessed for intrapersonal change in the Kuvan non-responsive group. Time frame of participation is estimated at one month. | Study was terminated due to difficulty recruiting patients, thus analysis was limited to preliminary data on 11 patients only. TBARS was measured in 3 BH4 responders only - data were unavailable for 8 other participants (2 responders, 3 non-responders, and 3 controls) due to inadequate sample volume. | Posted | Mean | Standard Deviation | umole/L | Lipid peroxidation will be measured every other hour for six hours at baseline (study visit 1) for all study groups |
|
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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 | BH4 Non-Responders | Participants in this group have PKU and were deemed unresponsive to the drug. They will attend their first study visit, and proceed through the meal challenge without BH4. They will then take BH4 for 2 weeks. The second meal challenge will be performed with the participant's final dose of BH4. Kuvan: Participants in the BH4 Non-Responder group will be given a 20 mg/kg body weight/day dose of Kuvan to take on a daily basis for two weeks. The last dose will be administered at the participant's study visit 2. Meal Challenge: At each study visit, patients will receive a meal high in polyunsaturated fats that will promote a transitory increase in oxidative stress measures and endothelial dysfunction |
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Early termination leading to small number of subjects analyzed.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kathryn Coakley | Emory University | 404-778-1286 | kcoakle@emory.edu |
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| ID | Term |
|---|---|
| D010661 | Phenylketonurias |
| 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 |
|---|---|
| C003402 | sapropterin |
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|
| Meal Challenge | Other | At each study visit, patients will receive a meal high in polyunsaturated fats that will promote a transitory increase in oxidative stress measures and endothelial dysfunction |
|
| NOT COMPLETED |
|
| BG001 | Healthy Controls | Participants in this group match an enrolled PKU participant in terms of age, gender, and body mass index class. They will participate in a single study visit and will not be given BH4. Meal Challenge: At each study visit, patients will receive a meal high in polyunsaturated fats that will promote a transitory increase in oxidative stress measures and endothelial dysfunction |
| BG002 | BH4 Responders | Participants in this group will use their already prescribed BH4 with the meal challenge and be assessed at a single study visit. They will take their prescribed BH4 with the meal. Meal Challenge: At each study visit, patients will receive a meal high in polyunsaturated fats that will promote a transitory increase in oxidative stress measures and endothelial dysfunction |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Age, Categorical | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| high-sensitivity CRP | Mean | Standard Deviation | mg/L |
|
Participants in this group have PKU and were deemed unresponsive to the drug. They will attend their first study visit, and proceed through the meal challenge without BH4. They will then take BH4 for 2 weeks. The second meal challenge will be performed with the participant's final dose of BH4. Kuvan: Participants in the BH4 Non-Responder group will be given a 20 mg/kg body weight/day dose of Kuvan to take on a daily basis for two weeks. The last dose will be administered at the participant's study visit 2. Meal Challenge: At each study visit, patients will receive a meal high in polyunsaturated fats that will promote a transitory increase in oxidative stress measures and endothelial dysfunction |
| OG001 | Healthy Controls | Participants in this group match an enrolled PKU participant in terms of age, gender, and body mass index class. They will participate in a single study visit and will not be given BH4. Meal Challenge: At each study visit, patients will receive a meal high in polyunsaturated fats that will promote a transitory increase in oxidative stress measures and endothelial dysfunction |
| OG002 | BH4 Responders | Participants in this group will use their already prescribed BH4 with the meal challenge and be assessed at a single study visit. They will take their prescribed BH4 with the meal. Meal Challenge: At each study visit, patients will receive a meal high in polyunsaturated fats that will promote a transitory increase in oxidative stress measures and endothelial dysfunction |
|
|
| Primary | C-Reactive Protein (CRP) | Markers will be assessed every other hour for each 6-hour study visit. Kuvan responders and healthy controls will only be assessed at one 6-hour study visit. Kuvan non-responders will be assessed at two study visits (a baseline visit, and a visit after two weeks of Kuvan therapy). Values will be assessed groupwise and also assessed for intrapersonal change in the Kuvan non-responsive group. Time frame of participation is estimated at one month. | Study was terminated due to difficulty recruiting patients, thus analysis was limited to preliminary data on 11 patients only. CRP was measured in 10 subjects - data were unavailable for 1 control participant due to inadequate sample volume. | Posted | Mean | Standard Deviation | mg/dl | CRP will be measured every other hour for six hours at baseline (study visit 1) for all study groups and again during a second visit 2 weeks after baseline in BH4 Non-Responders only (study visit 2) |
|
|
|
| 0 |
| 4 |
| 0 |
| 4 |
| EG001 | Healthy Controls | Participants in this group match an enrolled PKU participant in terms of age, gender, and body mass index class. They will participate in a single study visit and will not be given BH4. Meal Challenge: At each study visit, patients will receive a meal high in polyunsaturated fats that will promote a transitory increase in oxidative stress measures and endothelial dysfunction | 0 | 3 | 0 | 3 |
| EG002 | BH4 Responders | Participants in this group will use their already prescribed BH4 with the meal challenge and be assessed at a single study visit. They will take their prescribed BH4 with the meal. Meal Challenge: At each study visit, patients will receive a meal high in polyunsaturated fats that will promote a transitory increase in oxidative stress measures and endothelial dysfunction | 0 | 5 | 0 | 5 |
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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 |
|
| 4-hours post meal (n=3, 2, 5) |
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| 6-hours post meal (n=3, 2, 5) |
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| Baseline V2, prior to meal challenge (n=3, 0, 0) |
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| 2-hours post meal (V2; n=3, 0, 0) |
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| 4-hours post meal (V2; n=3, 0, 0) |
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| 6-hours post meal (V2; n=3, 0, 0) |
|