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| Name | Class |
|---|---|
| BioMarin Pharmaceutical | INDUSTRY |
| Atlanta Clinical and Translational Science Institute | OTHER |
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HYPOTHESIS: The investigators hypothesize that KuvanTM therapy could influence nutritional and body composition parameters and neurotransmitter concentrations in pediatric and adult PKU subjects.
SUMMARY: Though the investigators know that KuvanTM lowers blood Phe levels and improves tolerance for natural protein in at least half of the PKU (Phenylketonuria) patient population, investigators do not know the full effects this medicine will have on the patient's diet, or what impact the medicine or diet changes will have on the body composition or nutrient status of PKU patients. Since KuvanTM may also help the body produce neurotransmitters, investigators also want to find out if taking KuvanTM changes neurotransmitter levels in PKU patients, and if PKU patients who are benefitting from KuvanTM feel less stigmatized and have a better outlook on life as a result of the treatment.
Therefore, the research study has several objectives. These are to investigate the impact KuvanTM therapy has on (1) body composition parameters of PKU patients: such as lean body mass, percent body fat, bone density, weight gain, and growth (2) dietary changes, and the effect of those changes, on intake of calories and essential nutrients (3) changes in blood biomarkers of certain nutrients (4) blood and urine neurotransmitter levels, since these changes could indicate improved neurological functioning, (5) and quality of life of PKU patients, who may feel less burdened due to the dietary freedom KuvanTM provides.
BACKGROUND : Tetrahydrobiopterin (BH4) is a treatment option newly available to phenylketonuria (PKU) patients within the United States as the pharmaceutical KuvanTM. This small molecule functions as a cofactor in multiple enzyme systems, including the metabolism of phenylalanine into tyrosine by the enzyme phenylalanine hydroxylase (PAH).
HYPOTHESIS: The investigators hypothesize that KuvanTM therapy could influence nutritional and body composition parameters and neurotransmitter concentrations in pediatric and adult PKU subjects.
OBJECTIVES:
METHODOLOGY: Investigators intend to enroll 60 PKU patients, ages 4 to adulthood, who are planning to begin BH4 treatment as prescribed by their medical provider. Patients will be given 4 weeks to demonstrate a response to KuvanTM as determined by a drop in plasma PHE by ≥15%. All patients, regardless of response to KuvanTM, will be allowed to continue in the study. All subjects will be followed for a full 12 months while monitoring nutrient intake, nutritional biomarkers, serotonin and catecholamine levels, and QOL. Two-tailed statistical analysis with α=0.05 will be used to compare results between responders and nonresponders, as well as compare follow-up values with baseline measures.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PKU subjects - baseline | Male and female subjects with PKU at baseline starting KuvanTM therapy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| KuvanTM Therapy | Drug | BH4 treatment was prescribed by each participant's medical provider, not an intervention that was assigned as part of the current study. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in BMI at 12 Months | Change in Body mass index (BMI) from baseline of Kuvan study to 12 months post-baseline | Baseline and 12 months |
| Change From Baseline in Bone Mineral Density (BMD) at 12 Months | Change in bone mineral density (BMD) from baseline of Kuvan study to 12 months post-baseline | Baseline and 12 months |
| Change From Baseline in Percent (%) Lean Mass at 12 Months | % lean mass was measured via dual energy x-ray absorptiometry (DXA) | Baseline and 12 months |
| Change From Baseline in Percent (%) Fat Mass at 12 Months | Percent fat mass measured via dual energy x-ray absorptiometry (DXA) | Baseline and 12 months |
| Change From Baseline in Plasma Phenylalanine at 12 Months | Full amino acid panel, including phenylalanine, analyzed in fasting plasma samples. | Baseline and 12 months |
| Change From Baseline in Total Dietary Protein Intake at 12 Months | Total dietary protein intake assessed through 3-day food records - calculated as average protein intake (grams/day) in the 3 days recorded | Baseline and 12 months |
| Change From Baseline in Phenylalanine Intake at 12 Months | Total dietary phenylalanine assessed through 3-day food records - calculated as average phenylalanine intake (grams/day) in the 3 days recorded |
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| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Serotonin at 12 Months | Objective: 1 year prospective cohort of PKU patients introduced to sapropterin (Kuvan)to evaluate peripheral neurotransmitter changes across time. | Baseline and 12 months |
Inclusion Criteria:
Exclusion Criteria:
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Phenylketonuria (PKU) subjects ages 4 through adulthood who plan to start BH4 therapy but are not currently on BH4.
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| Name | Affiliation | Role |
|---|---|---|
| Rani H Singh, PhD, RD | Emory University Department of Human Genetics | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory Hospital, CIN/ACTSI | Atlanta | Georgia | 30322 | United States | ||
| Emory University Genetics Clinic |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28465125 | Derived | Jani R, Coakley K, Douglas T, Singh R. Protein intake and physical activity are associated with body composition in individuals with phenylalanine hydroxylase deficiency. Mol Genet Metab. 2017 Jun;121(2):104-110. doi: 10.1016/j.ymgme.2017.04.012. Epub 2017 Apr 28. |
| Label | URL |
|---|---|
| BH4 \& PKU Study Opportunity | View source |
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There were no exclusions of subjects once enrolled.
Recruitment lasted 1 year from October 2008 - October 2009. Recruitment occurred at the Emory University Genetics Clinic, Department of Human Genetics in Decatur, GA.
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| ID | Title | Description |
|---|---|---|
| FG000 | Subjects With Phenylketonuria Starting Sapropterin Therapy | Subjects with Phenylketonuria starting sapropterin therapy for the purpose of lowering blood phenylalanine levels. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Subjects With Phenylketonuria Starting Sapropterin Therapy | Subjects with Phenylketonuria starting sapropterin therapy for the purpose of lowering blood phenylalanine levels. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Change From Baseline in BMI at 12 Months | Change in Body mass index (BMI) from baseline of Kuvan study to 12 months post-baseline | Data missing for 2 participants | Posted | Mean | Standard Deviation | kg/m^2 | Baseline and 12 months |
|
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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 | Subjects With Phenylketonuria Starting Sapropterin Therapy | Subjects with Phenylketonuria starting sapropterin therapy for the purpose of lowering blood phenylalanine levels. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sinus and general respiratory infections | Infections and infestations | Non-systematic Assessment | Patients were asked to keep record of illnesses and other adverse events between visits. Patients were encouraged to call in adverse events that occurred between visits but were also queried at each study visit. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Rani H. Singh | Emory University | 404-448-8519 | rsingh@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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Blood plasma Blood platelets Whole blood Urine
|
| Baseline and 12 months |
| Decatur |
| Georgia |
| 30033 |
| United States |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Primary | Change From Baseline in Bone Mineral Density (BMD) at 12 Months | Change in bone mineral density (BMD) from baseline of Kuvan study to 12 months post-baseline | Data missing for 3 participants | Posted | Mean | Standard Deviation | grams/centimeter^2 | Baseline and 12 months |
|
|
|
|
| Primary | Change From Baseline in Percent (%) Lean Mass at 12 Months | % lean mass was measured via dual energy x-ray absorptiometry (DXA) | Data missing for 3 participants | Posted | Mean | Standard Deviation | Percent Lean Mass | Baseline and 12 months |
|
|
|
|
| Primary | Change From Baseline in Percent (%) Fat Mass at 12 Months | Percent fat mass measured via dual energy x-ray absorptiometry (DXA) | Data missing for 3 participants | Posted | Mean | Standard Deviation | Percent Fat Mass | Baseline and 12 months |
|
|
|
|
| Primary | Change From Baseline in Plasma Phenylalanine at 12 Months | Full amino acid panel, including phenylalanine, analyzed in fasting plasma samples. | Posted | Mean | Standard Deviation | Micromoles per liter | Baseline and 12 months |
|
|
|
|
| Primary | Change From Baseline in Total Dietary Protein Intake at 12 Months | Total dietary protein intake assessed through 3-day food records - calculated as average protein intake (grams/day) in the 3 days recorded | Dietary intake not submitted by 11 participants at 12 months. | Posted | Mean | Standard Deviation | grams per day | Baseline and 12 months |
|
|
|
|
| Primary | Change From Baseline in Phenylalanine Intake at 12 Months | Total dietary phenylalanine assessed through 3-day food records - calculated as average phenylalanine intake (grams/day) in the 3 days recorded | Dietary intake not submitted by 11 participants at 12 months. | Posted | Mean | Standard Deviation | grams per day | Baseline and 12 months |
|
|
|
|
| Other Pre-specified | Change From Baseline in Serotonin at 12 Months | Objective: 1 year prospective cohort of PKU patients introduced to sapropterin (Kuvan)to evaluate peripheral neurotransmitter changes across time. | Not Posted | Baseline and 12 months |
| 0 |
| 58 |
| 20 |
| 58 |
|
| Headache | Nervous system disorders | Non-systematic Assessment | Headaches or migraines reported by patients |
|
| Gastrointestinal upset (not flu) | Gastrointestinal disorders | Non-systematic Assessment | Diarrhea or acid reflux |
|
| Urinary tract infection | Renal and urinary disorders | Non-systematic Assessment | One UTI case due to congenital kidney deformity which patient had surgically corrected a few weeks later. |
|
| Flu and flu-type sickness | Infections and infestations | Non-systematic Assessment | Confirmed and suspected flu as reported by patients |
|
| Sore throat | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment | Includes sore throat from strep, flu, cold, or general sore throat. |
|
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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 |