PhenylketonuriaBH4&PKUNCT00688844
Nutritional and Neurotransmitter Changes in PKU Subjects on BH4
An observational study of Phenylketonuria, run by Emory University at 2 sites in United States.
Trial summary
HYPOTHESIS: The investigators hypothesize that KuvanTM therapy could influence nutritional and body composition parameters and neurotransmitter concentrations in pediatric and adult PKU subjects. Read more about this study
- Who is it for?
- Ages 4 years and olderHealthy volunteers can take part
- Conditions the study is for
- Phenylketonuria
- What is being tested?
- KuvanTM Therapy
- How many people
- 58 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2008to Oct 2010
- Phase
- Observational
- 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 4 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Phenylketonuria (PKU) subjects ages 4 through adulthood who plan to start BH4 therapy but are not currently on BH4.
Who may be able to join
- Diagnosed with PKU
- ability to provide informed consent (or have legal guardian who can provide informed consent)
- at least 4 years of age
- planning on trying BH4 treatment
Who cannot join
- Pregnant
- unable to provide informed consent
- less than 4 years of age
- currently taking BH4
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Emory Hospital, CIN/ACTSI
Atlanta, Georgia, 30322
Emory University Genetics Clinic
Decatur, Georgia, 30033
About this study
Official title: Baseline Evaluation and Long-term Follow-up of Nutritional Status and Neurotransmitter Concentrations in Phenylketonuria Patients Initiating Treatment With Sapropterin Dihydrochloride (KuvanTM), a Tetrahydrobiopterin Analog.
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.
Read the detailed description
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:
- To record nutritional biomarkers, body composition, bone density, and measures of nutrient intake in a phenylketonuria subject group at baseline and for one year after start of KuvanTM therapy.
- To investigate changes in monoamine neurotransmitter synthesis in a phenylketonuria subject group at baseline and for one year after start of KuvanTM therapy.
- Evaluate changes in quality of life (QOL) for PKU subjects beginning KuvanTM therapy
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.
- Conditions
- Phenylketonuria
- Being tested
- KuvanTM Therapy
- Keywords
- PKU, Phenylketonuria, BH4, Kuvan, Tetrahydrobiopterin, Sapropterin Dihydrochloride, Nutrition, PHE, Phenylalanine, PAH, Phenylalanine hydroxylase, Neurotransmitters, Serotonin, Catecholamines, Diet, Body Fat, Bone Density
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KuvanTM TherapyDrug
Also called BH4, Kuvan
BH4 treatment was prescribed by each participant's medical provider, not an intervention that was assigned as part of the current study.
| Study group | Role | What they receive |
|---|---|---|
| PKU subjects - baseline | Male and female subjects with PKU at baseline starting KuvanTM therapy. Receives: Drug: KuvanTM Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in BMI at 12 Months
Change in Body mass index (BMI) from baseline of Kuvan study to 12 months post-baseline
Measured: 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
Measured: 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)
Measured: 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)
Measured: Baseline and 12 months
Change From Baseline in Plasma Phenylalanine at 12 Months
Full amino acid panel, including phenylalanine, analyzed in fasting plasma samples.
Measured: 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
Measured: 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
Measured: Baseline and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2008 (estimated)
- Study startOct 2008
- Primary completionOct 2010
- Study completionOct 2010
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PhenylketonuriaStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- BioMarin Pharmaceutical, Atlanta Clinical and Translational Science Institute
- Responsible party
- Principal investigator, Rani Singh, Emory University
- Investigators
- Rani H Singh, PhD, RD, Principal investigator, Emory University Department of Human Genetics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00688844
- Sponsor's protocol ID
- IRB00007828
- Acronym
- BH4&PKU
- Status last verified
- May 2015
- First submitted
- 29 May 2008
- Last updated
- 8 Jun 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 28465125
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Baseline Evaluation and Long-term Follow-up of Nutritional Status and Neurotransmitter Concentrations in Phenylketonuria Patients Initiating Treatment With Sapropterin Dihydrochloride (KuvanTM), a Tetrahydrobiopterin Analog.
- ClinicalTrials.gov ID
- NCT00688844
- Acronym / sponsor ID
- BH4&PKU / IRB00007828
- Conditions
- Phenylketonuria
- Keywords
- PKU, Phenylketonuria, BH4, Kuvan, Tetrahydrobiopterin, Sapropterin Dihydrochloride, Nutrition, PHE
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- BioMarin Pharmaceutical, Atlanta Clinical and Translational Science Institute
- Study start
- Oct 2008
- Primary completion
- Oct 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 3 Jun 2008 (estimated)
- Results
- Posted 20 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- To record nutritional biomarkers, body composition, bone density, and measures of nutrient intake in a phenylketonuria subject group at baseline and for one year after start of KuvanTM therapy.
- To investigate changes in monoamine neurotransmitter synthesis in a phenylketonuria subject group at baseline and for one year after start of KuvanTM therapy.
- Evaluate changes in quality of life (QOL) for PKU subjects beginning KuvanTM therapy
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PKU subjects - baseline | – | Drug: KuvanTM TherapyMale and female subjects with PKU at baseline starting KuvanTM therapy. |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Phenylketonuria (PKU) subjects ages 4 through adulthood who plan to start BH4 therapy but are not currently on BH4.
Key inclusion criteria (4 listed)
- Diagnosed with PKU
- ability to provide informed consent (or have legal guardian who can provide informed consent)
- at least 4 years of age
- planning on trying BH4 treatment
Key exclusion criteria (4 listed)
- Pregnant
- unable to provide informed consent
- less than 4 years of age
- currently taking BH4
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 |
|---|---|---|
| KuvanTM TherapyAlso: BH4, KuvanBH4 treatment was prescribed by each participant's medical provider, not an intervention that was assigned as part of the current study. | Drug | PKU subjects - baseline |
Primary outcome
Change From Baseline in BMI at 12 Months
Time frame: Baseline and 12 months
Change in Body mass index (BMI) from baseline of Kuvan study to 12 months post-baseline
Change From Baseline in Bone Mineral Density (BMD) at 12 Months
Time frame: Baseline and 12 months
Change in bone mineral density (BMD) from baseline of Kuvan study to 12 months post-baseline
Change From Baseline in Percent (%) Lean Mass at 12 Months
Time frame: Baseline and 12 months
% lean mass was measured via dual energy x-ray absorptiometry (DXA)
Change From Baseline in Percent (%) Fat Mass at 12 Months
Time frame: Baseline and 12 months
Percent fat mass measured via dual energy x-ray absorptiometry (DXA)
Change From Baseline in Plasma Phenylalanine at 12 Months
Time frame: Baseline and 12 months
Full amino acid panel, including phenylalanine, analyzed in fasting plasma samples.
Change From Baseline in Total Dietary Protein Intake at 12 Months
Time frame: Baseline and 12 months
Total dietary protein intake assessed through 3-day food records - calculated as average protein intake (grams/day) in the 3 days recorded
Change From Baseline in Phenylalanine Intake at 12 Months
Time frame: Baseline and 12 months
Total dietary phenylalanine assessed through 3-day food records - calculated as average phenylalanine intake (grams/day) in the 3 days recorded
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28465125Jani 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.
- BH4 \& PKU Study OpportunityLink provided by the sponsor.
Related trials for Phenylketonuria
RecruitingPhase 1
A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-181 in Subjects With Phenylketonuria
Phenylketonuria
RecruitingPhase 2
A Study of MZE782 in Adults With PKU
Phenylketonuria (PKU)
RecruitingPhase 3
A Study of Sepiapterin in Participants With Phenylketonuria (PKU)
Phenylketonuria
Recruiting
Impact of Phenylalanine Elevations on Brain and Cognition in Adult PKU Carriers
Carrier of Phenylketonuria, Healthy
RecruitingPhase 3
A Study of JNT-517 in Participants With Phenylketonuria (PKU)
Phenylketonuria
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.
Rani H Singh, PhD, RD principal investigator
Emory University Department of Human Genetics
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Phenylketonuria, run by Emory University at 2 sites 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 4 inclusion and 4 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 8 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 20 Aug 2014). 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?
Change From Baseline in BMI at 12 Months (time frame: Baseline and 12 months). The study lists 7 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 NCT00688844, which also lists 1 linked publication.
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 8 Jun 2015.