PhenylketonuriaNCT00827762
Behavioral Effects of Kuvan in Children With Mild Phenylketonuria
An observational study of Phenylketonuria, run by Washington University School of Medicine at 4 sites in United States.
Trial summary
The purpose of this study is to determine whether improvements in behavior occur in children with phenylketonuria (PKU) who are taking Kuvan. Read more about this study
- Who is it for?
- Ages 6 to 18 years
- Conditions the study is for
- Phenylketonuria
- What is being tested?
- Kuvan
- How many people
- 2 participants
- Where
- 4 sitesUnited States
- Study dates
- Jan 2009to Jan 2010
- Phase
- Observational
- Are there results?
- None posted in the registry
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 6 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Primary care clinic for phenylketonuria.
Who may be able to join
- Willing and able to provide informed consent and/or assent.
- Willing and able to comply with study procedures.
- Between 6 and 18 years of age, inclusive.
- Intention of physician to prescribe Kuvan.
- Phenylalanine levels between 360μmol/L and 600μmol/L, inclusive, when untreated with dietary restrictions.
- Negative pregnancy test if of childbearing potential.
- Willing to use contraception if sexually active.
Who cannot join
- Treatment with Kuvan within the past 6 months.
- Pregnant, breastfeeding, or planning to become pregnant during study.
- Use of investigational product less than 30 days prior to or during study.
- Concurrent condition that could interfere with participation or safety.
- Any condition creating high risk of poor compliance with study.
- History of major medical disorder unrelated to phenylketonuria.
Show all 9Show fewer
- Perceived to be unreliable or unavailable for study.
- Use of L-Dopa, methotrexate, or other drugs that inhibit folate metabolism.
- Known hypersensitivity to sapropterin or excipients.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Northwestern University/Children's Memorial Hospital
Chicago, Illinois, 60614
University of Missouri
Columbia, Missouri, 65211
Oregon Health & Science University
Portland, Oregon, 97239
Washington University
St Louis, Missouri, 63130
About this study
The purpose of this study is to determine whether improvements in behavior occur in children with phenylketonuria (PKU) who are taking Kuvan.
Read the detailed description
Little research has been conducted to examine behavior and cognition in children with mild PKU/hyperphenylalanemia, but there is evidence of reductions in general intelligence (IQ) (Costello, 1994) and impairments in executive abilities (Diamond, 1994; Gassio, 2005) in this population. It is important to note that the phenylalanine levels of children with mild PKU are approximately equivalent to those of children with classical PKU whose phenylalanine levels have been managed through dietary control. In children with diet-treated PKU, impairments in behavior and cognition are well-documented, particularly in relation to executive abilities (Christ, 2006; White, 2001, 2002). Taken together, these findings suggest that children with mild PKU are at risk for behavioral and cognitive impairments, and it is possible that these impairments may be mitigated by lowering phenylalanine levels through treatment with Kuvan.
To investigate this issue, approximately 20 children with mild PKU from 6 to 18 years of age (inclusive) and their parents will participate in the study. The behavior and cognition of children with mild PKU will be assessed using the following methods: (1) Parents will complete inventories to rate the behavior and cognition of their children; (2) Older children will complete self-report inventories to rate their behavior and cognition; (3) Cognitive tasks assessing IQ and executive aspects of attention (i.e., sustained attention and inhibitory control) will be administered to all children.
The primary objectives are two-fold. First, we will determine if behavior and cognition are compromised in children with mild PKU prior to treatment with Kuvan (baseline). To accomplish this objective, we will administer measures of behavior and cognition that include normative data based on age. We hypothesize that children with mild PKU will have ratings and scores that are ≥ 1 standard deviation from the normative mean. Second, we will determine if behavior and cognition improve in children with mild PKU following treatment with Kuvan. To accomplish this objective, we will administer the same measures of behavior and cognition after 4 and 24 weeks of treatment with Kuvan(4-week and 24-week follow-ups, respectively). We hypothesize that the follow-up ratings and scores of children with mild PKU will improve by ≥ 0.5 standard deviation relative to their baseline ratings and scores.
- Conditions
- Phenylketonuria
- Being tested
- Kuvan
- Keywords
- phenylketonuria, Kuvan, sapropterin, behavior, cognition, executive abilities, attention
- Medical subject headings
- Phenylketonurias, Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KuvanDrug
Also called Sapropterin
20/mg/kg/day taken once daily or as otherwise prescribed by physician as standard care.
| Study group | Role | What they receive |
|---|---|---|
| Phenylketonuria | Individuals with mild phenylketonuria/hyperphenylalanemia who are beginning treatment with Kuvan. Receives: Drug: Kuvan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Behavior Rating Inventory of Executive Function (BRIEF)
Measured: baseline, 4-week follow-up, 24-week follow-up
Secondary outcomes (4)
Behavior Assessment System for Children - Second Edition (BASC-2)
Measured: baseline, 4-week follow-up, 24-week follow-up
Conners 3rd Edition (Conners 3)
Measured: baseline, 4-week follow-up, 24-week follow-up
Conners Continuous Performance Test II Version 5 (CCPT-II Version 5)
Measured: baseline, 4-week follow-up, 24-week follow-up
Matrix Reasoning subtest of the Wechsler Abbreviated Scale of Intelligence (WASI)
Measured: baseline, 4-week follow-up, 24-week follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2009 (estimated)
- Study startJan 2009
- Primary completionJan 2010
- Study completionJan 2010
Why it stopped: Too few participants recruited within timeframe
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for PhenylketonuriaStudies of the same condition, open and under way.
- More trials run by Washington University School 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- BioMarin Pharmaceutical, University of Missouri-Columbia, Northwestern University, Oregon Health and Science University
- Responsible party
- Sponsor
- Investigators
- Desiree White, Ph.D., Principal investigator, Washington University School of MedicineDorothy K. Grange, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00827762
- Sponsor's protocol ID
- MildPKU/Kuvan/White
- Status last verified
- Dec 2013
- First submitted
- 21 Jan 2009
- Last updated
- 5 Dec 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Christ SE, Steiner RD, Grange DK, Abrams RA, White DA. Inhibitory control in children with phenylketonuria. Dev Neuropsychol. 2006;30(3):845-64. doi: 10.1207/s15326942dn3003_5.
PubMed 17083296White DA, Nortz MJ, Mandernach T, Huntington K, Steiner RD. Age-related working memory impairments in children with prefrontal dysfunction associated with phenylketonuria. J Int Neuropsychol Soc. 2002 Jan;8(1):1-11.
PubMed 11843066White DA, Nortz MJ, Mandernach T, Huntington K, Steiner RD. Deficits in memory strategy use related to prefrontal dysfunction during early development: evidence from children with phenylketonuria. Neuropsychology. 2001 Apr;15(2):221-9. doi: 10.1037//0894-4105.15.2.221.
PubMed 11324865
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Behavioral Effects of Kuvan in Children With Mild Phenylketonuria
- ClinicalTrials.gov ID
- NCT00827762
- Acronym / sponsor ID
- MildPKU/Kuvan/White
- Conditions
- Phenylketonuria
- Keywords
- phenylketonuria, Kuvan, sapropterin, behavior, cognition, executive abilities, attention
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Too few participants recruited within timeframe
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- BioMarin Pharmaceutical, University of Missouri-Columbia, Northwestern University, Oregon Health and Science University
- Study start
- Jan 2009
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 23 Jan 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether improvements in behavior occur in children with phenylketonuria (PKU) who are taking Kuvan.
Detailed description
Little research has been conducted to examine behavior and cognition in children with mild PKU/hyperphenylalanemia, but there is evidence of reductions in general intelligence (IQ) (Costello, 1994) and impairments in executive abilities (Diamond, 1994; Gassio, 2005) in this population. It is important to note that the phenylalanine levels of children with mild PKU are approximately equivalent to those of children with classical PKU whose phenylalanine levels have been managed through dietary control. In children with diet-treated PKU, impairments in behavior and cognition are well-documented, particularly in relation to executive abilities (Christ, 2006; White, 2001, 2002). Taken together, these findings suggest that children with mild PKU are at risk for behavioral and cognitive impairments, and it is possible that these impairments may be mitigated by lowering phenylalanine levels through treatment with Kuvan.
To investigate this issue, approximately 20 children with mild PKU from 6 to 18 years of age (inclusive) and their parents will participate in the study. The behavior and cognition of children with mild PKU will be assessed using the following methods: (1) Parents will complete inventories to rate the behavior and cognition of their children; (2) Older children will complete self-report inventories to rate their behavior and cognition; (3) Cognitive tasks assessing IQ and executive aspects of attention (i.e., sustained attention and inhibitory control) will be administered to all children.
The primary objectives are two-fold. First, we will determine if behavior and cognition are compromised in children with mild PKU prior to treatment with Kuvan (baseline). To accomplish this objective, we will administer measures of behavior and cognition that include normative data based on age. We hypothesize that children with mild PKU will have ratings and scores that are ≥ 1 standard deviation from the normative mean. Second, we will determine if behavior and cognition improve in children with mild PKU following treatment with Kuvan. To accomplish this objective, we will administer the same measures of behavior and cognition after 4 and 24 weeks of treatment with Kuvan(4-week and 24-week follow-ups, respectively). We hypothesize that the follow-up ratings and scores of children with mild PKU will improve by ≥ 0.5 standard deviation relative to their baseline ratings and scores.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phenylketonuria | – | Drug: KuvanIndividuals with mild phenylketonuria/hyperphenylalanemia who are beginning treatment with Kuvan. |
Who may qualify
- Ages
- 6 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Primary care clinic for phenylketonuria.
Key inclusion criteria (7 listed)
- Willing and able to provide informed consent and/or assent.
- Willing and able to comply with study procedures.
- Between 6 and 18 years of age, inclusive.
- Intention of physician to prescribe Kuvan.
- Phenylalanine levels between 360μmol/L and 600μmol/L, inclusive, when untreated with dietary restrictions.
Key exclusion criteria (9 listed)
- Treatment with Kuvan within the past 6 months.
- Pregnant, breastfeeding, or planning to become pregnant during study.
- Use of investigational product less than 30 days prior to or during study.
- Concurrent condition that could interfere with participation or safety.
- Any condition creating high risk of poor compliance with study.
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 |
|---|---|---|
| KuvanAlso: Sapropterin20/mg/kg/day taken once daily or as otherwise prescribed by physician as standard care. | Drug | Phenylketonuria |
Primary outcome
Behavior Rating Inventory of Executive Function (BRIEF)
Time frame: baseline, 4-week follow-up, 24-week follow-up
4 secondary outcomes
Behavior Assessment System for Children - Second Edition (BASC-2)
Time frame: baseline, 4-week follow-up, 24-week follow-up
Conners 3rd Edition (Conners 3)
Time frame: baseline, 4-week follow-up, 24-week follow-up
Conners Continuous Performance Test II Version 5 (CCPT-II Version 5)
Time frame: baseline, 4-week follow-up, 24-week follow-up
Matrix Reasoning subtest of the Wechsler Abbreviated Scale of Intelligence (WASI)
Time frame: baseline, 4-week follow-up, 24-week follow-up
Results and safety
The study was stopped early (reason given: Too few participants recruited within timeframe). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2013.
- Background: PubMed 17083296Christ SE, Steiner RD, Grange DK, Abrams RA, White DA. Inhibitory control in children with phenylketonuria. Dev Neuropsychol. 2006;30(3):845-64. doi: 10.1207/s15326942dn3003_5.
- Background: PubMed 11843066White DA, Nortz MJ, Mandernach T, Huntington K, Steiner RD. Age-related working memory impairments in children with prefrontal dysfunction associated with phenylketonuria. J Int Neuropsychol Soc. 2002 Jan;8(1):1-11.
- Background: PubMed 11324865White DA, Nortz MJ, Mandernach T, Huntington K, Steiner RD. Deficits in memory strategy use related to prefrontal dysfunction during early development: evidence from children with phenylketonuria. Neuropsychology. 2001 Apr;15(2):221-9. doi: 10.1037//0894-4105.15.2.221.
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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.
Desiree White, Ph.D. principal investigator
Washington University School of Medicine
Dorothy K. Grange, M.D. principal investigator
Washington University School of Medicine
4 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 Washington University School of Medicine at 4 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 7 inclusion and 9 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: stopped early, as of the sponsor's last update on 5 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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?
The study was stopped early (reason given: Too few participants recruited within timeframe). Results are not available in the source record.
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?
Behavior Rating Inventory of Executive Function (BRIEF) (time frame: baseline, 4-week follow-up, 24-week follow-up). 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 NCT00827762, which also lists 3 linked publications.
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 5 Dec 2013.