PhenylketonuriaNCT01924026
Neurocognitive Outcomes in Mild Hyperphenylalaninemia (MHP)MHP Study
An observational study of Phenylketonuria and Mild Hyperphenylalaninemia, run by The Hospital for Sick Children at 1 site in Canada.
Trial summary
Phenylketonuria (PKU) is a genetic disorder known to cause severe reduction in intelligence and deficits in cognitive function; it is associated with an elevated level of Phenylalanine (Phe) in blood. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Phenylketonuria, Mild Hyperphenylalaninemia
- How many people
- 10 participants
- Where
- 1 siteCanada
- Study dates
- Sep 2013to Feb 2016
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Those with mild form of PKU known as mild hyperphenylalaninemia (MHP) and their unaffected siblings who fulfill the inclusion and exclusion criteria.
Who may be able to join
- Male or Female, ≥ 18 years
- Confirmed to have MHP with at least two Phe levels during lifetime of above 360µmol/L and below 600µmol/L, including newborn screening levels (available since 1968 by either bacterial inhibition, enzymatic or tandem mass spectrometry methodology) and via mutation analysis. Those with occasional levels above 600µmol/L will not be excluded provided the majority of available levels fall within the 360-600µmol/L range.
- On an unrestricted diet and not taking medical food. Women who were on dietary or Kuvan® treatment for past pre-conception or pregnancy management will not be excluded
- Willing and able to give consent and comply with study procedures.
Who cannot join
- Subjects on dietary or Kuvan® treatment within the last 12 weeks will be excluded.
- Co-morbidities that may interfere with study participation and/or put the subject at a higher risk of adverse effects.
- Subjects who do not have an unaffected sibling may still participate.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Neuropsychological and Quality of Life Outcomes in Untreated Adults With Mild Hyperphenylalaninemia (MHP)/Phenylketonuria (PKU) With Phenylalanine Levels Between 360 and 600 µmol/L Caused by Phenylalanine Hydroxylase (PAH) Deficiency.
Phenylketonuria (PKU) is a genetic disorder known to cause severe reduction in intelligence and deficits in cognitive function; it is associated with an elevated level of Phenylalanine (Phe) in blood.
Newborn screening and early treatment with restricted protein diet supplemented by a formula of amino-acids will preserve intelligence. In those with the severe form treated from birth, some deficits that affect higher functions of the brain are seen.
Read more
Given this, there is disagreement about how milder forms of this disease should be managed and what level of Phe is safe to be left untreated.
We seek to assess whether higher Phe levels, between 360 and 600µmol/L, are safe with respect to preservation of intelligence and higher cognitive functions.
Read the detailed description
The following personal/medical information will be collected and reviewed:
- Evaluation of current and past medical history, including psychological treatment such as medication and counseling/therapy.
- Mutational analysis for each MHP subject
- Detailed history of educational, employment, relationship, and socioeconomic status/achievements as a measure of successful transition to adulthood
- Diet history, including past treatment with medical food or Sapropterin (Kuvan) for pre-conceptual and pregnancy Phe management
- All available untreated Phe levels, including newborn screening results (where possible) will be collated to calculate lifetime mean Phe level. Age at collections will be recorded separately for each MHP subjects to ensure inclusion of Phe levels beyond infancy
The following clinical investigations will be administered:
- Measurement of Phe and Tyrosine after an overnight fast, via blood spot using tandem mass spectrometry analysis. Blood spot collection will be done at the same time of day for all subjects.
- Physical exam, height and weight measurements
- Food Frequency Questionnaire assessment to estimate typical daily intake of natural protein.
- Self-Report Questionnaires:
- Behavior Rating Inventory of Executive Function (BRIEF)-A
- Beck Anxiety Inventory
- Beck Depression Inventory
- Quality of Life questionnaire
- Neuropsychological Tests assessed by a trained psychologist
An informant BRIEF-A report will be completed for each subject. To ensure consistency in rating, the same informant will be used where possible for the MHP subject and their sibling control (i.e. parents). These questionnaires will be mailed to the informants and returned to the study site via FedEx.
- Conditions
- Phenylketonuria, Mild Hyperphenylalaninemia
- Keywords
- Phenylketonuria, Mild Hyperphenylalaninemia, PKU, MHP
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Affected MHP | With Phe between 360 and 600 micromoles/L | |
| Unaffected Siblings | With normal Phe levels |
What is being measured
The primary outcome is the main question the study is designed to answer.
Executive function
As measured by subtests in Weschler-IV test, and supplemented with assessments from BRIEF-A and CANTAB(computerised cognitive tests by Cambridge Cognition).
Measured: Day 1
Secondary outcomes (2)
Quality of Life
Measured: Day 1
Presence of anxiety and depression
As measured by Beck Anxiety and Depression Inventories
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2013 (estimated)
- Study startSep 2013
- Primary completionFeb 2016
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PhenylketonuriaStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe 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-control
- Time perspective
- Cross-sectional
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- BioMarin Pharmaceutical
- Responsible party
- Principal investigator, Annette Feigenbaum, The Hospital for Sick Children
- Investigators
- Annette Feigenbaum, MD, Principal investigator, The Hospital for Sick ChildrenKomudi Siriwardena, MD, Principal investigator, Stollery Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01924026
- Sponsor's protocol ID
- 1000039726
- Status last verified
- Feb 2016
- First submitted
- 15 May 2013
- Last updated
- 17 Feb 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: in progress- to be decided.
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuropsychological and Quality of Life Outcomes in Untreated Adults With Mild Hyperphenylalaninemia (MHP)/Phenylketonuria (PKU) With Phenylalanine Levels Between 360 and 600 µmol/L Caused by Phenylalanine Hydroxylase (PAH) Deficiency.
- ClinicalTrials.gov ID
- NCT01924026
- Acronym / sponsor ID
- 1000039726
- Conditions
- Phenylketonuria, Mild Hyperphenylalaninemia
- Keywords
- Phenylketonuria, Mild Hyperphenylalaninemia, PKU, MHP
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- BioMarin Pharmaceutical
- Study start
- Sep 2013
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 16 Aug 2013 (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.
Phenylketonuria (PKU) is a genetic disorder known to cause severe reduction in intelligence and deficits in cognitive function; it is associated with an elevated level of Phenylalanine (Phe) in blood.
Newborn screening and early treatment with restricted protein diet supplemented by a formula of amino-acids will preserve intelligence. In those with the severe form treated from birth, some deficits that affect higher functions of the brain are seen.
Given this, there is disagreement about how milder forms of this disease should be managed and what level of Phe is safe to be left untreated.
We seek to assess whether higher Phe levels, between 360 and 600µmol/L, are safe with respect to preservation of intelligence and higher cognitive functions.
Detailed description
The following personal/medical information will be collected and reviewed:
- Evaluation of current and past medical history, including psychological treatment such as medication and counseling/therapy.
- Mutational analysis for each MHP subject
- Detailed history of educational, employment, relationship, and socioeconomic status/achievements as a measure of successful transition to adulthood
- Diet history, including past treatment with medical food or Sapropterin (Kuvan) for pre-conceptual and pregnancy Phe management
- All available untreated Phe levels, including newborn screening results (where possible) will be collated to calculate lifetime mean Phe level. Age at collections will be recorded separately for each MHP subjects to ensure inclusion of Phe levels beyond infancy
The following clinical investigations will be administered:
- Measurement of Phe and Tyrosine after an overnight fast, via blood spot using tandem mass spectrometry analysis. Blood spot collection will be done at the same time of day for all subjects.
- Physical exam, height and weight measurements
- Food Frequency Questionnaire assessment to estimate typical daily intake of natural protein.
- Self-Report Questionnaires:
- Behavior Rating Inventory of Executive Function (BRIEF)-A
- Beck Anxiety Inventory
- Beck Depression Inventory
- Quality of Life questionnaire
- Neuropsychological Tests assessed by a trained psychologist
An informant BRIEF-A report will be completed for each subject. To ensure consistency in rating, the same informant will be used where possible for the MHP subject and their sibling control (i.e. parents). These questionnaires will be mailed to the informants and returned to the study site via FedEx.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Affected MHP | – | –With Phe between 360 and 600 micromoles/L |
| Unaffected Siblings | – | –With normal Phe levels |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Those with mild form of PKU known as mild hyperphenylalaninemia (MHP) and their unaffected siblings who fulfill the inclusion and exclusion criteria.
Key inclusion criteria (4 listed)
- Male or Female, ≥ 18 years
- Confirmed to have MHP with at least two Phe levels during lifetime of above 360µmol/L and below 600µmol/L, including newborn screening levels (available since 1968 by either bacterial inhibition, enzymatic or tandem mass spectrometry methodology) and via mutation analysis. Those with occasional levels above 600µmol/L will not be excluded provided the majority of available levels fall within the 360-600µmol/L range.
- On an unrestricted diet and not taking medical food. Women who were on dietary or Kuvan® treatment for past pre-conception or pregnancy management will not be excluded
- Willing and able to give consent and comply with study procedures.
Key exclusion criteria (3 listed)
- Subjects on dietary or Kuvan® treatment within the last 12 weeks will be excluded.
- Co-morbidities that may interfere with study participation and/or put the subject at a higher risk of adverse effects.
- Subjects who do not have an unaffected sibling may still participate.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Executive function
Time frame: Day 1
As measured by subtests in Weschler-IV test, and supplemented with assessments from BRIEF-A and CANTAB(computerised cognitive tests by Cambridge Cognition).
2 secondary outcomes
Quality of Life
Time frame: Day 1
Presence of anxiety and depression
Time frame: Day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2016.
- Individual participant dataSharing planned: Yes. in progress- to be decided.
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RecruitingPhase 2
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RecruitingPhase 3
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Recruiting
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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.
Annette Feigenbaum, MD principal investigator
The Hospital for Sick Children
Komudi Siriwardena, MD principal investigator
Stollery Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Phenylketonuria and Mild Hyperphenylalaninemia, run by The Hospital for Sick Children at 1 site in Canada.
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 3 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 17 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Executive function (time frame: Day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Feb 2016.