PhenylketonuriaNCT03097250
MRI Spectroscopy and Neuropsychological Functioning in Phenylketonuria
An observational study of Phenylketonuria, run by Boston Children's Hospital at 1 site in United States.
Trial summary
This is a study about the relationship of brain biomarkers with neuropsychological functioning in PKU. All participants will undergo MRI spectroscopy, will provide a blood specimen and will receive neuropsychological testing. Read more about this study
- Who is it for?
- Ages 12 to 25 yearsHealthy volunteers can take part
- Conditions the study is for
- Phenylketonuria
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Oct 2017to 1 Jul 2018
- 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 12 to 25 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: This is an observational case-controlled study that will include adolescents and young adults with PKU (ages 12-25) and a matched comparison group of healthy individuals of the same age and sex.
Who may be able to join
- Age 12-25 years
- Not currently participating in a clinical trial
- Capable of providing informed assent/consent
- Able to undergo MRI procedures without sedation
- Does not have metal implants (braces or permanent retainers made of MRI-compatible materials are permitted since we will not be doing procedures, such as DTI, affected by non-ferrous metals).
- PKU Group: identified by newborn screening; received treatment within the first 30 days of life
- PKU Group: Pre-treatment/off-diet blood Phe concentration at or above 600 umol/L
Who cannot join
- Older than 25 years or younger than 12 years of age.
- Currently participating in a clinical trial
- Incapable of providing informed assent/consent
- Pregnant women will be excluded
- Not able to tolerate MRI procedures without sedation
- Has metal implants or braces on teeth not compatible with MRI
Show all 9Show fewer
- Has any known contraindication for MRI
- PKU Group: Pre-treatment/off-diet blood Phe concentration below 600 umol/L)
- PKU Group: Not identified through newborn screening or treatment was initiated after 30 days of life
Trial locations and contacts
1 site in 1 country.
United States1 site
Boston Children's Hospital
Boston, Massachusetts, 02115
About this study
This is a study about the relationship of brain biomarkers with neuropsychological functioning in PKU. All participants will undergo MRI spectroscopy, will provide a blood specimen and will receive neuropsychological testing.
Read the detailed description
Despite newborn screening and early initiation of treatment, many adolescents and adults with PKU experience some degree of neuropsychological dysfunction or mood disturbances. Blood phenylalanine (Phe) levels and low levels of tyrosine (Tyr) only partially explain why some individuals with PKU have these difficulties and others do not. In this study, the investigators will use a new approach involving magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) for measuring brain Phe (and other brain chemicals) in order to determine relationships between brain biomarkers and neuropsychological functioning and mood. Previously, brain Phe and Tyr could not be reliably measured by MRS methods, especially in concentrations likely to be found in individuals with treated PKU. This project will use an improved method for measuring brain Phe and Tyr. The investigators will use two-dimensional shift correlated magnetic resonance spectroscopy (COSY). COSY is a non-invasive method that allows for quantitative measurement of Phe, Tyr and other amino acids in the brain. This project has the potential to close one of the most important gaps in the knowledge of PKU, namely to define how PKU affects the brain. The aims of this study are to examine brain Phe and Tyr in individuals with PKU and in an age-matched healthy comparison group, and 2) determine the association of Phe and Tyr in distinct brain regions with measures of neuropsychological functioning and mood. Participants with PKU will receive 2 MRI scans with spectroscopy and the comparison group will receive 1 MRI scan with spectroscopy under fasting conditions. All participants will provide a blood specimen for blood amino acid determinations and will receive neuropsychological testing. The investigators will develop statistical models that can be applied in future studies to enhance understanding of PKU. This pilot study is important because it will provide evidence of the usefulness of COSY. COSY has the potential to explain individual differences in PKU, identify specific cognitive functions or mood disturbances related to high brain Phe or low brain Tyr, and offer an additional marker or endpoint for evaluating new treatments in clinical trials.
- Conditions
- Phenylketonuria
- Keywords
- PKU, Neuropsychology, MRI
- 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 |
|---|---|---|
| PKU Subjects | Subjects with PKU will be asked to undergo an MRI and blood draw on Day 1 and Day 2 of the study. They will also receive neuropsychological testing on Day 1 of the study | |
| Controls | Controls will undergo only one MRI and blood draw on Day 1 of the study. They will also receive neuropsychological testing on Day 1 of the study. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neuropsychological functioning
NIH Toolbox Cognitive Battery
Measured: 1 day
Social/Emotional Outcome
NIH PROMIS Questionnaires (Neuro QoL)
Measured: 1 day
Blood Biomarkers
Phenylalanine and Tyrosine (umol/L)
Measured: 2 days
Brain Biomarkers
Phenylalanine and Tyrosine (umol/L)
Measured: 2 days
Secondary outcomes (1)
Intellectual Functioning
Full Scale IQ
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2017
- Study start25 Oct 2017
- Primary completion1 Jul 2018
- Study completion1 Jul 2018
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 Boston Children's HospitalThe 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
- Prospective
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Brigham and Women's Hospital
- Responsible party
- Principal investigator, Susan Waisbren, Boston Children's Hospital
- Investigators
- Susan E Waisbren, PhD, Principal investigator, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03097250
- Sponsor's protocol ID
- IRB-P00025151
- Status last verified
- Oct 2018
- First submitted
- 22 Mar 2017
- Last updated
- 19 Oct 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MRI Spectroscopy and Neuropsychological Functioning in Phenylketonuria
- ClinicalTrials.gov ID
- NCT03097250
- Acronym / sponsor ID
- IRB-P00025151
- Conditions
- Phenylketonuria
- Keywords
- PKU, Neuropsychology, MRI
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Collaborators
- Brigham and Women's Hospital
- Study start
- 25 Oct 2017 (actual)
- Primary completion
- 1 Jul 2018 (actual)
- Study completion
- 1 Jul 2018 (actual)
- First posted
- 31 Mar 2017 (actual)
- 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.
This is a study about the relationship of brain biomarkers with neuropsychological functioning in PKU. All participants will undergo MRI spectroscopy, will provide a blood specimen and will receive neuropsychological testing.
Detailed description
Despite newborn screening and early initiation of treatment, many adolescents and adults with PKU experience some degree of neuropsychological dysfunction or mood disturbances. Blood phenylalanine (Phe) levels and low levels of tyrosine (Tyr) only partially explain why some individuals with PKU have these difficulties and others do not. In this study, the investigators will use a new approach involving magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) for measuring brain Phe (and other brain chemicals) in order to determine relationships between brain biomarkers and neuropsychological functioning and mood. Previously, brain Phe and Tyr could not be reliably measured by MRS methods, especially in concentrations likely to be found in individuals with treated PKU. This project will use an improved method for measuring brain Phe and Tyr. The investigators will use two-dimensional shift correlated magnetic resonance spectroscopy (COSY). COSY is a non-invasive method that allows for quantitative measurement of Phe, Tyr and other amino acids in the brain. This project has the potential to close one of the most important gaps in the knowledge of PKU, namely to define how PKU affects the brain. The aims of this study are to examine brain Phe and Tyr in individuals with PKU and in an age-matched healthy comparison group, and 2) determine the association of Phe and Tyr in distinct brain regions with measures of neuropsychological functioning and mood. Participants with PKU will receive 2 MRI scans with spectroscopy and the comparison group will receive 1 MRI scan with spectroscopy under fasting conditions. All participants will provide a blood specimen for blood amino acid determinations and will receive neuropsychological testing. The investigators will develop statistical models that can be applied in future studies to enhance understanding of PKU. This pilot study is important because it will provide evidence of the usefulness of COSY. COSY has the potential to explain individual differences in PKU, identify specific cognitive functions or mood disturbances related to high brain Phe or low brain Tyr, and offer an additional marker or endpoint for evaluating new treatments in clinical trials.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PKU Subjects | – | –Subjects with PKU will be asked to undergo an MRI and blood draw on Day 1 and Day 2 of the study. They will also receive neuropsychological testing on Day 1 of the study |
| Controls | – | –Controls will undergo only one MRI and blood draw on Day 1 of the study. They will also receive neuropsychological testing on Day 1 of the study. |
Who may qualify
- Ages
- 12 to 25 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- This is an observational case-controlled study that will include adolescents and young adults with PKU (ages 12-25) and a matched comparison group of healthy individuals of the same age and sex.
Key inclusion criteria (7 listed)
- Age 12-25 years
- Not currently participating in a clinical trial
- Capable of providing informed assent/consent
- Able to undergo MRI procedures without sedation
- Does not have metal implants (braces or permanent retainers made of MRI-compatible materials are permitted since we will not be doing procedures, such as DTI, affected by non-ferrous metals).
Key exclusion criteria (9 listed)
- Older than 25 years or younger than 12 years of age.
- Currently participating in a clinical trial
- Incapable of providing informed assent/consent
- Pregnant women will be excluded
- Not able to tolerate MRI procedures without sedation
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
Neuropsychological functioning
Time frame: 1 day
NIH Toolbox Cognitive Battery
Social/Emotional Outcome
Time frame: 1 day
NIH PROMIS Questionnaires (Neuro QoL)
Blood Biomarkers
Time frame: 2 days
Phenylalanine and Tyrosine (umol/L)
Brain Biomarkers
Time frame: 2 days
Phenylalanine and Tyrosine (umol/L)
1 secondary outcome
Intellectual Functioning
Time frame: 1 day
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 19 Oct 2018.
- Individual participant dataSharing planned: No
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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.
Susan E Waisbren, PhD principal investigator
Boston 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, run by Boston Children's Hospital at 1 site 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: finished, as of the sponsor's last update on 19 Oct 2018. 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 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 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?
Neuropsychological functioning (time frame: 1 day). The study lists 4 primary outcomes in all. 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 19 Oct 2018.