- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03097250
MRI Spectroscopy and Neuropsychological Functioning in Phenylketonuria
October 18, 2018 updated by: Susan Waisbren, Boston Children's Hospital
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.
Study Overview
Status
Completed
Conditions
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 Type
Observational
Enrollment (Actual)
10
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Boston Children's Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
12 years to 25 years (Child, Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Sampling Method
Non-Probability Sample
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.
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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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
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Neuropsychological functioning
Time Frame: 1 day
|
NIH Toolbox Cognitive Battery
|
1 day
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Social/Emotional Outcome
Time Frame: 1 day
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NIH PROMIS Questionnaires (Neuro QoL)
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1 day
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Blood Biomarkers
Time Frame: 2 days
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Phenylalanine and Tyrosine (umol/L)
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2 days
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Brain Biomarkers
Time Frame: 2 days
|
Phenylalanine and Tyrosine (umol/L)
|
2 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Intellectual Functioning
Time Frame: 1 day
|
Full Scale IQ
|
1 day
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 25, 2017
Primary Completion (Actual)
July 1, 2018
Study Completion (Actual)
July 1, 2018
Study Registration Dates
First Submitted
March 22, 2017
First Submitted That Met QC Criteria
March 27, 2017
First Posted (Actual)
March 31, 2017
Study Record Updates
Last Update Posted (Actual)
October 19, 2018
Last Update Submitted That Met QC Criteria
October 18, 2018
Last Verified
October 1, 2018
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB-P00025151
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Phenylketonuria
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Vitaflo International, LtdUniversity College London HospitalsRecruiting
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BioMarin PharmaceuticalRecruitingPhenylketonuria (PKU)United States, Germany, Italy
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Nutricia ResearchCompleted
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BioMarin PharmaceuticalActive, not recruiting
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BioMarin PharmaceuticalCompletedPhenylketonuria (PKU)United States, Turkey, Canada, France, Germany, Italy, United Kingdom
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Washington University School of MedicineUniversity of Missouri-Columbia; Northwestern University; Oregon Health and Science... and other collaboratorsTerminated
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BioMarin PharmaceuticalRecruitingPhenylketonuria (PKU)United States
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University of Southern CaliforniaBioMarin PharmaceuticalCompleted
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Stanford UniversityBioMarin PharmaceuticalWithdrawnClassical Phenylketonuria(PKU)
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University of ZurichCompletedPhenylketonuria (PKU) and HyperphenylalaninemiaSwitzerland