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

    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital

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:

  1. Age 12-25 years
  2. Not currently participating in a clinical trial
  3. Capable of providing informed assent/consent
  4. Able to undergo MRI procedures without sedation
  5. 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).
  6. PKU Group: identified by newborn screening; received treatment within the first 30 days of life
  7. PKU Group: Pre-treatment/off-diet blood Phe concentration at or above 600 umol/L

Exclusion Criteria:

  1. Older than 25 years or younger than 12 years of age.
  2. Currently participating in a clinical trial
  3. Incapable of providing informed assent/consent
  4. Pregnant women will be excluded
  5. Not able to tolerate MRI procedures without sedation
  6. Has metal implants or braces on teeth not compatible with MRI
  7. Has any known contraindication for MRI
  8. PKU Group: Pre-treatment/off-diet blood Phe concentration below 600 umol/L)
  9. 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
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 the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neuropsychological functioning
Time Frame: 1 day
NIH Toolbox Cognitive Battery
1 day
Social/Emotional Outcome
Time Frame: 1 day
NIH PROMIS Questionnaires (Neuro QoL)
1 day
Blood Biomarkers
Time Frame: 2 days
Phenylalanine and Tyrosine (umol/L)
2 days
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.

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

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.

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