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Trial record 1 of 11 for:    Boston Children's | pku
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MRI Spectroscopy and Neuropsychological Functioning in Phenylketonuria

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03097250
Recruitment Status : Completed
First Posted : March 31, 2017
Last Update Posted : October 19, 2018
Sponsor:
Collaborator:
Brigham and Women's Hospital
Information provided by (Responsible Party):
Susan Waisbren, Boston Children’s Hospital

Brief 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.

Condition or disease
Phenylketonuria

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.

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Study Type : Observational
Actual Enrollment : 10 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: MRI Spectroscopy and Neuropsychological Functioning in Phenylketonuria
Actual Study Start Date : October 25, 2017
Actual Primary Completion Date : July 1, 2018
Actual Study Completion Date : July 1, 2018


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.



Primary Outcome Measures :
  1. Neuropsychological functioning [ Time Frame: 1 day ]
    NIH Toolbox Cognitive Battery

  2. Social/Emotional Outcome [ Time Frame: 1 day ]
    NIH PROMIS Questionnaires (Neuro QoL)

  3. Blood Biomarkers [ Time Frame: 2 days ]
    Phenylalanine and Tyrosine (umol/L)

  4. Brain Biomarkers [ Time Frame: 2 days ]
    Phenylalanine and Tyrosine (umol/L)


Secondary Outcome Measures :
  1. Intellectual Functioning [ Time Frame: 1 day ]
    Full Scale IQ



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03097250


Locations
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United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Boston Children’s Hospital
Brigham and Women's Hospital
Investigators
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Principal Investigator: Susan E Waisbren, PhD Boston Children’s Hospital

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Responsible Party: Susan Waisbren, Psychologist, Boston Children’s Hospital
ClinicalTrials.gov Identifier: NCT03097250    
Other Study ID Numbers: IRB-P00025151
First Posted: March 31, 2017    Key Record Dates
Last Update Posted: October 19, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Susan Waisbren, Boston Children’s Hospital:
PKU
Neuropsychology
MRI
Additional relevant MeSH terms:
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Phenylketonurias
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases