Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03097250
Other study ID # IRB-P00025151
Secondary ID
Status Completed
Phase
First received
Last updated
Start date October 25, 2017
Est. completion date July 1, 2018

Study information

Verified date October 2018
Source Boston Children’s Hospital
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 10
Est. completion date July 1, 2018
Est. primary completion date July 1, 2018
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 12 Years to 25 Years
Eligibility 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 Design


Related Conditions & MeSH terms


Locations

Country Name City State
United States Boston Children's Hospital Boston Massachusetts

Sponsors (2)

Lead Sponsor Collaborator
Boston Children’s Hospital Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Neuropsychological functioning NIH Toolbox Cognitive Battery 1 day
Primary Social/Emotional Outcome NIH PROMIS Questionnaires (Neuro QoL) 1 day
Primary Blood Biomarkers Phenylalanine and Tyrosine (umol/L) 2 days
Primary Brain Biomarkers Phenylalanine and Tyrosine (umol/L) 2 days
Secondary Intellectual Functioning Full Scale IQ 1 day
See also
  Status Clinical Trial Phase
Completed NCT05099640 - A Study of PTC923 in Participants With Phenylketonuria Phase 3
Completed NCT01924026 - Neurocognitive Outcomes in Mild Hyperphenylalaninemia (MHP)MHP Study N/A
Completed NCT01428258 - Phase 2 Study of Glycomacropeptide Versus Amino Acid Diet for Management of Phenylketonuria N/A
Completed NCT00925054 - Dose-Finding Study to Evaluate the Safety, Efficacy, & Tolerability of Multiple Doses of rAvPAL-PEG in Subjects With PKU Phase 2
Completed NCT00778206 - PKUDOS: Phenylketonuria (PKU) Demographic, Outcomes, and Safety Registry
Recruiting NCT05948020 - Efficacy and Safety of Orally Administered Engineered Probiotics (CBT102-A) for the Treatment of Children With Phenylketonuria N/A
Recruiting NCT05781399 - First-in-Human, Multiple Part Clinical Study of JNT-517 in Healthy Participants and in Participants With Phenylketonuria Phase 1
Completed NCT02555579 - Simplified Diet Approach in Phenylketonuria N/A
Completed NCT01965912 - Kuvan®'s Effect on the Cognition of Children With Phenylketonuria Phase 4
Completed NCT01965691 - Protein Requirements in Children With Phenylketonuria (PKU) N/A
Completed NCT00688844 - Nutritional and Neurotransmitter Changes in PKU Subjects on BH4 N/A
Completed NCT00789568 - A Phase 1 Study to Evaluate Effects of Sapropterin Dihydrochloride on QTc Intervals in Healthy Adult Subjects Phase 1
Terminated NCT01465100 - Liver Cell Transplant for Phenylketonuria Phase 1/Phase 2
Completed NCT01732471 - Phase 3 Open-label Study to Evaluate the Response and Safety of Kuvan® in Subjects With Phenylketonuria Phase 3
Completed NCT04879277 - Study of Low-grade Systemic Inflammation in Adult Patients With Phenylketonuria N/A
Completed NCT02176603 - Observational Study of Endothelial Dysfunction in Phenylketonuria N/A
Completed NCT01819727 - An Open-Label Phase 3 Study of BMN 165 for Adults With PKU Not Previously Treated w/ BMN 165 Phase 3
Completed NCT01869972 - Biological Variation of Phenylalanine in Patients With Hyperphenylalaninemia N/A
Terminated NCT01904708 - Moderate Intensity Exercise and Phenylketonuria N/A
Completed NCT01560286 - A Study to Evaluate Subcutaneously Administered rAvPAL-PEG in Patients With Phenylketonuria for 24 Weeks Phase 2