The Brain, Neurological Features and Neuropsychological Functioning in Adults With Phenylketonuria: A Pilot Study

• Sponsor: Boston Children's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01917344
• Collaborator: Beth Israel Deaconess Medical Center (Other), Brigham and Women's Hospital (Other)
• Enrollment: 10
• Location: 1
• Arm: 1
• Duration (Months): 10
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

Newborn screening and early treatment prevent the most severe manifestations of phenylketonuria (PKU). However, executive functioning deficits, attention deficit disorder, slow processing speed, and visual-motor problems commonly occur. Many adults with this disorder also suffer depression and anxiety. Using advanced electroencephalogram (EEG) and magnetic resonance imaging (MRI) techniques, including novel MR spectroscopy (MRS) we hope to discover why this distinct constellation of deficits occurs in PKU. Adult subjects with PKU will undergo EEG and comprehensive MRI evaluations, including a novel method of MR spectroscopy to determine brain phenylalanine levels. In addition, they will receive neurological and neuropsychological examinations and dietary evaluation.

Condition or Disease	Intervention/Treatment	Phase
Phenylketonuria	Other: MRI	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: The Brain, Neurological Features and Neuropsychological Functioning in Adults With Phenylketonuria: A Pilot Study
• Study Start Date: Aug 1, 2013
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Other: Adults with PKU MRI, EEG, neuropsychological testing, neurological examination, blood draw, diet diary, physical examination. These activities were performed for the study, but no drug or other interventions took place.	Other: MRI

Outcome Measures

Primary Outcome Measures

1. Phenylalanine Level in the Brain as Determined by MR Spectroscopy and in Blood [During period of evaluation, approximately 8 hours]

   Brain Phe levels (umol/L) using MRI correlated spectroscopy and Blood Phe levels (umol/L) obtained on the same day.

Secondary Outcome Measures

1. Full Scale Intelligence Quotient (IQ) [During period of evaluation, approximately 8 hours]

2. Electroencephalogram (EEG) Findings [During period of evaluation, approximately 8 hours]

3. Volumetric MRI Findings [During period of evaluation, approximately 8 hours]

4. Diffusion Tensor Imaging (DTI) Findings Through MRI [During period of evaluation, approximately 8 hours]

5. Tremor as Determined Through Neurological Evaluation [During period of evaluation, approximately 8 hours]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Adult with classic PKU who has been seen at one of the hospitals collaborating in this study

2. Age 18-55 years

3. Medical Records available that include genotype and blood phenylalanine levels during the first 6 years of life. (We have over 300 patients with PKU with genotypes in our clinic, of whom about half are adults.)

4. Capable of providing informed consent

5. Able to undergo MRI procedures without sedating medication

6. Does not have metal implants

7. Not currently on Kuvan, Large Neutral Amino Acid therapy or involved in any clinical trials.

Exclusion Criteria:

1. Mild PKU or mild hyperphenylalaninemia

2. Less than 18 years old or great than 55 years old

3. No medical records available for the first 6 years of life

4. No record of genotype

5. Not capable of providing informed consent

6. Not able to undergo MRI without sedating medication

7. Has metal implants

8. Currently taking Kuvan, Large Neutral Amino Acid therapy or involved in any clinical trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Boston Children's Hospital	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Boston Children's Hospital
• Beth Israel Deaconess Medical Center
• Brigham and Women's Hospital

Investigators

• Principal Investigator: Susan E Waisbren, PhD, Boston Children's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Susan Waisbren, Susan Waisbren, P.h.D, Boston Children's Hospital
• ClinicalTrials.gov Identifier: NCT01917344
• Other Study ID Numbers: IRB-P00003864
• First Posted: Aug 6, 2013
• Last Update Posted: Jun 19, 2015
• Last Verified: Jun 1, 2015

• Keywords provided by Susan Waisbren, Susan Waisbren, P.h.D, Boston Children's Hospital: Phenylketonuria; MRI; Neuropsychological functioning; Neurological functioning; EEG
• Additional relevant MeSH terms: Phenylketonurias

Study Results

Participant Flow

Recruitment Details	A recruitment letter was sent to adults with PKU who were not enrolled in another clinical trial.

Arm/Group Title	Adults With PKU
Arm/Group Description	MRI, EEG, neuropsychological testing, neurological examination, blood draw, diet diary, physical examination MRI
Period Title: Overall Study
STARTED	10
COMPLETED	9
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Adults With PKU
Arm/Group Description	MRI, EEG, neuropsychological testing, neurological examination, blood draw, diet diary, physical examination MRI
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	10 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29 (5)
Sex: Female, Male (Count of Participants)
Female	5 50%
Male	5 50%
Region of Enrollment (participants) [Number]
United States	10 100%

Outcome Measures

1. Primary Outcome

Title	Phenylalanine Level in the Brain as Determined by MR Spectroscopy and in Blood
Description	Brain Phe levels (umol/L) using MRI correlated spectroscopy and Blood Phe levels (umol/L) obtained on the same day.
Time Frame	During period of evaluation, approximately 8 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Adults With PKU
Arm/Group Description	MRI, EEG, neuropsychological testing, neurological examination, blood draw, diet diary, physical examination MRI
Measure Participants	9
White Matter	130 (38)
Gray Matter	137 (24)
Blood Phe level	961 (378)

2. Secondary Outcome

Title	Full Scale Intelligence Quotient (IQ)
Time Frame	During period of evaluation, approximately 8 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Electroencephalogram (EEG) Findings
Time Frame	During period of evaluation, approximately 8 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Volumetric MRI Findings
Time Frame	During period of evaluation, approximately 8 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Diffusion Tensor Imaging (DTI) Findings Through MRI
Time Frame	During period of evaluation, approximately 8 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Tremor as Determined Through Neurological Evaluation
Time Frame	During period of evaluation, approximately 8 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Two years.
Arm/Group Title	Adults With PKU
Arm/Group Description	MRI, EEG, neuropsychological testing, neurological examination, blood draw, diet diary, physical examination MRI
All Cause Mortality
	Adults With PKU
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Adults With PKU
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Other (Not Including Serious) Adverse Events
	Adults With PKU
	Affected / at Risk (%)	# Events
Total	0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.