Neuroimaging and Neurocognitive Assessment and Response to Sapropterin Dihydrochloride Treatment in Phenylketonuria (PKU)

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. Identifier: NCT01412437
Recruitment Status : Withdrawn (poor recruitment)
First Posted : August 9, 2011
Last Update Posted : December 17, 2014
Georgetown University
Information provided by (Responsible Party):
Andrea Gropman, Children's Research Institute

Brief Summary:
The investigators will use different types of brain imaging (MRI) in patients with Phenylketonuria (PKU) who are currently not on a strict diet to test the hypothesis that there is improvement in brain circuitry and biochemistry after return to diet and/or sapropterin dihydrochloride (Kuvan).

Condition or disease Intervention/treatment Phase
PKU Dietary Supplement: diet Drug: sapropterin dihydrochloride Not Applicable

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Multimodal Neuroimaging and Neurocognitive Assessment of Biomarkers and Response to Sapropterin Dihydrochloride Treatment in Phenylketonuria
Study Start Date : April 2011
Actual Primary Completion Date : March 2012
Actual Study Completion Date : December 2012

Arm Intervention/treatment
Experimental: Diet
12 participants will be randomized to diet. Phe levels will be followed by blood levels. A dietician will analyze diet for phe content and advise
Dietary Supplement: diet
12 participants will be randomized to diet. Phe levels will be followed by blood levels. A dietician will analyze diet for phe content and advise
Other Name: PKU diet

Experimental: sapropterin dihydrochloride
Intervention: 24 participants will be randomized to receive the drug 10 mg/kg per day. Responders and non responders will remain on drug for four months
Drug: sapropterin dihydrochloride
20 mg/kg for 4 months
Other Name: Biomarin Kuvan

Drug: sapropterin dihydrochloride
Other Name: Kuvan

Primary Outcome Measures :
  1. Neuroimaging biomarkers [ Time Frame: at 4 months ]
    An estimate of the change in white matter damage and biochemistry in participants with PKU after either diet/Kuvan

Secondary Outcome Measures :
  1. Brain biochemistry [ Time Frame: at 4 months ]
    Assessment of cognitive systems abnormalities (by fMRI ) in the participant cohort after diet/Kuvan

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients with PKU identified on Newborn screening and with phe concentration >12mg/dl on the newborn screen
  2. Baseline phe level at study enrollment > 20 mg/dl (this is the level required for inclusion in the study, regardless of the level used to make diagnosis)
  3. Age range: 18-45 years
  4. Able to comply with neuroimaging without requiring sedation (typically requires IQ over 65). The IQ will be checked with the WASI (Weschler Adult scales of intelligence) before determining eligibility
  5. Able to undergo neuroimaging safely (i.e. without presence of ferromagnetic devices)
  6. Subject has ability to follow instructions in English
  7. Female of childbearing age who is sexually active agrees to urine pregnancy test
  8. Availability to come to Washington, DC to participate in this study

Exclusion Criteria:

  1. Age range <18 or >45 years
  2. Inability to comply with neuroimaging without the use of sedation (low IQ or claustrophobic)
  3. Presence of ferromagnetic device(s) that preclude safe imaging including cardiac pacemaker, neural pacemaker, surgical clips in the brain or blood vessels, surgically implanted metal plates, screws or pins, cochlear implants or metal objects in their body
  4. Pregnant female or breastfeeding at screening or planning to become pregnant at any time during the study.
  5. Baseline phe < 20 mg/dl
  6. Currently on Kuvan
  7. History of substance abuse

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 identifier (NCT number): NCT01412437

United States, District of Columbia
Children's Research Institute
Washington, District of Columbia, United States, 20010
Sponsors and Collaborators
Children's Research Institute
Georgetown University
Principal Investigator: Andrea L Gropman, M.D. Children's Research Institute

Responsible Party: Andrea Gropman, Associate Professor, Children's Research Institute Identifier: NCT01412437     History of Changes
Other Study ID Numbers: BMRN 9956
First Posted: August 9, 2011    Key Record Dates
Last Update Posted: December 17, 2014
Last Verified: December 2014

Keywords provided by Andrea Gropman, Children's Research Institute:
sapropterin dihydrochloride

Additional relevant MeSH terms:
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
Anti-Arrhythmia Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents