Neuroimaging and Neurocognitive Assessment and Response to Sapropterin Dihydrochloride Treatment in Phenylketonuria

NCT01412437 | Withdrawn DMC

• 1 other identifier: BMRN 9956
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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).

Conditions

PKU

Keywords

PKU; MRI; neurocognition; sapropterin dihydrochloride

Outcome Measures

Primary Outcomes (1)

• Neuroimaging biomarkers

  An estimate of the change in white matter damage and biochemistry in participants with PKU after either diet/Kuvan

  at 4 months

Secondary Outcomes (1)

• Brain biochemistry

  at 4 months

Study Arms (2)

Diet

EXPERIMENTAL

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

sapropterin dihydrochloride

EXPERIMENTAL

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

Interventions

diet DIETARY_SUPPLEMENT

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

Also known as: PKU diet

Diet

sapropterin dihydrochloride DRUG

20 mg/kg for 4 months

Also known as: Biomarin Kuvan

sapropterin dihydrochloride

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients with PKU identified on Newborn screening and with phe concentration \>12mg/dl on the newborn screen
• Age range: 18-45 years
• 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
• Able to undergo neuroimaging safely (i.e. without presence of ferromagnetic devices)
• Subject has ability to follow instructions in English
• Female of childbearing age who is sexually active agrees to urine pregnancy test
• Availability to come to Washington, DC to participate in this study

You may not qualify if:

• Age range \<18 or \>45 years
• Inability to comply with neuroimaging without the use of sedation (low IQ or claustrophobic)
• 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
• Pregnant female or breastfeeding at screening or planning to become pregnant at any time during the study.
• Baseline phe \< 20 mg/dl
• Currently on Kuvan
• History of substance abuse

Sponsors & Collaborators

• Children's National Research Institute: lead
• Georgetown University: collaborator

Study Sites (1)

Children's Research Institute

Washington D.C., District of Columbia, 20010, United States

Location

Related Publications (1)

• Christ SE, Moffitt AJ, Peck D. Disruption of prefrontal function and connectivity in individuals with phenylketonuria. Mol Genet Metab. 2010;99 Suppl 1:S33-40. doi: 10.1016/j.ymgme.2009.09.014.

  PMID: 20123468 BACKGROUND

MeSH Terms

Interventions

Diet; sapropterin

Intervention Hierarchy (Ancestors)

Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Andrea L Gropman, M.D.

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 1, 2011
• First Posted: August 9, 2011
• Study Start: April 1, 2011
• Primary Completion: March 1, 2012
• Study Completion: December 1, 2012
• Last Updated: December 17, 2014

Record last verified: 2014-12

Locations

US (1)