Fluorodeoxyglucose Positron Emission Tomography (FDG PET) Findings in Patients With Phenylketonuria Before and After KUVAN Therapy

NCT00986973 | Completed Results DMC

• 1 other identifier: IRB 09-007154
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this pilot study is to determine if there are any changes in brain glucose metabolism in the gray matter of patients with Phenylketonuria (PKU) and whether administration of Sapropterin (KUVAN) therapy can improve such deficits.

Conditions

Phenylketonuria

Keywords

PKU; BH4; KUVAN; PET scan; Neurodevelopment

Outcome Measures

Primary Outcomes (1)

• Plasma Phenylalanine Level (mg/dl)

  Plasma phenylalanine level (mg/dl) served as the primary means of evaluating brain glucose metabolism before and after sapropterin (KUVAN) therapy. Blood tests for phenylalanine levels (Phe) were collected before and 4 months after sapropterin (KUVAN) therapy. All subjects received KUVAN at a dose of 20/mg/kg/day for four months. The goal was to estimate the change in blood glucose metabolism after treatment with Sapropterin (if any), with the hypothesis that treatment would decrease plasma Phe levels.

  Measurements were obtained at the beginning and conclusion of each study period (baseline and 4 months)

Secondary Outcomes (6)

• Hopkins Verbal Learning Test (HVLT) Total Recall

  Measures were obtained at the beginning and conclusion of each study period (baseline and 4 months)

• Hopkins Verbal Learning Test (HVLT) Delayed Recall

  Measures were obtained at the beginning and conclusion of each study period (baseline and 4 months)

• Paced Auditory Serial Addition Task (PASAT)

  Measures were obtained at the beginning and conclusion of each study period (baseline and 4 months)

• Symbol-Digit Modalities Test (SMTD)

  Measures were obtained at the beginning and conclusion of each study period (baseline and 4 months)

• Wechsler Adult Intelligence Scale (WAIS-IV)-Digit Span

  Measures were obtained at the beginning and conclusion of each study period (baseline and 4 months)

Study Arms (1)

Sapropterin (KUVAN)

EXPERIMENTAL

All subjects will receive Sapropterin (KUVAN) therapy at a dose of 20/mk/kg/day for four months.

Drug: Sapropterin

Interventions

Sapropterin DRUG

All subjects will receive 20 mg/kg/day Sapropterin (KUVAN) for four months. Subjects will be examined with fluorodeoxyglucose positron emission tomography (FDG-PET) brain imaging, physical and neurological exam, blood tests for phenylalanine (Phe) and tyrosine levels, and neuropsychological testing before and 4 months after KUVAN therapy. Subjects Phe and tyrosine levels will be monitored weekly during the study and subjects will keep 3-day diet records to allow for calculation of Phe intake.

Also known as: KUVAN, BH4

Sapropterin (KUVAN)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Males or females over the age of 18 years
• Subject must be able to give independent informed consent
• Girls must have a negative urine pregnancy test and must use an acceptable method of contraception, including abstinence, a barrier method (diaphragm or condom), Depo-Provera, or an oral contraceptive, for the duration of the study.
• Subject must have a confirmed diagnosis of PKU
• Subjects with Phenylalanine (Phe) levels over 10 mg/dL
• Subjects naïve to KUVAN therapy or has not received KUVAN in the 6 months before screening

You may not qualify if:

• Pregnancy
• Cognitive deficits resulting from physical trauma (e.g. subject with history of severe birth trauma).
• Neurologic comorbidities including a history of a stroke or a seizure disorder.
• Laboratory abnormalities that indicate clinically significant hepatic disease Aspartate aminotransferase (AST)\> 2.0 times the upper limit of normal, Alanine transaminase (ALT) \> 2.0 times the upper limit of normal, Prothrombin Time (PT) \> 2.0 times the upper limit of normal, Partial Thromboplastin Time(PTT) \> 2.0 times the upper limit of normal
• Subjects using medications such as steroids, insulin and glucagons that may interfere with the results of PET scan.
• Subjects using medications that inhibit folate metabolism such as methotrexate
• Subjects using medications known to affect nitric oxide-mediated vasorelaxation.
• Subjects using Levodopa
• Treatment with KUVAN in the past 6 months before study entry.
• Treatment with any investigational product in the last 90 days before study entry

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead

Study Sites (1)

Children's Hospital of Philadelphia, Section of Metabolism,PKU program

Philadelphia, Pennsylvania, 19106, United States

Location

MeSH Terms

Conditions

Phenylketonurias

Interventions

sapropterin

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

Due to small sample size, the statistical power of this study is low. While it is useful in exploring potential trends, the results of this pilot study should be cautiously interpreted. Further studies with a larger sample of subjects are needed.

Results Point of Contact

• Title: Dr. Can Ficicioglu
• Organization: The Children's Hospital of Philadelphia

ficicioglu@email.chop.edu

2155905876

Study Officials

• Can Ficicioglu, MD, PhD

  Children's Hospital of Philadelphia,University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2009
• First Posted: September 30, 2009
• Study Start: March 1, 2010
• Primary Completion: July 1, 2011
• Study Completion: September 1, 2011
• Last Updated: June 8, 2015
• Results First Posted: May 12, 2015

Record last verified: 2015-05

Locations

US (1)