Phenylketonuria, Oxidative Stress, and BH4

NCT ID: NCT01395394

Last Updated: 2014-08-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2013-06-30

Brief Summary

The purpose of this study is to see how tetrahydrobiopterin therapy (BH4; also known as sapropterin dihydrochloride or Kuvan) affects measures of oxidative stress and endothelial function in patients with Phenylketonuria (PKU).

Detailed Description

Oxidative stress will be induced by having participants eat a meal in polyunsaturated fats. The investigators will see how participants respond to the meal challenge over the course of 6 hours.

• PKU participants who are currently on BH4 therapy will be evaluated while taking BH4 with the meal at a single study visit.
• PKU participants who did not responded to BH4 therapy will be evaluated twice. At the first study visit the investigators will see how you react to the meal challenge when you are not given BH4. You will be given BH4 for two weeks, then return for a second meal challenge study visit while taking BH4.
• Healthy controls will be evaluated after consuming the meal only (no BH4) at a single study visit.

Conditions

Phenylketonuria

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: NONE

Study Groups

BH4 Non-Responders

Participants in this group have PKU and were deemed unresponsive to the drug. They will attend their first study visit, and proceed through the meal challenge without BH4. They will then take BH4 for 2 weeks. The second meal challenge will be performed with the participant's final dose of BH4.

Group Type: EXPERIMENTAL

Kuvan

Intervention Type: DRUG

Participants in the BH4 Non-Responder group will be given a 20 mg/kg body weight/day dose of Kuvan to take on a daily basis for two weeks. The last dose will be administered at the participant's study visit 2.

Meal Challenge

Intervention Type: OTHER

At each study visit, patients will receive a meal high in polyunsaturated fats that will promote a transitory increase in oxidative stress measures and endothelial dysfunction

Healthy Controls

Participants in this group match an enrolled PKU participant in terms of age, gender, and body mass index class. They will participate in a single study visit and will not be given BH4.

Group Type: EXPERIMENTAL

Meal Challenge

Intervention Type: OTHER

At each study visit, patients will receive a meal high in polyunsaturated fats that will promote a transitory increase in oxidative stress measures and endothelial dysfunction

BH4 Responders

Participants in this group will use their already prescribed BH4 with the meal challenge and be assessed at a single study visit. They will take their prescribed BH4 with the meal.

Group Type: EXPERIMENTAL

Meal Challenge

Intervention Type: OTHER

At each study visit, patients will receive a meal high in polyunsaturated fats that will promote a transitory increase in oxidative stress measures and endothelial dysfunction

Interventions

Kuvan

Participants in the BH4 Non-Responder group will be given a 20 mg/kg body weight/day dose of Kuvan to take on a daily basis for two weeks. The last dose will be administered at the participant's study visit 2.

Intervention Type: DRUG

Meal Challenge

At each study visit, patients will receive a meal high in polyunsaturated fats that will promote a transitory increase in oxidative stress measures and endothelial dysfunction

Intervention Type: OTHER

Other Intervention Names

Sapropterin dihydrochloride; tetrahydrobiopterin; BH4

Eligibility Criteria

Inclusion Criteria

• Have read, understood, and signed this consent form (and assent form, if <18 years old)
• Are between the ages of 10-45 years
• Weigh at least 75 pounds (34 kg)
• Meet group-specific criteria

Exclusion Criteria

• Smoke
• Have any history of cardiovascular disease
• Have hepatic impairment, or demonstrate abnormal baseline liver function lab test results
• Have donated blood within 3 months prior to the study or are anemic as shown by the baseline lab results
• Are unwilling to discontinue dietary supplements (excluding medical food) two weeks prior to their first study visit
• Are currently take medications that will interfere with the interpretation of selected endpoints (such as lipid-lowering medication)
• Are currently pregnant or breastfeeding
• Excluding PKU, have a chronic illness, disorder, or condition (including but not limited to diabetes, hypertension, cancer)
• Have taken any investigational drug (including Kuvan for Kuvan-unresponsive participants & controls) within 3 months prior to the study
• In the opinion of the Investigator, should not be included in the study for any reason, including inability to follow study procedures

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Rani Singh

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rani H Singh, PhD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory University

Decatur, Georgia, United States

Countries

United States

Related Links

http://www.genetics.emory.edu/nutrition/pbos

Study Website

Other Identifiers

IRB00046153

Identifier Type: -

Identifier Source: org_study_id