Phenylketonuria, Oxidative Stress, and BH4

Emory University

Status and phase: Terminated; Phase 2

Conditions: Phenylketonuria

Treatments: Other: Meal Challenge; Drug: Kuvan

Study type: Interventional

Funder types: Other

Identifiers

NCT01395394

IRB00046153

Details and patient eligibility

About

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).

Full 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.

Enrollment: 12 patients

Sex: All

Ages: 10 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

12 participants in 3 patient groups

BH4 Non-Responders

Experimental group

Description:

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.

Treatment:

Other: Meal Challenge

Drug: Kuvan

Healthy Controls

Experimental group

Description:

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.

Treatment:

Other: Meal Challenge

BH4 Responders

Experimental group

Description:

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.

Treatment:

Other: Meal Challenge