Phenylketonuria, Oxidative Stress, and BH4

Phase 2TerminatedNCT01395394

Emory University12 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Masking

NONE

Enrollment

Conditions

Phenylketonuria

Interventions

KuvanDRUG

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 ChallengeOTHER

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

Eligibility

Sex: ALLMin age: 10 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Emory University

Decatur, Georgia, United States

Outcomes

Primary Outcomes

Lipid Peroxidation

Markers will be assessed every other hour for each 6-hour study visit. Kuvan responders and healthy controls will only be assessed at one 6-hour study visit. Kuvan non-responders will be assessed at two study visits (a baseline visit, and a visit after two weeks of Kuvan therapy). Values will be assessed groupwise and also assessed for intrapersonal change in the Kuvan non-responsive group. Time frame of participation is estimated at one month.

Time frame: Lipid peroxidation will be measured every other hour for six hours at baseline (study visit 1) for all study groups

C-Reactive Protein (CRP)

Time frame: CRP will be measured every other hour for six hours at baseline (study visit 1) for all study groups and again during a second visit 2 weeks after baseline in BH4 Non-Responders only (study visit 2)

Data from ClinicalTrials.gov

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