Phenylketonuria, Oxidative Stress, and BH4

This study has been terminated.
(Difficulty with recruitment and agreed with Sponsor to report completed data as as case reports)
Information provided by (Responsible Party):
Rani Singh, Emory University Identifier:
First received: June 23, 2011
Last updated: May 21, 2014
Last verified: May 2014

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).

Condition Intervention Phase
Drug: Kuvan
Other: Meal Challenge
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: The Ability of Kuvan® (Sapropterin Dihydrochloride) to Prevent Meal-induced Lipid Peroxidation and Endothelial Dysfunction in Patients With Phenylketonuria: a Pilot Study

Resource links provided by NLM:

Further study details as provided by Emory University:

Primary Outcome Measures:
  • Lipid Peroxidation [ Time Frame: Lipid peroxidation will be measured every other hour for six hours at each study visit ] [ Designated as safety issue: No ]
    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.

Enrollment: 11
Study Start Date: June 2011
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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.
Other Names:
  • Sapropterin dihydrochloride
  • tetrahydrobiopterin
  • BH4
Other: 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
Experimental: 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.
Other: 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
Experimental: 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.
Other: 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

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.

Ages Eligible for Study:   10 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01395394

United States, Georgia
Emory University
Decatur, Georgia, United States, 30033
Sponsors and Collaborators
Emory University
Principal Investigator: Rani H Singh, PhD Emory University
  More Information

Additional Information:
No publications provided

Responsible Party: Rani Singh, Associate Professor, Emory University Identifier: NCT01395394     History of Changes
Other Study ID Numbers: IRB00046153
Study First Received: June 23, 2011
Last Updated: May 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Emory University:
sapropterin dihydrochloride
Oxidative stress

Additional relevant MeSH terms:
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
Metabolic Diseases processed this record on August 20, 2014