Phenylketonuria, Oxidative Stress, and BH4

NCT01395394 | Terminated Phase 2 Results DMC

• 1 other identifier: IRB00046153
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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).

Conditions

Phenylketonuria

Keywords

Phenylketonuria; PKU; tetrahydrobiopterin; sapropterin dihydrochloride; BH4; Kuvan; Oxidative stress

Outcome Measures

Primary Outcomes (2)

• 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.

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

• C-Reactive Protein (CRP)

  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.

  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)

Study Arms (3)

BH4 Non-Responders

EXPERIMENTAL

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; Other: Meal Challenge

Healthy Controls

EXPERIMENTAL

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

BH4 Responders

EXPERIMENTAL

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

Interventions

Kuvan 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.

Also known as: Sapropterin dihydrochloride, tetrahydrobiopterin, BH4

BH4 Non-Responders

Meal Challenge 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 Non-Responders; BH4 Responders; Healthy Controls

Eligibility Criteria

• Age: 10 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Emory University

Decatur, Georgia, 30033, United States

Location

Related Links

• Study Website

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

Early termination leading to small number of subjects analyzed.

Results Point of Contact

• Title: Kathryn Coakley
• Organization: Emory University

kcoakle@emory.edu

404-778-1286

Study Officials

• Rani H Singh, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 23, 2011
• First Posted: July 15, 2011
• Study Start: June 1, 2011
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: August 28, 2014
• Results First Posted: August 28, 2014

Record last verified: 2014-08

Locations

US (1)