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Phenylketonuria, Oxidative Stress, and BH4

This study has been terminated.
(Difficulty with recruitment and agreed with Sponsor to report completed data as case reports)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01395394
First Posted: July 15, 2011
Last Update Posted: August 28, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Rani Singh, Emory University
Results First Submitted: July 30, 2014  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label)
Condition: Phenylketonuria
Interventions: Drug: Kuvan
Other: Meal Challenge

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
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.

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.

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

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.

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

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.

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


Participant Flow for 2 periods

Period 1:   Baseline Study Visit
    BH4 Non-Responders   Healthy Controls   BH4 Responders
STARTED   4   3   5 
COMPLETED   3   3   5 
NOT COMPLETED   1   0   0 
Protocol Violation                1                0                0 

Period 2:   Study Visit 2 (Non-responders Only)
    BH4 Non-Responders   Healthy Controls   BH4 Responders
STARTED   3   0   0 
COMPLETED   3   0   0 
NOT COMPLETED   0   0   0 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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.

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.

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

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.

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

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.

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

Total Total of all reporting groups

Baseline Measures
   BH4 Non-Responders   Healthy Controls   BH4 Responders   Total 
Overall Participants Analyzed 
[Units: Participants]
 4   3   5   12 
Age 
[Units: Years]
Mean (Standard Deviation)
 33.9  (13.4)   33.5  (15.7)   18.5  (3.8)   27.4  (12.6) 
Age 
[Units: Participants]
       
<=18 years   1   1   2   4 
Between 18 and 65 years   3   2   3   8 
>=65 years   0   0   0   0 
Gender 
[Units: Participants]
       
Female   1   1   0   2 
Male   3   2   5   10 
Region of Enrollment 
[Units: Participants]
       
United States   4   3   5   12 
high-sensitivity CRP 
[Units: mg/L]
Mean (Standard Deviation)
 1.3  (1.2)   0.61  (0.14)   1.04  (1.48)   1.06  (1.19) 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Lipid Peroxidation   [ Time Frame: Lipid peroxidation will be measured every other hour for six hours at baseline (study visit 1) for all study groups ]

2.  Primary:   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) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Early termination leading to small number of subjects analyzed.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Kathryn Coakley
Organization: Emory University
phone: 404-778-1286
e-mail: kcoakle@emory.edu



Responsible Party: Rani Singh, Emory University
ClinicalTrials.gov Identifier: NCT01395394     History of Changes
Other Study ID Numbers: IRB00046153
First Submitted: June 23, 2011
First Posted: July 15, 2011
Results First Submitted: July 30, 2014
Results First Posted: August 28, 2014
Last Update Posted: August 28, 2014