ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 11 of 81 for:    "phenylketonuria"

Phenylketonuria, Oxidative Stress, and BH4

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.
ClinicalTrials.gov Identifier: NCT01395394
Recruitment Status : Terminated (Difficulty with recruitment and agreed with Sponsor to report completed data as case reports)
First Posted : July 15, 2011
Results First Posted : August 28, 2014
Last Update Posted : August 28, 2014
Sponsor:
Information provided by (Responsible Party):
Rani Singh, Emory University

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label)
Condition Phenylketonuria
Interventions Drug: Kuvan
Other: Meal Challenge
Enrollment 12

Recruitment Details  
Pre-assignment Details  
Arm/Group Title BH4 Non-Responders Healthy Controls BH4 Responders
Hide Arm/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.

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

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

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

Period Title: Baseline Study Visit
Started 4 3 5
Completed 3 3 5
Not Completed 1 0 0
Reason Not Completed
Protocol Violation             1             0             0
Period Title: Study Visit 2 (Non-responders Only)
Started 3 0 0
Completed 3 0 0
Not Completed 0 0 0
Arm/Group Title BH4 Non-Responders Healthy Controls BH4 Responders Total
Hide Arm/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.

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

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

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 of all reporting groups
Overall Number of Baseline Participants 4 3 5 12
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4 participants 3 participants 5 participants 12 participants
33.9  (13.4) 33.5  (15.7) 18.5  (3.8) 27.4  (12.6)
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 3 participants 5 participants 12 participants
<=18 years
1
  25.0%
1
  33.3%
2
  40.0%
4
  33.3%
Between 18 and 65 years
3
  75.0%
2
  66.7%
3
  60.0%
8
  66.7%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 3 participants 5 participants 12 participants
Female
1
  25.0%
1
  33.3%
0
   0.0%
2
  16.7%
Male
3
  75.0%
2
  66.7%
5
 100.0%
10
  83.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 4 participants 3 participants 5 participants 12 participants
4 3 5 12
high-sensitivity CRP  
Mean (Standard Deviation)
Unit of measure:  mg/L
Number Analyzed 4 participants 3 participants 5 participants 12 participants
1.3  (1.2) 0.61  (0.14) 1.04  (1.48) 1.06  (1.19)
1.Primary Outcome
Title Lipid Peroxidation
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Study was terminated due to difficulty recruiting patients, thus analysis was limited to preliminary data on 11 patients only. TBARS was measured in 3 BH4 responders only - data were unavailable for 8 other participants (2 responders, 3 non-responders, and 3 controls) due to inadequate sample volume.
Arm/Group Title BH4 Non-Responders Healthy Controls BH4 Responders
Hide Arm/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.

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

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

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

Overall Number of Participants Analyzed 0 0 3
Mean (Standard Deviation)
Unit of Measure: umole/L
Baseline (prior to meal challenge) 0.57  (0.33)
2-hours post meal 0.62  (0.53)
4-hours post meal 0.73  (0.39)
6-hours post meal 0.78  (0.47)
2.Primary Outcome
Title C-Reactive Protein (CRP)
Hide Description 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 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Study was terminated due to difficulty recruiting patients, thus analysis was limited to preliminary data on 11 patients only. CRP was measured in 10 subjects - data were unavailable for 1 control participant due to inadequate sample volume.
Arm/Group Title BH4 Non-Responders Healthy Controls BH4 Responders
Hide Arm/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.

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

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

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

Overall Number of Participants Analyzed 3 2 5
Mean (Standard Deviation)
Unit of Measure: mg/dl
Baseline, prior to meal challenge (n=3, 2, 5) 1.46  (1.47) 0.61  (0.14) 1.04  (1.48)
2-hours post meal (n=3, 2, 5) 1.50  (1.49) 0.58  (0.12) 0.99  (1.40)
4-hours post meal (n=3, 2, 5) 1.55  (1.50) 0.55  (0.18) 0.96  (1.33)
6-hours post meal (n=3, 2, 5) 1.59  (1.60) 0.55  (0.11) 0.90  (1.24)
Baseline V2, prior to meal challenge (n=3, 0, 0) 1.51  (1.56) NA [1]   (NA) NA [2]   (NA)
2-hours post meal (V2; n=3, 0, 0) 1.55  (1.67) NA [1]   (NA) NA [2]   (NA)
4-hours post meal (V2; n=3, 0, 0) 1.79  (2.11) NA [1]   (NA) NA [2]   (NA)
6-hours post meal (V2; n=3, 0, 0) 1.58  (1.69) NA [1]   (NA) NA [2]   (NA)
[1]
Controls did not complete Study Visit 2
[2]
BH4 Responders did not complete Study Visit 2
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title BH4 Non-Responders Healthy Controls BH4 Responders
Hide Arm/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.

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

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

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

All-Cause Mortality
BH4 Non-Responders Healthy Controls BH4 Responders
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
BH4 Non-Responders Healthy Controls BH4 Responders
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/4 (0.00%)   0/3 (0.00%)   0/5 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
BH4 Non-Responders Healthy Controls BH4 Responders
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/4 (0.00%)   0/3 (0.00%)   0/5 (0.00%) 
Early termination leading to small number of subjects analyzed.
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
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