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Nutritional and Neurotransmitter Changes in PKU Subjects on BH4 (BH4&PKU)

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: NCT00688844
Recruitment Status : Completed
First Posted : June 3, 2008
Results First Posted : August 20, 2014
Last Update Posted : June 8, 2015
Sponsor:
Collaborators:
BioMarin Pharmaceutical
Atlanta Clinical and Translational Science Institute
Information provided by (Responsible Party):
Rani Singh, Emory University

Study Type Observational
Study Design Observational Model: Cohort;   Time Perspective: Prospective
Condition Phenylketonuria
Intervention Drug: KuvanTM Therapy
Enrollment 58
Recruitment Details Recruitment lasted 1 year from October 2008 - October 2009. Recruitment occurred at the Emory University Genetics Clinic, Department of Human Genetics in Decatur, GA.
Pre-assignment Details There were no exclusions of subjects once enrolled.
Arm/Group Title Subjects With Phenylketonuria Starting Sapropterin Therapy
Hide Arm/Group Description Subjects with Phenylketonuria starting sapropterin therapy for the purpose of lowering blood phenylalanine levels.
Period Title: Overall Study
Started 58
Completed 48
Not Completed 10
Reason Not Completed
Lost to Follow-up             10
Arm/Group Title Subjects With Phenylketonuria Starting Sapropterin Therapy
Hide Arm/Group Description Subjects with Phenylketonuria starting sapropterin therapy for the purpose of lowering blood phenylalanine levels.
Overall Number of Baseline Participants 58
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants
<=18 years
38
  65.5%
Between 18 and 65 years
20
  34.5%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 58 participants
17  (11)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants
Female
24
  41.4%
Male
34
  58.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 58 participants
58
1.Primary Outcome
Title Change From Baseline in BMI at 12 Months
Hide Description Change in Body mass index (BMI) from baseline of Kuvan study to 12 months post-baseline
Time Frame Baseline and 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Data missing for 2 participants
Arm/Group Title Subjects With Phenylketonuria Starting Sapropterin Therapy
Hide Arm/Group Description:
Subjects with Phenylketonuria starting sapropterin therapy for the purpose of lowering blood phenylalanine levels.
Overall Number of Participants Analyzed 46
Mean (Standard Deviation)
Unit of Measure: kg/m^2
-0.65574  (8.060658)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Subjects With Phenylketonuria Starting Sapropterin Therapy
Comments Objective was to evaluate BMI across one year in PKU patients introduced to sapropterin after baseline. Study was prospective cohort in design.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.692782
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.655574
Parameter Dispersion
Type: Standard Deviation
Value: 8.060658
Estimation Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline in Bone Mineral Density (BMD) at 12 Months
Hide Description Change in bone mineral density (BMD) from baseline of Kuvan study to 12 months post-baseline
Time Frame Baseline and 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Data missing for 3 participants
Arm/Group Title Subjects With Phenylketonuria Starting Sapropterin Therapy
Hide Arm/Group Description:
Subjects with Phenylketonuria starting sapropterin therapy for the purpose of lowering blood phenylalanine levels.
Overall Number of Participants Analyzed 45
Mean (Standard Deviation)
Unit of Measure: grams/centimeter^2
0.005401  (0.0243)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Subjects With Phenylketonuria Starting Sapropterin Therapy
Comments Objective was to evaluate total body bone mineral density (BMD) one year via DXA in PKU patients introduced to sapropterin after baseline. Study was prospective cohort in design.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.005401
Parameter Dispersion
Type: Standard Deviation
Value: 0.0243
Estimation Comments [Not Specified]
3.Primary Outcome
Title Change From Baseline in Percent (%) Lean Mass at 12 Months
Hide Description % lean mass was measured via dual energy x-ray absorptiometry (DXA)
Time Frame Baseline and 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Data missing for 3 participants
Arm/Group Title Subjects With Phenylketonuria Starting Sapropterin Therapy
Hide Arm/Group Description:
Subjects with Phenylketonuria starting sapropterin therapy for the purpose of lowering blood phenylalanine levels.
Overall Number of Participants Analyzed 45
Mean (Standard Deviation)
Unit of Measure: Percent Lean Mass
2.419224  (3.4666)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Subjects With Phenylketonuria Starting Sapropterin Therapy
Comments Objective was to evaluate % lean mass across one year via DXA in PKU patients introduced to sapropterin after baseline. Study was prospective cohort in design.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.017941
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.419224
Parameter Dispersion
Type: Standard Deviation
Value: 3.4666
Estimation Comments [Not Specified]
4.Primary Outcome
Title Change From Baseline in Percent (%) Fat Mass at 12 Months
Hide Description Percent fat mass measured via dual energy x-ray absorptiometry (DXA)
Time Frame Baseline and 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Data missing for 3 participants
Arm/Group Title Subjects With Phenylketonuria Starting Sapropterin Therapy
Hide Arm/Group Description:
Subjects with Phenylketonuria starting sapropterin therapy for the purpose of lowering blood phenylalanine levels.
Overall Number of Participants Analyzed 45
Mean (Standard Deviation)
Unit of Measure: Percent Fat Mass
1.208889  (3.519867)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Subjects With Phenylketonuria Starting Sapropterin Therapy
Comments Objective was to evaluate % fat mass across one year via DXA in PKU patients introduced to sapropterin after baseline. Study was prospective cohort in design.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.026009
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.208889
Parameter Dispersion
Type: Standard Deviation
Value: 3.51967
Estimation Comments [Not Specified]
5.Primary Outcome
Title Change From Baseline in Plasma Phenylalanine at 12 Months
Hide Description Full amino acid panel, including phenylalanine, analyzed in fasting plasma samples.
Time Frame Baseline and 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Subjects With Phenylketonuria Starting Sapropterin Therapy
Hide Arm/Group Description:
Subjects with Phenylketonuria starting sapropterin therapy for the purpose of lowering blood phenylalanine levels.
Overall Number of Participants Analyzed 48
Mean (Standard Deviation)
Unit of Measure: Micromoles per liter
-67.5187  (362.9412)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Subjects With Phenylketonuria Starting Sapropterin Therapy
Comments Objective was to evaluate plasma phenylalanine across one year in PKU patients introduced to sapropterin after baseline. Study was prospective cohort in design.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.303864
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -67.5187
Parameter Dispersion
Type: Standard Deviation
Value: 362.9412
Estimation Comments [Not Specified]
6.Primary Outcome
Title Change From Baseline in Total Dietary Protein Intake at 12 Months
Hide Description Total dietary protein intake assessed through 3-day food records - calculated as average protein intake (grams/day) in the 3 days recorded
Time Frame Baseline and 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Dietary intake not submitted by 11 participants at 12 months.
Arm/Group Title Subjects With Phenylketonuria Starting Sapropterin Therapy
Hide Arm/Group Description:
Subjects with Phenylketonuria starting sapropterin therapy for the purpose of lowering blood phenylalanine levels.
Overall Number of Participants Analyzed 37
Mean (Standard Deviation)
Unit of Measure: grams per day
-10.9549  (20.10814)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Subjects With Phenylketonuria Starting Sapropterin Therapy
Comments Objective was to evaluate protein intake (grams per day) across one year in PKU patients introduced to sapropterin after baseline. Study was prospective cohort in design.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00088
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -10.9549
Parameter Dispersion
Type: Standard Deviation
Value: 20.10814
Estimation Comments [Not Specified]
7.Primary Outcome
Title Change From Baseline in Phenylalanine Intake at 12 Months
Hide Description Total dietary phenylalanine assessed through 3-day food records - calculated as average phenylalanine intake (grams/day) in the 3 days recorded
Time Frame Baseline and 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Dietary intake not submitted by 11 participants at 12 months.
Arm/Group Title Subjects With Phenylketonuria Starting Sapropterin Therapy
Hide Arm/Group Description:
Subjects with Phenylketonuria starting sapropterin therapy for the purpose of lowering blood phenylalanine levels.
Overall Number of Participants Analyzed 37
Mean (Standard Deviation)
Unit of Measure: grams per day
0.131676  (0.797247)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Subjects With Phenylketonuria Starting Sapropterin Therapy
Comments Objective was to evaluate dietary phenylalanine intake across one year in PKU patients introduced to sapropterin after baseline. Study was prospective cohort in design.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3811
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.131676
Parameter Dispersion
Type: Standard Deviation
Value: 0.797247
Estimation Comments [Not Specified]
8.Other Pre-specified Outcome
Title Change From Baseline in Serotonin at 12 Months
Hide Description Objective: 1 year prospective cohort of PKU patients introduced to sapropterin (Kuvan)to evaluate peripheral neurotransmitter changes across time.
Time Frame Baseline and 12 months
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Subjects With Phenylketonuria Starting Sapropterin Therapy
Hide Arm/Group Description Subjects with Phenylketonuria starting sapropterin therapy for the purpose of lowering blood phenylalanine levels.
All-Cause Mortality
Subjects With Phenylketonuria Starting Sapropterin Therapy
Affected / at Risk (%)
Total   --/--    
Hide Serious Adverse Events
Subjects With Phenylketonuria Starting Sapropterin Therapy
Affected / at Risk (%) # Events
Total   0/58 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Subjects With Phenylketonuria Starting Sapropterin Therapy
Affected / at Risk (%) # Events
Total   20/58 (34.48%)    
Gastrointestinal disorders   
Gastrointestinal upset (not flu) * [1]  3/58 (5.17%)  3
Infections and infestations   
Sinus and general respiratory infections * [2]  11/58 (18.97%)  13
Flu and flu-type sickness * [3]  7/58 (12.07%)  8
Nervous system disorders   
Headache * [4]  8/58 (13.79%)  9
Renal and urinary disorders   
Urinary tract infection * [5]  3/58 (5.17%)  3
Respiratory, thoracic and mediastinal disorders   
Sore throat * [6]  4/58 (6.90%)  6
*
Indicates events were collected by non-systematic assessment
[1]
Diarrhea or acid reflux
[2]
Patients were asked to keep record of illnesses and other adverse events between visits. Patients were encouraged to call in adverse events that occurred between visits but were also queried at each study visit.
[3]
Confirmed and suspected flu as reported by patients
[4]
Headaches or migraines reported by patients
[5]
One UTI case due to congenital kidney deformity which patient had surgically corrected a few weeks later.
[6]
Includes sore throat from strep, flu, cold, or general sore throat.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Rani H. Singh
Organization: Emory University
Phone: 404-448-8519
EMail: rsingh@emory.edu
Layout table for additonal information
Responsible Party: Rani Singh, Emory University
ClinicalTrials.gov Identifier: NCT00688844    
Other Study ID Numbers: IRB00007828
First Submitted: May 29, 2008
First Posted: June 3, 2008
Results First Submitted: August 5, 2013
Results First Posted: August 20, 2014
Last Update Posted: June 8, 2015