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Developmental Regulation of Proteins Responsible for Transforming Drugs in the Body

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ClinicalTrials.gov Identifier: NCT00117715
Recruitment Status : Completed
First Posted : July 8, 2005
Results First Posted : August 14, 2017
Last Update Posted : September 12, 2017
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Steve Leeder, Children's Mercy Hospital Kansas City

Study Type Observational
Study Design Observational Model: Case-Only;   Time Perspective: Prospective
Condition Healthy
Intervention Procedure: Genotyping and Phenotyping using dextromethorphan and caffeine as probes
Enrollment 121
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Longitudinal Assessment Cohort
Hide Arm/Group Description Normal healthy children approximately one year of age followed through five years of age to evaluate the ontogeny of CYP1A2, CYP2D6, CYP3A4.
Period Title: Overall Study
Started 121
1 Year 88
1.5 Year 85
2 Year 76
2.5 Year 70
3 Year 61
3.5 Year 60
4 Year 58
4.5 Year 55
5 Year 49
Completed 49
Not Completed 72
Arm/Group Title Longitudinal Assessment Cohort
Hide Arm/Group Description Normal healthy children approximately one year of age followed through five years of age to evaluate the ontogeny of CYP1A2, CYP2D6, CYP3A4.
Overall Number of Baseline Participants 111
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 111 participants
1.21  (0.28)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 111 participants
Female
52
  46.8%
Male
59
  53.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 111 participants
Hispanic or Latino
4
   3.6%
Not Hispanic or Latino
107
  96.4%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 111 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
   0.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
58
  52.3%
White
46
  41.4%
More than one race
6
   5.4%
Unknown or Not Reported
0
   0.0%
1.Primary Outcome
Title Change in CYP2D6 Drug Metabolism Phenotype With Age
Hide Description Concentrations of dextromethorphan(DM) and it's metabolite dextrorphan (DX) are quantified in urine and used to estimate the activity of cytochromes P450 2D6 using the well established DM/DX ratio. The longitudinal study design allows for changes in drug metabolism activity as a function of age which can be characterized via least squares regression where the slope of age vs. DM/DX ratio is examined for deviations from zero.
Time Frame every 6 months for 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants completing each milestone visit at each 0.5 years of age.
Arm/Group Title Longitudinal Assessment Cohort
Hide Arm/Group Description:
Normal healthy children approximately one year of age followed through five years of age to evaluate the ontogeny of CYP1A2, CYP2D6, CYP3A4.
Overall Number of Participants Analyzed 111
Mean (Standard Deviation)
Unit of Measure: unitless ratio
Log (DM/DX) Milestone 1 Number Analyzed 88 participants
-1.974  (0.593)
Log (DM/DX) Milestone 2 Number Analyzed 85 participants
-2.083  (0.617)
Log (DM/DX) Milestone 3 Number Analyzed 76 participants
-2.162  (0.638)
Log (DM/DX) Milestone 4 Number Analyzed 70 participants
-2.073  (0.657)
Log (DM/DX) Milestone 5 Number Analyzed 61 participants
-2.161  (0.669)
Log (DM/DX) Milestone 6 Number Analyzed 60 participants
-2.185  (0.670)
Log (DM/DX) Milestone 7 Number Analyzed 58 participants
-2.284  (0.745)
Log (DM/DX) Milestone 8 Number Analyzed 55 participants
-2.177  (0.699)
Log (DM/DX) Milestone 9 Number Analyzed 49 participants
-2.384  (0.672)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Longitudinal Assessment Cohort
Comments Univariate analysis (ANOVA) of the change in log(DM/DX) over time
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.035
Comments Post-hoc analysis performed using Tukey's Honestly Significant Difference test.
Method ANOVA
Comments [Not Specified]
2.Primary Outcome
Title Change in CYP3A4 Drug Metabolism Phenotype With Age
Hide Description Concentrations of dextromethorphan (DM) metabolites 3-hydroxymorphinan (3HM) and dextrorphan (DX) are quantified in urine and used to estimate the activity of cytochrome P450 3A4 using the well established 3HM/DX ratio. The longitudinal study design allows for changes in drug metabolism activity as a function of age which can be characterized via least squares regression where the slope of age vs. 3HM/DX ratio is examined for deviations from zero.
Time Frame every 6 months for 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants completing each milestone visit at each 0.5 years of age.
Arm/Group Title Longitudinal Assessment Cohort
Hide Arm/Group Description:
Normal healthy children approximately one year of age followed through five years of age to evaluate the ontogeny of CYP1A2, CYP2D6, CYP3A4.
Overall Number of Participants Analyzed 111
Mean (Standard Deviation)
Unit of Measure: unitless ratio
Log (3HM/DX) Milestone 1 Number Analyzed 85 participants
-0.069  (0.180)
Log (3HM/DX) Milestone 2 Number Analyzed 76 participants
-0.117  (0.194)
Log (3HM/DX) Milestone 3 Number Analyzed 71 participants
-0.142  (0.223)
Log (3HM/DX) Milestone 4 Number Analyzed 70 participants
-0.158  (0.276)
Log (3HM/DX) Milestone 5 Number Analyzed 61 participants
-0.109  (0.201)
Log (3HM/DX) Milestone 6 Number Analyzed 60 participants
-0.136  (0.194)
Log (3HM/DX) Milestone 7 Number Analyzed 58 participants
-0.133  (0.164)
Log (3HM/DX) Milestone 8 Number Analyzed 55 participants
-0.122  (0.202)
Log (3HM/DX) Milestone 9 Number Analyzed 49 participants
-0.169  (0.218)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Longitudinal Assessment Cohort
Comments Univariate analysis (ANOVA) of the change in log(3HM/DX) over time
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.194
Comments Post-hoc analysis performed using Tukey's Honestly Significant Difference test.
Method ANOVA
Comments [Not Specified]
3.Primary Outcome
Title Change in CYP1A2 Drug Metabolism Phenotype With Age
Hide Description Concentrations of caffeine metabolites 5-Acetylamino-6-amino-3-methyluracil (AAMU), 1-methylxanthine (1MX), 1-methyluric acid (1MU), and 1,7-dimethyluric acid (17MU) are quantified in urine and used to estimate the activity of cytochrome P450 1A2 using the well established (AAMU+1MX+1MU)/1,7U ratio. The longitudinal study design allows for changes in drug metabolism activity as a function of age which can be characterized via least squares regression where the slope of age vs. (AAMU+1MX+1MU)/1,7U ratio is examined for deviations from zero.
Time Frame every 6 months for 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants completing each milestone visit at each 0.5 years of age.
Arm/Group Title Longitudinal Assessment Cohort
Hide Arm/Group Description:
Normal healthy children approximately one year of age followed through five years of age to evaluate the ontogeny of CYP1A2, CYP2D6, CYP3A4.
Overall Number of Participants Analyzed 111
Mean (Standard Deviation)
Unit of Measure: unitless ratio
Log ((AAMU+1MX+1MU)/1,7U) Milestone 1 Number Analyzed 76 participants
-0.851  (0.185)
Log ((AAMU+1MX+1MU)/1,7U) Milestone 2 Number Analyzed 76 participants
-0.823  (0.170)
Log ((AAMU+1MX+1MU)/1,7U) Milestone 3 Number Analyzed 71 participants
-0.858  (0.204)
Log ((AAMU+1MX+1MU)/1,7U) Milestone 4 Number Analyzed 67 participants
-0.856  (0.150)
Log ((AAMU+1MX+1MU)/1,7U) Milestone 5 Number Analyzed 62 participants
-0.832  (0.168)
Log ((AAMU+1MX+1MU)/1,7U) Milestone 6 Number Analyzed 59 participants
-0.853  (0.169)
Log ((AAMU+1MX+1MU)/1,7U) Milestone 7 Number Analyzed 58 participants
-0.822  (0.142)
Log ((AAMU+1MX+1MU)/1,7U) Milestone 8 Number Analyzed 55 participants
-0.851  (0.170)
Log ((AAMU+1MX+1MU)/1,7U) Milestone 9 Number Analyzed 48 participants
-0.821  (0.167)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Longitudinal Assessment Cohort
Comments Univariate analysis (ANOVA) of the change in log ((AAMU+1MX+1MU)/1,7,U) over time
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.831
Comments Post-hoc analysis performed using Tukey's Honestly Significant Difference test.
Method ANOVA
Comments [Not Specified]
Time Frame 5 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Longitudinal Assessment Cohort
Hide Arm/Group Description Normal healthy children approximately one year of age followed through five years of age to evaluate the ontogeny of CYP1A2, CYP2D6, CYP3A4.
All-Cause Mortality
Longitudinal Assessment Cohort
Affected / at Risk (%)
Total   0/111 (0.00%) 
Hide Serious Adverse Events
Longitudinal Assessment Cohort
Affected / at Risk (%)
Total   0/111 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Longitudinal Assessment Cohort
Affected / at Risk (%)
Total   0/111 (0.00%) 
Not all enrolled participants were available for evaluation at every milestone.
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: J. Steven Leeder
Organization: Children's Mercy Hospital
Phone: 816-234-3059
EMail: sleeder@cmh.edu
Layout table for additonal information
Responsible Party: Steve Leeder, Children's Mercy Hospital Kansas City
ClinicalTrials.gov Identifier: NCT00117715    
Other Study ID Numbers: PPRU 10390
Internal IRB #P00 06-46
First Submitted: July 6, 2005
First Posted: July 8, 2005
Results First Submitted: April 4, 2017
Results First Posted: August 14, 2017
Last Update Posted: September 12, 2017