HealthyNCT00117715
Developmental Regulation of Proteins Responsible for Transforming Drugs in the Body
An observational study of Healthy, run by Children's Mercy Hospital Kansas City at 1 site in United States.
Trial summary
This is a drug metabolism study in one-year old children involving caffeine and dextromethorphan. Read more about this study
- Who is it for?
- Ages 12 months to 5 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Genotyping and Phenotyping using dextromethorphan and caffeine as probes
- Type of treatment
- Surgery or procedure
- How many people
- 121 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2000to Jan 2010
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 months to 5 years
- All sexes
- Healthy volunteers accepted
- Child
Study population: Healthy children 12 months of age at study entry. Followed longitudinally until 5 uears of age.
Who may be able to join
- Healthy children 12 months of age at enrollment
Who cannot join
- Height and weight ratio outside of the 5th to 100th percentile for adjusted age
- Historical and/or biochemical evidence of hepatic, renal, or hematopoetic dysfunction
- Historical or physical evidence of a neurologic disease/condition (excluding simple, febrile seizures)
- Historical or physical evidence of any disorder associated with swallowing and/or gastrointestinal function
- Concomitant therapy with drugs or other products known to alter the activity of hepatic or intestinal microsomal enzymes(e.g., inducers or inhibitors of CYPs 1A2, 2D6, and/or 3A4), P-glycoprotein or potential competing substrates for the CYPs, under study within 7 days of a scheduled phenotyping evaluation
- Evidence of behavioral, developmental, or psychosocial conditions in the subjects and/or parents/caregivers that, in the opinion of the investigator, would have the potential to adversely impact the level of compliance required for successful study completion
Show all 9Show fewer
- Evidence of geographic instability (i.e., moving of primary residence within last 24 months) that would adversely influence compliance with repeated study visits necessary for completion of the protocol
- Lack of telephone access required to insure adequate subject contact/follow-up
- Inability to obtain written informed consent from the subject's parents/guardians
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Mercy Hospital
Kansas City, Missouri, 64108
About this study
Official title: Developmental Regulation of CYPs 1A2, 2D6, 3A4
This is a drug metabolism study in one-year old children involving caffeine and dextromethorphan.
Read the detailed description
For many years, it has been considered dogma that drug biotransformation capability is limited at best in the fetus and newborn but increases over the first year of life to levels in toddlers and young children that generally exceed adult capacity. There are several situations where examination of clinical PK data has revealed discernable patterns of drug clearance that can be attributed to developmental differences in drug biotransformation. It has become apparent that there are developmental differences in expression among drug metabolizing enzyme families (cytochromes P450 or "CYPs", etc.) Furthermore, individual drug metabolizing enzymes with in a family may have unique developmental profiles that influence the therapeutic response, desired or undesired, to a given agent.
All subjects will have a single 5 ml venous blood sample taken upon admission to the study. All subjects will be given a single oral dose of caffeine and dextromethorphan. Patients will be allowed to consume their normal age appropriate diet around the time of study drug administration and through the sample collection periods. All spontaneously voided urine will be collected for a period of 12 hours following the caffeine and dextromethorphan administration
The specific aim of this proposal is to extend the current longitudinal investigation into the preschool age group (1 to 5 years of age). The developmental profile of CYPs, 1A2, 2D6, and 3A4 will be determined by caffeine and dextromethorphan phenotyping procedures. The purpose of this study is to determine the age/developmental stage at which the CYP2 1A2, 2D6 and 3A4 activities exceed adult activities.
- Conditions
- Healthy
- Being tested
- Genotyping and Phenotyping using dextromethorphan and caffeine as probes
- Keywords
- Developmental regulation of CYPs 1A2, 2D6, 3A4, Ontogeny, pharmacokinetics, drug biotransformation, enzymatic biotransformation of drugs
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genotyping and Phenotyping using dextromethorphan and caffeine as probesProcedure or surgery
Single doses of dextromethorphan (0.3 mg/kg)and caffeine (3.0 mg/kg) are administered and urine is collected overnight for measurement of drug and metabolites to determine drug biotransformation activity.
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in CYP2D6 Drug Metabolism Phenotype With Age
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.
Measured: every 6 months for 5 years
Change in CYP3A4 Drug Metabolism Phenotype With Age
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.
Measured: every 6 months for 5 years
Change in CYP1A2 Drug Metabolism Phenotype With Age
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.
Measured: every 6 months for 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2005 (estimated)
- Study startOct 2000
- Primary completionJan 2010
- Study completionJan 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 121 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Mercy Hospital Kansas City
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Steve Leeder, Children's Mercy Hospital Kansas City
- Investigators
- J. Steven Leeder, Pharm. D, Ph.D., Principal investigator, Children's Mercy Hospital Kansas City
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00117715
- Sponsor's protocol ID
- PPRU 10390
- Other IDs
- Internal IRB #P00 06-46
- Status last verified
- Aug 2017
- First submitted
- 6 Jul 2005
- Last updated
- 12 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Developmental Regulation of CYPs 1A2, 2D6, 3A4
- ClinicalTrials.gov ID
- NCT00117715
- Acronym / sponsor ID
- PPRU 10390
- Conditions
- Healthy
- Keywords
- Developmental regulation of CYPs 1A2, 2D6, 3A4, Ontogeny, pharmacokinetics, drug biotransformation, enzymatic biotransformation of drugs
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 121 participants (actual)
- Lead sponsor
- Children's Mercy Hospital Kansas CityUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Oct 2000
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 8 Jul 2005 (estimated)
- Results
- Posted 14 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a drug metabolism study in one-year old children involving caffeine and dextromethorphan.
Detailed description
For many years, it has been considered dogma that drug biotransformation capability is limited at best in the fetus and newborn but increases over the first year of life to levels in toddlers and young children that generally exceed adult capacity. There are several situations where examination of clinical PK data has revealed discernable patterns of drug clearance that can be attributed to developmental differences in drug biotransformation. It has become apparent that there are developmental differences in expression among drug metabolizing enzyme families (cytochromes P450 or "CYPs", etc.) Furthermore, individual drug metabolizing enzymes with in a family may have unique developmental profiles that influence the therapeutic response, desired or undesired, to a given agent.
All subjects will have a single 5 ml venous blood sample taken upon admission to the study. All subjects will be given a single oral dose of caffeine and dextromethorphan. Patients will be allowed to consume their normal age appropriate diet around the time of study drug administration and through the sample collection periods. All spontaneously voided urine will be collected for a period of 12 hours following the caffeine and dextromethorphan administration
The specific aim of this proposal is to extend the current longitudinal investigation into the preschool age group (1 to 5 years of age). The developmental profile of CYPs, 1A2, 2D6, and 3A4 will be determined by caffeine and dextromethorphan phenotyping procedures. The purpose of this study is to determine the age/developmental stage at which the CYP2 1A2, 2D6 and 3A4 activities exceed adult activities.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 12 months to 5 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- Healthy children 12 months of age at study entry. Followed longitudinally until 5 uears of age.
Key inclusion criteria (1 listed)
- Healthy children 12 months of age at enrollment
Key exclusion criteria (9 listed)
- Height and weight ratio outside of the 5th to 100th percentile for adjusted age
- Historical and/or biochemical evidence of hepatic, renal, or hematopoetic dysfunction
- Historical or physical evidence of a neurologic disease/condition (excluding simple, febrile seizures)
- Historical or physical evidence of any disorder associated with swallowing and/or gastrointestinal function
- Concomitant therapy with drugs or other products known to alter the activity of hepatic or intestinal microsomal enzymes(e.g., inducers or inhibitors of CYPs 1A2, 2D6, and/or 3A4), P-glycoprotein or potential competing substrates for the CYPs, under study within 7 days of a scheduled phenotyping evaluation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Genotyping and Phenotyping using dextromethorphan and caffeine as probesSingle doses of dextromethorphan (0.3 mg/kg)and caffeine (3.0 mg/kg) are administered and urine is collected overnight for measurement of drug and metabolites to determine drug biotransformation activity. | Procedure or surgery | – |
Primary outcome
Change in CYP2D6 Drug Metabolism Phenotype With Age
Time frame: every 6 months for 5 years
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.
Change in CYP3A4 Drug Metabolism Phenotype With Age
Time frame: every 6 months for 5 years
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.
Change in CYP1A2 Drug Metabolism Phenotype With Age
Time frame: every 6 months for 5 years
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
J. Steven Leeder, Pharm. D, Ph.D. principal investigator
Children's Mercy Hospital Kansas City
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Healthy, run by Children's Mercy Hospital Kansas City at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in CYP2D6 Drug Metabolism Phenotype With Age (time frame: every 6 months for 5 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Sep 2017.