Secondhand Smoke ExposurePhase 11058NCT00994591
Cotinine Metabolism in Infants and Children
A Phase 1 study testing Pharmacokinetic dosing in people with Secondhand Smoke Exposure, run by University of California, San Francisco at 1 site in United States.
Trial summary
Levels of cotinine, a biomarker for nicotine, have been found to be higher in infants and small children than adults. This pharmacokinetic study is designed to determine whether children metabolize cotinine differently than adults. Read more about this study
- Who is it for?
- Ages 2 to 72 monthsHealthy volunteers can take part
- Conditions the study is for
- Secondhand Smoke Exposure
- What is being tested?
- Pharmacokinetic dosing
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2007to Jun 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 2 to 72 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Ages: 12 months, 13-24 months, and 25-83 months
- Caucasian (including Hispanic) and African American only
- Some exposure to secondhand smoke
Who cannot join
- Any medical problems
- Taking prescription medication (there are exceptions)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco, SFGH, CTSI,CRC
San Francisco, California, 94101
About this study
Levels of cotinine, a biomarker for nicotine, have been found to be higher in infants and small children than adults. This pharmacokinetic study is designed to determine whether children metabolize cotinine differently than adults.
Seventy-two healthy children between the ages of 2 months and 6 years will come with their mothers to SFGH GCRC for one approximately 9 hour visit. After being examined by a pediatrician, the child will be administered one dose of cotinine at .05 mg/kg.
Read more
Saliva and urine samples will be collected prior to dosing and throughout the day to characterize the metabolism and excretion of cotinine. The investigators have previously shown that a ratio of 3'-hydroxycotinine/cotinine (3HC/Cot) in saliva correlates closely to nicotine metabolism.
Following these one day hospital visits, a research assistant will visit the participants in their homes to collect urine and saliva samples at 1,2,3,7, and 10 days after the initial dose.
Read the detailed description
The long-term goal is to characterize developmental changes in CYP2A6 activity and nicotine and cotinine metabolism in infants and children. Our hypotheses are:
- The rate of nicotine and cotinine metabolism and the level of CYP2A6 activity will increase with age throughout infancy and childhood.
- The rate of cotinine glucuronidation (reflecting UGT 1A4 and 1A9 activity) will increase with age.
- Cotinine clearance will be lower and cotinine half-life longer in African-Americans compared to Caucasians.
- The excretion of cotinine glucuronide will be less among African-Americans compared to Caucasians.
- Developmental increases in CYP2A6 will be greatest in children with wild type CYP2A6 genes, and will be lower in children who have CYP2A6 gene variants associated with reduced activity.
This present study is the first step in the investigation of the above hypotheses. The primary goal of this study is to determine if there are age-related changes in cotinine clearance and validate the 3HC/COT ratio as a biomarker of cotinine clearance and half-life. This biomarker can then be used in larger studies to explore the hypotheses described above. The biomarker could also be used in epidemiologic studies of the health effects of SHS in infants and children.
Primary Specific Aims:
- Determine the following in infants and children between 2 and 84 months of age dosed with deuterium-labeled cotinine:
- The clearance of cotinine
- The half-life of cotinine
- The volume of distribution of cotinine
- Validate the 3HC/Cot ratio in saliva and in urine as a marker of cotinine clearance and half-life. Secondary Specific Aims:
- Determine the effects of age on the cotinine metabolite profile in the 8-hour urine sample.
- Determine if sulfation is a conjugation pathway for cotinine in infants and young children.
- Conditions
- Secondhand Smoke Exposure
- Being tested
- Pharmacokinetic dosing
- Keywords
- Nicotine, Cotinine, CYP2A6
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pharmacokinetic dosingDrug
Pharmacokinetic testing involves dosing with deuterated cotinine which has an associated IND#61329.
| Study group | Role | What they receive |
|---|---|---|
| Pharmacokinetic dosing | Experimental | Not described Receives: Drug: Pharmacokinetic dosing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cotinine clearance
Measured: 8 hours
Secondary outcomes (1)
Half-life of cotinine
Measured: 8 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2009 (estimated)
- Study startJan 2007
- Primary completionJun 2011
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Secondhand Smoke ExposureStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Neal L Benowitz, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00994591
- Sponsor's protocol ID
- 10-03693
- Acronym
- 1058
- Status last verified
- May 2013
- First submitted
- 6 Oct 2009
- Last updated
- 24 May 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cotinine Metabolism in Infants and Children
- ClinicalTrials.gov ID
- NCT00994591
- Acronym / sponsor ID
- 1058 / 10-03693
- Conditions
- Secondhand Smoke Exposure
- Keywords
- Nicotine, Cotinine, CYP2A6
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- Jan 2007
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 14 Oct 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Levels of cotinine, a biomarker for nicotine, have been found to be higher in infants and small children than adults. This pharmacokinetic study is designed to determine whether children metabolize cotinine differently than adults.
Seventy-two healthy children between the ages of 2 months and 6 years will come with their mothers to SFGH GCRC for one approximately 9 hour visit. After being examined by a pediatrician, the child will be administered one dose of cotinine at .05 mg/kg.
Saliva and urine samples will be collected prior to dosing and throughout the day to characterize the metabolism and excretion of cotinine. The investigators have previously shown that a ratio of 3'-hydroxycotinine/cotinine (3HC/Cot) in saliva correlates closely to nicotine metabolism.
Following these one day hospital visits, a research assistant will visit the participants in their homes to collect urine and saliva samples at 1,2,3,7, and 10 days after the initial dose.
Detailed description
The long-term goal is to characterize developmental changes in CYP2A6 activity and nicotine and cotinine metabolism in infants and children. Our hypotheses are:
- The rate of nicotine and cotinine metabolism and the level of CYP2A6 activity will increase with age throughout infancy and childhood.
- The rate of cotinine glucuronidation (reflecting UGT 1A4 and 1A9 activity) will increase with age.
- Cotinine clearance will be lower and cotinine half-life longer in African-Americans compared to Caucasians.
- The excretion of cotinine glucuronide will be less among African-Americans compared to Caucasians.
- Developmental increases in CYP2A6 will be greatest in children with wild type CYP2A6 genes, and will be lower in children who have CYP2A6 gene variants associated with reduced activity.
This present study is the first step in the investigation of the above hypotheses. The primary goal of this study is to determine if there are age-related changes in cotinine clearance and validate the 3HC/COT ratio as a biomarker of cotinine clearance and half-life. This biomarker can then be used in larger studies to explore the hypotheses described above. The biomarker could also be used in epidemiologic studies of the health effects of SHS in infants and children.
Primary Specific Aims:
- Determine the following in infants and children between 2 and 84 months of age dosed with deuterium-labeled cotinine:
- The clearance of cotinine
- The half-life of cotinine
- The volume of distribution of cotinine
- Validate the 3HC/Cot ratio in saliva and in urine as a marker of cotinine clearance and half-life. Secondary Specific Aims:
- Determine the effects of age on the cotinine metabolite profile in the 8-hour urine sample.
- Determine if sulfation is a conjugation pathway for cotinine in infants and young children.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pharmacokinetic dosing | Experimental | Drug: Pharmacokinetic dosing |
Who may qualify
- Ages
- 2 to 72 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Ages: 12 months, 13-24 months, and 25-83 months
- Caucasian (including Hispanic) and African American only
- Some exposure to secondhand smoke
Key exclusion criteria (2 listed)
- Any medical problems
- Taking prescription medication (there are exceptions)
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 |
|---|---|---|
| Pharmacokinetic dosingPharmacokinetic testing involves dosing with deuterated cotinine which has an associated IND#61329. | Drug | Pharmacokinetic dosing |
Primary outcome
Cotinine clearance
Time frame: 8 hours
1 secondary outcome
Half-life of cotinine
Time frame: 8 hour
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2013.
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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.
Neal L Benowitz, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pharmacokinetic dosing in people with Secondhand Smoke Exposure, run by University of California, San Francisco 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 3 inclusion and 2 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 24 May 2013. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Cotinine clearance (time frame: 8 hours). 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 24 May 2013.