Cotinine Metabolism in Infants and Children (1058)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00994591
First received: October 6, 2009
Last updated: May 23, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Secondhand Smoke Exposure
Drug: Pharmacokinetic dosing
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Cotinine Metabolism in Infants and Children

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Cotinine clearance [ Time Frame: 8 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Half-life of cotinine [ Time Frame: 8 hour ] [ Designated as safety issue: No ]

Enrollment: 56
Study Start Date: January 2007
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pharmacokinetic dosing Drug: Pharmacokinetic dosing
Pharmacokinetic testing involves dosing with deuterated cotinine which has an associated IND#61329.

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:

  1. 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
  2. Validate the 3HC/Cot ratio in saliva and in urine as a marker of cotinine clearance and half-life.

    Secondary Specific Aims:

  3. Determine the effects of age on the cotinine metabolite profile in the 8-hour urine sample.
  4. Determine if sulfation is a conjugation pathway for cotinine in infants and young children.
  Eligibility

Ages Eligible for Study:   2 Months to 72 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Ages: 12 months, 13-24 months, and 25-83 months
  • Caucasian (including Hispanic) and African American only
  • Some exposure to secondhand smoke

Exclusion Criteria:

  • Any medical problems
  • Taking prescription medication (there are exceptions)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00994591

Locations
United States, California
University of California, San Francisco, SFGH, CTSI,CRC
San Francisco, California, United States, 94101
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Neal L Benowitz, MD University of California, San Francisco
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00994591     History of Changes
Other Study ID Numbers: 10-03693
Study First Received: October 6, 2009
Last Updated: May 23, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:
Nicotine
Cotinine
CYP2A6

ClinicalTrials.gov processed this record on September 22, 2014