Cotinine Metabolism in Infants and Children

Secondhand Smoke Exposure Clinical Trial

— 1058  

Official title:

Cotinine Metabolism in Infants and Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00994591
• Other study ID #: 10-03693
• Status: Completed
• Phase: Phase 1
• First received: October 6, 2009
• Last updated: May 23, 2013
• Start date: January 2007
• Est. completion date: June 2011

Study information

• Verified date: May 2013
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 2 Months to 72 Months

Eligibility

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)

Study Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Secondhand Smoke Exposure

Intervention

Drug:
• Pharmacokinetic dosing
Pharmacokinetic testing involves dosing with deuterated cotinine which has an associated IND#61329.

Locations

Country	Name	City	State
United States	University of California, San Francisco, SFGH, CTSI,CRC	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cotinine clearance		8 hours	No
Secondary	Half-life of cotinine		8 hour	No