Intravenous (IV) Nicotine Self Administration: Dose Ranging and Sex Differences in Smokers
The proposed study will examine the threshold for nicotine self-administration using four different nicotine doses in young adult male and female smokers without nicotine dependence (light and intermittent smokers or LITS). We propose a double-blind, placebo-controlled study that will enroll 195 individuals with 36 male and 36 female smokers and a total of 72 completers. Smokers will participate in five Lab sessions: one adaptation and four experimental sessions. In each of the four experimental sessions, smokers will be randomly assigned to one of the four doses of nicotine (1.5, 3.0, 4.5, and 6.0 mcg/kg, or about 0.1, 0.2, 0.3, and 0.4 mg/70 kg). At the beginning of each experimental session, smokers will sample the assigned nicotine dose for that experimental session, and placebo (saline), and then have the opportunity to choose between nicotine and placebo for a total of ten choices over a 180-minute period. The main outcomes will be threshold dose (the minimum dose of nicotine that is self-administered more than placebo) and the slope of dose-response for nicotine self-administration (changes in nicotine self-administration per unit change in nicotine dose). We will also collect measures of nicotine intake (cotinine), nicotine clearance (3-hydroxycotinine (3-HC) / cotinine), and self-report drug effects. Changes in smoking behavior and the use of other tobacco products will be assessed during follow-up visits at 3, 6 and 12 months. Urine cotinine and self-report measures of tobacco use will be collected.
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||IV Nicotine Self Administration: Dose Ranging and Sex Differences in Smokers|
- Blood Pressure [ Time Frame: 4 years to complete ] [ Designated as safety issue: Yes ]a physician will be present and subjects will be attached to a cardiac monitor as well as a blood pressure and heart rate monitoring device. An IV catheter will be in place throughout the session. Subjects will be administered nicotine only if the systolic blood pressure is <150 mmHg and heart rate is <100 beats/minute.
|Study Start Date:||October 2011|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
Active Comparator: Nicotine
subjects will be randomly assigned to one of the four doses of nicotine: 1.5, 3.0, 4.5, or 6.0 mcg/kg. Subjects will first receive saline and the assigned nicotine dose in a randomized order and double-blind fashion. Subjects will be informed that they will be receiving drug A or B, which may be nicotine or saline. This procedure will allow subjects to sample the nicotine and saline that will be available during that session. In addition, subjective and physiological responses to the sample nicotine dose and saline will be assessed.
5cc's of saline give at least once.
Placebo Comparator: Saline
Subjects will have sample A and B, one being nicotine and one being saline. The doses will be blinded from PI, subject and staff. The subject must choose A or B for the next ten choices.
1.5, 3.0, 4.5, or 6.0 mcg/kg.
Aim #1: To characterize the reinforcing threshold and dose-response function for nicotine reinforcement in young adult LITS. Hypothesis #1A: The reinforcing threshold for IV nicotine will range from 1.5 to 6.0 µg/kg. Hypothesis #1B: The dose-response curve for NSA will be increasing steeply above the reinforcement threshold and will be relatively flat in higher doses of nicotine.
Aim #2: To characterize the threshold and dose-response function for the subjective-rewarding effects of nicotine in young adult LITS. This outcome will be determined by the "good effects" and "drug liking" items of the Drug Effects Questionnaire. Hypothesis #2: The threshold for the subjective-reinforcing effects of IV nicotine will range from 1.5 to 6.0 µg/kg.
Aim #1: To examine gender differences for Specific Aims #1 and #2. Aim #2: To explore if higher reinforcement threshold predicts increases in nicotine intake at 3, 6 and 12-month follow-up.
Aim #3: To examine the association between baseline 3-HC / cotinine ratio and nicotine reinforcement threshold.
Aim #4: To compare daily light to intermittent smokers for threshold and dose response-function for nicotine reinforcement.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01495819
|United States, Connecticut|
|Department of Veterans Affairs||Recruiting|
|West Haven, Connecticut, United States, 06516|
|Contact: Lance Barnes 203-937-4823 firstname.lastname@example.org|
|Contact: Marcedes Coffman, M.A. 203-932-5711 ext 4841 email@example.com|
|Principal Investigator: Mehmet Sofuoglu, M.D., Ph.D.|
|Principal Investigator:||Mehmet Sofuoglu, M.D,Ph.D.||Yale University|