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 male and female smokers with or without nicotine dependence (light and intermittent smokers). The investigators propose a double-blind, placebo-controlled study that will enroll 150 individuals with 32 male and 32 female smokers with a total of 64 completers, (16 of each group will be dependent and 16 will be non-dependent). Smokers will participate in four sessions: four test sessions. In each of the four test 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 test session, smokers will sample the assigned nicotine dose and placebo (saline) and then have the opportunity to choose between nicotine and placebo for a total of five choices over a 90-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).
|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 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 six choices.
1.5, 3.0, 4.5, or 6.0 mcg/kg.
Aim #1: To further characterize the reinforcing threshold and dose-response curve for IV nicotine self-administration in male and female smokers with or without nicotine dependence. The reinforcing effects of nicotine will be determined by the number of IV nicotine self-administrations.
Hypothesis 1a) female smokers, compared to males, will have a lower threshold and a steeper slope for nicotine reinforcement, indicating greater sensitivity to nicotine.
Hypothesis 1b) non-dependent smokers, compared to dependent smokers, will have a lower threshold and a steeper slope for nicotine reinforcement.
Aim#2: To further characterize the threshold and dose-response curve for the subjective-rewarding effects of self-administered IV nicotine in male and female smokers with or without nicotine dependence. The subjective-rewarding effects of nicotine will be determined by the "good effects" and "drug liking" items of the Drug Effects Questionnaire.
Hypothesis 2a) female smokers, compared to males, will have a lower threshold and a steeper slope for the subjective-rewarding effects of nicotine.
Hypothesis 2b) non-dependent smokers, compared to dependent smokers, will have a lower threshold and a steeper slope for the subjective-rewarding effects of nicotine, indicating greater sensitivity to nicotine.
|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: Katherine Barrett, B.S., LADC 203-932-5711 ext 5972 Katherine.Barrett@va.gov|
|Principal Investigator: Mehmet Sofuoglu, M.D., Ph.D.|
|Principal Investigator:||Mehmet Sofuoglu, M.D,Ph.D.||Yale University|