Intravenous (IV) Nicotine Self Administration: Dose Ranging and Sex Differences in Smokers

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2016 by Yale University
Information provided by (Responsible Party):
Mehmet Sofuoglu, Yale University Identifier:
First received: December 7, 2011
Last updated: January 8, 2016
Last verified: January 2016

December 7, 2011
January 8, 2016
October 2011
May 2016   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01495819 on Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
Intravenous (IV) Nicotine Self Administration: Dose Ranging and Sex Differences in Smokers
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.

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.

Not Provided
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Nicotine Addiction
  • Drug: Saline
    5cc's of saline give at least once.
  • Drug: Nicotine
    1.5, 3.0, 4.5, or 6.0 mcg/kg.
  • 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.
    Intervention: Drug: Saline
  • 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.
    Intervention: Drug: Nicotine
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
December 2016
May 2016   (final data collection date for primary outcome measure)

Inclusion criteria: 1) Female and male smokers, aged 18 to 50 years, who have been smoking for at least a year, and a life-time consumption of at least 100 cigarettes; 2) smoke more frequently than once a week and ≤5 cpd; 3) FTND score <3 indicating no or minimal evidence for nicotine dependence and not meeting DSM-IV criteria for nicotine dependence;3) ; 4) not seeking treatment at the time of the study for nicotine dependence; 5) in good health as verified by medical history, screening examination, and screening laboratory tests; 6) for women, not pregnant as determined by pregnancy screening, nor breast feeding, and using acceptable birth control methods.

Exclusion criteria: 1) history of major medical illnesses that the physician investigator deems as contraindicated for the subject to be in the study; 2) requirement of any form of regular psychotropic medication (antidepressants, antipsychotics, or anxiolytics) or psychiatric diagnosis and treatment for psychiatric disorders including major depression, bipolar disorder, schizophrenia in the past 6 months; and 3) current dependence to alcohol or any other recreational or prescription drugs and; 4) daily use of smokeless tobacco products or exclusive daily use of e-cigarettes (non-daily users will be included).

18 Years to 25 Years
United States
Not Provided
Not Provided
Mehmet Sofuoglu, Yale University
Yale University
Not Provided
Principal Investigator: Mehmet Sofuoglu, M.D,Ph.D. Yale University
Yale University
January 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP