Nicotine Reinforcement and Aversion in Young Adult Light Smokers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01495819
Recruitment Status : Recruiting
First Posted : December 20, 2011
Last Update Posted : January 30, 2018
Information provided by (Responsible Party):
Mehmet Sofuoglu, Yale University

December 7, 2011
December 20, 2011
January 30, 2018
January 4, 2017
June 2019   (Final data collection date for primary outcome measure)
DEQ [ Time Frame: 3 years to complete ]
ratings DEQ among smokers
Blood Pressure [ Time Frame: 4 years to complete ]
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.
Complete list of historical versions of study NCT01495819 on Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
Nicotine Reinforcement and Aversion in Young Adult Light Smokers
Nicotine Reinforcement and Aversion in Young Adult Light Smokers
The proposed study will examine the threshold for nicotine self-administration (NSA) using five different nicotine doses in young adult male and female non-dependent smokers (light and intermittent smokers or LITS). We propose a double-blind, placebo-controlled study that will enroll 195 individuals, targeting a total of 72 completers (36 male and 36 females). In each of the five experimental sessions, smokers will be randomly assigned to one of the five doses of nicotine (0.0125, 0.025, 0.05, 0.1 and 0.2 mg/70 kg). The highest dose, 0.2 mg/70 kg, corresponds to nicotine delivered by about one or two puffs of a cigarette. At the beginning of each experimental session, smokers will sample the assigned both the nicotine dose for that experimental session, and the placebo (saline) dose, followed by the opportunity to choose between nicotine and placebo for a total of ten choices over a 150-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

Aim #1: To assess the threshold reinforcing dose and dose-effect curve for IV NSA at low doses in young adult LITS.

Hypothesis #1A: The threshold reinforcing doses for IV NSA will be between 0.0125 to 0.1 mg/70 kg.

Hypothesis #1B: The dose-effect curve for NSA will differ between males and females with relatively flat curve in female smokers.

Aim #2: To assess the threshold and dose-effect curve for the positive and negative/aversive subjective effects of IV nicotine at low doses and its relationship to nicotine reinforcement.

Hypothesis #2 A: The threshold for the positive effects will be between 0.0125 to 0.1 mg/70 kg, for the negative/aversive effect it will be ≥ 0.1 mg/70 kg.

Hypothesis #2B: Nicotine reinforcement will be positively correlated with the positive and negatively correlated with the negative/aversive subjective effects of IV nicotine.

Exploratory Aims: To examine the influence of nicotine clearance rate on nicotine reinforcement threshold and dose-effect curve.

Not Applicable
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Nicotine Addiction
  • Drug: Saline
    5cc's of saline give at least once.
    Other Name: Placebo
  • Drug: Nicotine
    (0.0125, 0.025, 0.0.5, 0.1 and 0.2 mg/70 kg or about 0.18, 0.36, 0.7, 1.4 and 2.8 µg/kg).
    Other Name: IV nicotine
  • Active Comparator: Nicotine
    subjects will be randomly assigned to one of the five doses of nicotine (0.0125, 0.025, 0.0.5, 0.1 and 0.2 mg/70 kg or about 0.18, 0.36, 0.7, 1.4 and 2.8 µg/kg). At the beginning of each experimental session, subjects will first sample the assigned nicotine dose and placebo (saline) condition that are randomly labeled as 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: Nicotine
  • 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: Saline
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
December 2020
June 2019   (Final data collection date for primary outcome measure)

Inclusion criteria: 1) Female and male smokers, aged 18 to30 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; 4) urine cotinine levels >100 ng/mL indicating smoking status and a level <1000 mg/mL consistent with nicotine intake of LITS; 5) not seeking treatment at the time of the study for nicotine dependence; 6) in good health as verified by medical history, screening examination, and screening laboratory tests; 7) 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).

Sexes Eligible for Study: All
18 Years to 30 Years   (Adult)
United States
Not Provided
Plan to Share IPD: Undecided
Mehmet Sofuoglu, Yale University
Yale University
Not Provided
Principal Investigator: Mehmet Sofuoglu, M.D,Ph.D. Yale University
Yale University
January 2018

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