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

This study is currently recruiting participants.
Verified March 2014 by Yale University
Sponsor:
Information provided by (Responsible Party):
Mehmet Sofuoglu, Yale University
ClinicalTrials.gov Identifier:
NCT01495819
First received: December 7, 2011
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention
Nicotine Addiction
Drug: Saline
Drug: Nicotine

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • 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.


Estimated Enrollment: 64
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)
Arms Assigned Interventions
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.
Drug: Saline
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.
Drug: Nicotine
1.5, 3.0, 4.5, or 6.0 mcg/kg.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria: 1) Female and male smokers, aged 18 to 25 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).

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01495819

Locations
United States, Connecticut
Department of Veterans Affairs Recruiting
West Haven, Connecticut, United States, 06516
Contact: Lance Barnes    203-937-4823    lance.barnes@yale.edu   
Contact: Marcedes Coffman, M.A.    203-932-5711 ext 4841    marcedes.coffman@yale.edu   
Principal Investigator: Mehmet Sofuoglu, M.D., Ph.D.         
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Mehmet Sofuoglu, M.D,Ph.D. Yale University
  More Information

No publications provided

Responsible Party: Mehmet Sofuoglu, Principle Investigator, Yale University
ClinicalTrials.gov Identifier: NCT01495819     History of Changes
Other Study ID Numbers: 1010007514
Study First Received: December 7, 2011
Last Updated: March 17, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
Nicotine
smokers
vitals associated with smoking

Additional relevant MeSH terms:
Tobacco Use Disorder
Behavior, Addictive
Substance-Related Disorders
Mental Disorders
Compulsive Behavior
Impulsive Behavior
Nicotine
Nicotine polacrilex
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Central Nervous System Stimulants
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014