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Nicotine Reinforcement and Aversion in Young Adult Light Smokers

Primary Purpose

Nicotine Addiction

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Saline
Nicotine
Sponsored by
Yale University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nicotine Addiction focused on measuring Nicotine, smokers, vitals associated with smoking

Eligibility Criteria

18 Years - 30 Years (Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • Department of Veterans Affairs

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Nicotine

Saline

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

DEQ - Pleasurable
The Drug Effects Questionnaire (DEQ) ratings subscale that measures the pleasurable effects was used. I The minimum score is zero with the maximum score of a 100millimeters. The higher the score means the more pleasurable.
DEQ - Aversive
The DEQ is measured using millimeters. The minimum score is zero with the maximum score of a 100millimeters. rug Effects Questionnaire (DEQ) ratings subscale that measures the aversive effects was used. The higher the score means more aversive.
DEQ - Stimulatory
The Drug Effects Questionnaire (DEQ) ratings subscale that measures the stimulatory effects was used. DEQ is measured using millimeters. The minimum score is zero with the maximum score of a 100millimeters. The higher the score means more stimulation.

Secondary Outcome Measures

Full Information

First Posted
December 7, 2011
Last Updated
August 5, 2021
Sponsor
Yale University
Collaborators
National Institute on Drug Abuse (NIDA)
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1. Study Identification

Unique Protocol Identification Number
NCT01495819
Brief Title
Nicotine Reinforcement and Aversion in Young Adult Light Smokers
Official Title
Nicotine Reinforcement and Aversion in Young Adult Light Smokers
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
January 4, 2017 (Actual)
Primary Completion Date
March 30, 2020 (Actual)
Study Completion Date
March 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Yale University
Collaborators
National Institute on Drug Abuse (NIDA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nicotine Addiction
Keywords
Nicotine, smokers, vitals associated with smoking

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
34 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Nicotine
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Saline
Arm Type
Placebo Comparator
Arm Description
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 Type
Drug
Intervention Name(s)
Saline
Other Intervention Name(s)
Placebo
Intervention Description
5cc's of saline give at least once.
Intervention Type
Drug
Intervention Name(s)
Nicotine
Other Intervention Name(s)
IV nicotine
Intervention Description
(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).
Primary Outcome Measure Information:
Title
DEQ - Pleasurable
Description
The Drug Effects Questionnaire (DEQ) ratings subscale that measures the pleasurable effects was used. I The minimum score is zero with the maximum score of a 100millimeters. The higher the score means the more pleasurable.
Time Frame
Up to 10 Minutes
Title
DEQ - Aversive
Description
The DEQ is measured using millimeters. The minimum score is zero with the maximum score of a 100millimeters. rug Effects Questionnaire (DEQ) ratings subscale that measures the aversive effects was used. The higher the score means more aversive.
Time Frame
Up to 10 Minutes
Title
DEQ - Stimulatory
Description
The Drug Effects Questionnaire (DEQ) ratings subscale that measures the stimulatory effects was used. DEQ is measured using millimeters. The minimum score is zero with the maximum score of a 100millimeters. The higher the score means more stimulation.
Time Frame
Up to10 Minutes

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mehmet Sofuoglu, M.D,Ph.D.
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Veterans Affairs
City
West Haven
State/Province
Connecticut
ZIP/Postal Code
06516
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35254839
Citation
MacLean RR, Eid T, Parida S, Gueorguieva R, DeVito EE, Sofuoglu M. Threshold for the pleasurable effects of nicotine are lower than its reinforcing effects during self-administration. Exp Clin Psychopharmacol. 2023 Feb;31(1):37-45. doi: 10.1037/pha0000556. Epub 2022 Mar 7.
Results Reference
derived

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Nicotine Reinforcement and Aversion in Young Adult Light Smokers

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