Nicotine Reinforcement and Aversion in Young Adult Light Smokers

NCT01495819 | Completed Early Phase 1 Results DMC FDA Drug

• 2 other identifiers: 10100075141R01DA042528-01
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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

Conditions

Nicotine Addiction

Keywords

Nicotine; smokers; vitals associated with smoking

Outcome Measures

Primary Outcomes (3)

• 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.

  Up to 10 Minutes

• 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.

  Up to 10 Minutes

• 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.

  Up to10 Minutes

Study Arms (2)

Nicotine

ACTIVE COMPARATOR

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.

Drug: Nicotine

Saline

PLACEBO COMPARATOR

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: Saline

Interventions

Saline DRUG

5cc's of saline give at least once.

Also known as: Placebo

Saline

Nicotine DRUG

(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).

Also known as: IV nicotine

Nicotine

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

Sponsors & Collaborators

• Yale University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Department of Veterans Affairs

West Haven, Connecticut, 06516, United States

Location

Related Publications (1)

• 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.

  PMID: 35254839 DERIVED

MeSH Terms

Conditions

Tobacco Use Disorder

Interventions

Sodium Chloride; Nicotine

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Mehmet Sofuoglu, M.D.,Ph.D.
• Organization: Yale University

mehmet.sofuoglu@yale.edu

203-932-5711

Study Officials

• Mehmet Sofuoglu, M.D,Ph.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: December 7, 2011
• First Posted: December 20, 2011
• Study Start: January 4, 2017
• Primary Completion: March 30, 2020
• Study Completion: March 31, 2020
• Last Updated: August 31, 2021
• Results First Posted: August 31, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)