Effects of Flavors on Nicotine Reinforcement in Smokers

November 18, 2020 updated by: Mehmet Sofuoglu, Yale University
To examine the acute reinforcing effects of menthol, a fruit flavor (green apple) or a fruit flavor plus menthol, alone or in combination with nicotine in smokers. Flavors will be administered by inhalation via electronic cigarettes (e-cigarettes) and nicotine will be administered intravenously. The reinforcing drug effects will be measured with the drug effects questionnaire (DEQ).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a proposed double-blind, crossover study that enrolls young adult smokers who prefer menthol cigarettes. The study will consist of an adaptation session and three test sessions. In the adaptation session, participants will practice using the e-cigarette by sampling the flavors to be used in the test sessions. The test sessions will be performed following overnight abstinence from tobacco. Across the three test sessions, participants will be assigned to a random sequence of the three different e-cigarette conditions: menthol, green apple or menthol plus green apple, a different flavor condition for each test session. In each test session, just after the assigned flavor is delivered via the e-cigarette, participants will receive a random order of one intravenous delivery of saline, and two intravenous deliveries of nicotine (3.6 mcg/kg and 7 mcg/kg or 0.25 mg/70 kg and 0.5 mg/70kg), one hour apart. The test sessions will be performed at least 24 hours apart to minimize carryover nicotine effects. The main outcome measure will be subjective drug effects as measured with the Drug Effects Questionnaire (DEQ). Other outcomes include cardiovascular measures, cognitive performance, and self-report measures of nicotine withdrawal and craving. Cardiovascular measures include heart rate, systolic and diastolic blood pressure. Cognitive performance will be assessed with the Stroop test, mathematical processing test (MPT), and continuous performance test (CPT). Nicotine withdrawal measures will be measured with the Minnesota Nicotine Withdrawal Symptom Checklist (M-NWSC) and the Brief Questionnaire on Smoking Urges (BQSU).

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • West Haven, Connecticut, United States, 06516
        • Veterans Affairs

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 30 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Female and male mentholated cigarette smokers, aged 18 to 30 years; history of smoking for the past 12 months, at least one cigarette per day; smoking status is verified with urinary cotinine levels above 10 ng/ml; not seeking treatment for nicotine dependence at the time of study entry in good health as verified by medical history, screening examination, and screening laboratory tests; for women, not pregnant as determined by pregnancy screening, nor breast feeding, and using acceptable birth control methods.

Exclusion Criteria:

History of major medical illnesses that the physician investigator deems as contraindicated for the patient to be in the study; regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics); psychiatric diagnosis and / or treatment for Axis I disorders including major depression, bipolar affective disorder, schizophrenia or panic disorder in the past month; abuse of alcohol or any other recreational or prescription drugs in the past 30 days; any allergy to propylene glycol or menthol; and 6) aversion to green apple flavor.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: HEALTH_SERVICES_RESEARCH
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: Menthol e-liquid
Menthol Flavor + IV saline Menthol Flavor + IV nicotine (0.25mg/70kg) Menthol Flavor + IV nicotine (0.5mg/70kg)
Drug: IV nicotine
Subjects in each arm will receive three infusions in a random order one hour apart. The infusions will be saline, 0.25mg/70kg and 0.5mg/70kg
Other Names:
  • nicotine, e-liquid
Drug: Menthol flavor
American e-liquids' menthol flavor used in e-cigarettes will be used as the placebo comparator
Other Names:
  • menthol American e-liquids
Drug: green apple
green apple will be added to the menthol flavor
Other Names:
  • green apple American e-liquids
Drug: green apple and menthol
menthol and green apple will be the active intervention
Other Names:
  • green apple and menthol flavor American e-liquids
ACTIVE_COMPARATOR: green apple e-liquid
Green apple + IV saline Green apple + IV nicotine (0.25mg/70kg) Green apple + IV nicotine (0.5mg/70kg)
Drug: IV nicotine
Subjects in each arm will receive three infusions in a random order one hour apart. The infusions will be saline, 0.25mg/70kg and 0.5mg/70kg
Other Names:
  • nicotine, e-liquid
Drug: Menthol flavor
American e-liquids' menthol flavor used in e-cigarettes will be used as the placebo comparator
Other Names:
  • menthol American e-liquids
Drug: green apple
green apple will be added to the menthol flavor
Other Names:
  • green apple American e-liquids
Drug: green apple and menthol
menthol and green apple will be the active intervention
Other Names:
  • green apple and menthol flavor American e-liquids
ACTIVE_COMPARATOR: green apple and menthol e-liquid
Green apple and menthol + IV saline Green apple and menthol + IV nicotine (0.25mg/70kg) Green apple and menthol + IV nicotine (0.5mg/70kg)
Drug: IV nicotine
Subjects in each arm will receive three infusions in a random order one hour apart. The infusions will be saline, 0.25mg/70kg and 0.5mg/70kg
Other Names:
  • nicotine, e-liquid
Drug: Menthol flavor
American e-liquids' menthol flavor used in e-cigarettes will be used as the placebo comparator
Other Names:
  • menthol American e-liquids
Drug: green apple
green apple will be added to the menthol flavor
Other Names:
  • green apple American e-liquids
Drug: green apple and menthol
menthol and green apple will be the active intervention
Other Names:
  • green apple and menthol flavor American e-liquids

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ).
Time Frame: up to 3 hours per test session.

The (DEQ) Drug Effects Questionnaire has eleven questions with a minimum score of 0 to a maximum score of 100.

Peak values from each time points were calculated for the change in the intensity of positive subjective effects as measured with these peak values for like and want more were averaged to obtain a summary score to represent the feel "good drug effects" composite factor. Higher scores for each DEQ represent greater endorsement of that subjective effect (e.g., on the "like drug" scale a response of 90 represents greater liking than a response of 50).
up to 3 hours per test session.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yale University

Collaborators

National Institute on Drug Abuse (NIDA)

Investigators

  • Principal Investigator: Mehmet Sofuoglu, M.D.Ph.D., Yale University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 23, 2018

Primary Completion (ACTUAL)

December 19, 2018

Study Completion (ACTUAL)

January 31, 2019

Study Registration Dates

First Submitted

August 4, 2017

First Submitted That Met QC Criteria

August 8, 2017

First Posted (ACTUAL)

August 9, 2017

Study Record Updates

Last Update Posted (ACTUAL)

December 3, 2020

Last Update Submitted That Met QC Criteria

November 18, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2000021591
  • 1P50DA036151-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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