Nicotine's Potential Abuse With Menthol

NCT04535362 | Completed Early Phase 1 Results FDA Drug

• 2 other identifiers: 20000292232U54DA036151-06
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

To examine if switching from menthol to non-menthol cigarettes will change the dose-effect curves for positive subjective effects and alleviation of smoking urges as a function of nicotine delivery rate in smokers.

Conditions

Nicotine Dependence

Outcome Measures

Primary Outcomes (4)

• Drug Effect Questionnaire - Stimulatory Effects

  Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from "not at all" to "extremely.". These ratings were then averaged to create three domain scores reflecting 1) stimulatory effects (average of "feel stimulated", "feel drug effects" and "feel high"), 2) pleasurable effects (average of "like", "feel good " and "want more"), and 3) aversive effects (average of "feel anxious", "feel down" and "feel bad"). Head rush was also assessed. Scores on the subscales range from 0 - 100 where 0 is the measure of least impactful 'effect'.

  Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes

• Drug Effect Questionnaire - Pleasure Effect

  Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from "not at all" to "extremely.". These ratings were then averaged to create three domain scores reflecting: 1) stimulatory effects (average of "feel stimulated", "feel drug effects" and "feel high"), 2) pleasurable effects (average of "like", "feel good " and "want more"), and 3) aversive effects (average of "feel anxious", "feel down" and "feel bad"). Head rush was also assessed. Scores on the subscales range from 0 - 100 where 0 is the measure of least impactful 'effect'.

  Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes

• Drug Effect Questionnaire - Aversive Effect

  Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from "not at all" to "extremely.". These ratings were then averaged to create three domain scores reflecting: 1) stimulatory effects (average of "feel stimulated", "feel drug effects" and "feel high"), 2) pleasurable effects (average of "like", "feel good " and "want more"), and 3) aversive effects (average of "feel anxious", "feel down" and "feel bad"). Head rush was also assessed. Scores on the subscales range from 0 - 100 where 0 is the measure of least impactful 'effect'.

  Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes

• Drug Effect Questionnaire - Head Rush

  Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from "not at all" to "extremely.". These ratings were then averaged to create three domain scores reflecting: 1) stimulatory effects (average of "feel stimulated", "feel drug effects" and "feel high"), 2) pleasurable effects (average of "like", "feel good " and "want more"), and 3) aversive effects (average of "feel anxious", "feel down" and "feel bad"). Head rush was also assessed. Scores on all subscales, including Head Rush scale, range from 0 - 100 where lower scores indicate less head rush.

  Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes

Secondary Outcomes (1)

• SAFTEE

  up to one year

Study Arms (2)

menthol cigarettes

ACTIVE COMPARATOR

Will smoke only menthol cigarettes for two weeks

Drug: Nicotine

non menthol cigarettess

ACTIVE COMPARATOR

Will only smoke non menthol cigarettes for two weeks

Drug: Nicotine

Interventions

Nicotine DRUG

session will include 3 infusions in the same order: nicotine (1 mg per 70 kg body weight) delivered over 5 minutes, saline and nicotine (1 mg/ 70 kg) delivered over 2.5 minutes.

Also known as: intravenous nicotine

menthol cigarettes; non menthol cigarettess

Eligibility Criteria

• Age: 21 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• \) Female and male smokers, aged 21 to 35 years, who have been smoking tobacco cigarettes for at least a year;
• \) smoke ≥ 5 and less than 20 cigarettes per day;
• \) urine cotinine levels \> 100 ng/mL consistent with nicotine intake of an active smoker
• \) not seeking treatment at the time of the study for nicotine dependence;
• \) 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.

You may not qualify if:

• \) history of major medical or psychiatric disorders that the physician investigator deems as contraindicated for the subject to be in the study;
• \) regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics);
• \) current alcohol or substance dependence for any other recreational or prescription drugs other than nicotine;
• \) use of e-cigarettes more than 10 days in the past 30 days;
• \) urine drug screening indicating recent illicit drugs use (with the exception of marijuana).

Sponsors & Collaborators

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

Study Sites (1)

Department of Veterans Affairs Hospital

West Haven, Connecticut, 06516, United States

Location

MeSH Terms

Conditions

Tobacco Use Disorder

Interventions

Nicotine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Mehmet Sofuoglu, MD, PhD: Professor of Psychiatry; Director of VA New England Mental Illness Researc
• Organization: Yale School of Medicine

mehmet.sofuoglu@yale.edu

(203) 937-4809

Study Officials

• Mehmet Sofuoglu, M.D.,Ph.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: The cigarette condition is unblinded but the nicotine infusion is blinded to participant
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Model Details: subjects will be unblinded to smoking menthol or non menthol for two weeks before each test session. Each session will include 3 infusions in the same order: nicotine (1 mg per 70 kg body weight) delivered over 5 minutes, saline and nicotine (1 mg/ 70 kg) delivered over 2.5 minutes. Once the participants complete the test session, participants will be crossed-over to the alternative treatment.

Study Record Dates

• First Submitted: August 24, 2020
• First Posted: September 1, 2020
• Study Start: June 28, 2021
• Primary Completion: June 29, 2023
• Study Completion: June 29, 2023
• Last Updated: August 26, 2024
• Results First Posted: August 26, 2024

Record last verified: 2024-08

Locations

US (1)