Nicotine Delivery Rate and Its Abuse Potential: Impact of Menthol

A placebo-controlled study to enroll male and female tobacco smokers who will participate in five experimental sessions. subjects will be given an IV infusion of either saline or 1 mg nicotine at rapid, moderate or slow infusion rates (nicotine at 0.24,0.096, 0.048 and 0.024, mcg per kg body weight per sec).

Study Overview

• Status: Completed
• Conditions: Nicotine Dependence
• Intervention / Treatment: Drug: Nicotine saline infusion 0.00mcg/kg/s; Drug: Nicotine infusion 0.24mcg/kg/s; Drug: Nicotine infusion 0.096mcg/kg/s; Drug: Nicotine infusion 0.048 mcg/kg/s; Drug: Nicotine infusion 0.024mcg/kg/s

Detailed Description

A placebo-controlled study that will enroll male and female tobacco smokers' menthol to participate in five experimental sessions. During the experimental session, subjects will be given an IV infusion of either saline or 1 mg nicotine at rapid, moderate or slow infusion rates (nicotine at 0.24,0.096, 0.048 and 0.024, mcg per kg body weight per sec). The infusion conditions for each experimental session will be determined in random order. Aim 1 is to establish a dose-effect curve for positive subjective effects (drug liking and good drug effects) and alleviation of smoking urges, as a function of nicotine delivery rate in menthol and non-menthol cigarette preferring smokers Aim 2 is to establish a dose-effect curve positive subjective effects and alleviation of smoking urges as a function of nicotine delivery rate. Aim 3 is to establish a dose-effect curve for nicotine's effect to alleviate symptoms of nicotine withdrawal in abstinent smokers as a function of nicotine delivery rate. Aim 4 is to establish a dose-effect curve for nicotine's acute cardiovascular health effects. Data from this project will help to establish benchmark values for nicotine's threshold effects that will guide policies on the nicotine yield of tobacco products. Presented is the time frame at which the peak change was strongest by treatment arm. The possible peak numbers could be 1, 3, 5, 7 and 10 minutes."

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Early Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 33 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Female and male smokers, aged 18 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 (23)
• 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.

Exclusion criteria:

• 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: nicotine saline infusion 0.00mcg/kg/s; 0.00 mcg/kg/s The day order will be randomized per day	Drug: Nicotine saline infusion 0.00mcg/kg/s; saline 0.00mcg/kg/s; Other Names: nicotine infusion
Experimental: nicotine infusion 0.24mcg/kg/s; 0.24mcg/kg/s The day order will be randomized per day	Drug: Nicotine infusion 0.24mcg/kg/s; nicotine 0.24mcg/kg/s; Other Names: nicotine infusion
Experimental: nicotine infusion 0.096mcg/kg/s; 0.096mcg/kg/s The day order will be randomized per day	Drug: Nicotine infusion 0.096mcg/kg/s; nicotine 0.096mcg/kg/s; Other Names: nicotine infusion
Experimental: nicotine infusion 0.048mcg/kg/s; 0.048mcg/kg/s The day order will be randomized per day	Drug: Nicotine infusion 0.048 mcg/kg/s; nicotine 0.048mcg/kg/s; Other Names: nicotine infusion
Experimental: nicotine infusion 0.024mcg/kg/s; 0.048mcg/kg/s The day order will be randomized per day	Drug: Nicotine infusion 0.024mcg/kg/s; nicotine 0.024mcg/kg/s; Other Names: nicotine infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Changes on Items of the Drug Effects Questionnaire (DEQ) - Stimulatory Effects	The peak change in the intensity of subjective effects as measured by the DEQ: Drug stimulatory effects questionnaire; Eleven questions with a minimum score of 0 to a maximum score of 100. Presented is the DEQ score at which the peak change was strongest by treatment arm. Each session took approximately 60 minutes, however the measures were only collected up to 10 minutes post infusion. This correction to the outcome time frame was made when the results were entered. Data were collected at 1, 3, 5, 7 and 10 minute intervals. The outcome measure title DEQ Stimulatory Effects measure was also updated.	up to 10 minutes
Peak Changes on Items of the Drug Effects Questionnaire (DEQ) - Pleasurable Effects	The peak change in the intensity of subjective effects as measured by the DEQ: Drug pleasurable effects questionnaire; Eleven questions with a minimum score of 0 to a maximum score of 100. Presented is the DEQ score at which the peak change was strongest by treatment arm. Each session took approximately 60 minutes, however the measures were only collected up to 10 minutes post infusion. This correction to the outcome time frame was made when the results were entered. Data were collected at 1, 3, 5, 7 and 10 minute intervals. The outcome measure title DEQ Stimulatory Effects measure was also updated.	up to 10 minutes post infusion

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Mehmet Sofuoglu, M.D.,Ph.D., Professor of Psychiatry

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2019
• Primary Completion (Actual): November 19, 2020
• Study Completion (Actual): November 19, 2020

Study Registration Dates

• First Submitted: June 26, 2018
• First Submitted That Met QC Criteria: June 26, 2018
• First Posted (Actual): July 9, 2018

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: 2000023289; R03DA043004-01 (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