The Effect of Nicotine Delivery Rate on Reinforcement

The dose-effect curve to estimate a threshold delivery rate for reinforcement. The project addresses the FDA Center for Tobacco Products (CTP) interest #1: Nicotine dependence threshold among youth and adults and impact of nicotine reduction on tobacco product use behavior (e.g., topography, compensation, switching, multiple use, initiation, cessation and relapse). IV nicotine, in contrast to ECs, can deliver precise, reproducible dosing, which is necessary for accurately assessing dose-response and threshold effects. The estimated threshold for reinforcement will establish a benchmark for evaluating the addictive potential of ECs and other inhaled nicotine products.

Study Overview

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

Detailed Description

A placebo-controlled study that will recruit male and female nicotine dependent smokers/EC users (n=18) to complete four separate experimental sessions. Each session will include one randomly assigned infusion that will be either saline or a single dose of nicotine (1 mg per 70 kg body weight) delivered at three different infusion rates, rapid, moderate or slow (0.24, 0.048 or 0.024 mcg per kg body weight per second). A total infusion duration of 10 min will be maintained during each session by adding saline infusions of variable duration after nicotine delivery. This will be achieved by two separate infusion pumps, one for saline and one for nicotine. For example, the rapid 0.24 mcg/kg/s condition will include a 1 min infusion of nicotine followed by a 9 min infusion of saline. The subjects will be blinded to the infusion pump procedures. The rapid delivery rate, which we have used in our prior studies, induces positive subjective drug effects and suppresses symptoms of nicotine withdrawal. The moderate delivery rate,0.048 mcg/kg/s, approximates the rate of nicotine intake encountered while smoking a typical cigarette over 5 min (4). The slowest nicotine delivery rate, 0.024mcg/kg/s, was chosen to approximate the rate of nicotine intake encountered while using a newer EC (5).

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • VA Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Female and male smokers that smoke ≥ 5 cigarettes per day for the past year
2. aged 18 to 30 years
3. urine cotinine levels > 100 ng/mL consistent with nicotine intake of an active smoker (23)
4. not seeking treatment at the time of the study for nicotine dependence
5. in good health as verified by medical history, screening examination, and screening laboratory tests
6. 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 or psychiatric disorders that the physician investigator deems as contraindicated for the subject to be in the study
2. regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics)
3. current alcohol or substance dependence for any other recreational or prescription drugs other than nicotine
4. urine drug screening indicating recent illicit drugs use (with the exception of marijuana).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Change on items of the Drug Effects Questionnaire (DEQ)	The peak change in the intensity of subjective effects as measured by the DEQ	up to 60 minutes post infusion

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Kevin Jensen, Ph.D., Yale University

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2017
• Primary Completion (Actual): January 29, 2018
• Study Completion (Actual): January 29, 2018

Study Registration Dates

• First Submitted: February 6, 2017
• First Submitted That Met QC Criteria: April 27, 2017
• First Posted (Actual): April 28, 2017

Study Record Updates

• Last Update Posted (Actual): October 22, 2018
• Last Update Submitted That Met QC Criteria: October 19, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: nicotine, smoking
• Additional Relevant MeSH Terms: 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: 1609018390

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
• product manufactured in and exported from the U.S.: No