The Effect of Nicotine Delivery Rate on Reinforcement

NCT ID: NCT03134339

Last Updated: 2018-10-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-05
• Study Completion Date: 2018-01-29

Brief Summary

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.

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).

Conditions

Nicotine

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

saline 0.00mcg/kg/s

0.00 mcg/kg/s The day order will be randomized per day

Group Type: EXPERIMENTAL

Nicotine saline 0.00mcg/kg/s

Intervention Type: DRUG

saline 0.00mcg/kg/s

0.24mcg/kg/s

0.24 mcg/kg/s The day order will be randomized per day

Group Type: EXPERIMENTAL

Nicotine 0.24 mcg/kg/s

Intervention Type: DRUG

nicotine 0.24 mcg/kg/s

0.048mcg/kg/s

0.048 mcg/kg/s The day order will be randomized per day

Group Type: EXPERIMENTAL

Nicotine 0.048 mcg/kg/s

Intervention Type: DRUG

nicotine 0.048 mcg/kg/s

0.024 mcg/kg/s

0.024 mcg/kg/s The day order will be randomized per day

Group Type: EXPERIMENTAL

Nicotine 0.024 mcg/kg/s

Intervention Type: DRUG

nicotine 0.024 mcg/kg/s

Interventions

Nicotine saline 0.00mcg/kg/s

saline 0.00mcg/kg/s

Intervention Type: DRUG

Nicotine 0.24 mcg/kg/s

nicotine 0.24 mcg/kg/s

Intervention Type: DRUG

Nicotine 0.048 mcg/kg/s

nicotine 0.048 mcg/kg/s

Intervention Type: DRUG

Nicotine 0.024 mcg/kg/s

nicotine 0.024 mcg/kg/s

Intervention Type: DRUG

Other Intervention Names

nicotine infusion; nicotine infusion; nicotine infusion; nicotine infusion

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Mehmet Sofuoglu

The effect of nicotine delivery rate on reinforcement

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kevin Jensen, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Yale University

Mehmet Sofuoglu, M.D.,Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

VA Hospital

West Haven, Connecticut, United States

Countries

United States

Other Identifiers

1609018390

Identifier Type: -

Identifier Source: org_study_id