NCT03134339

The Effect of Nicotine Delivery Rate on Reinforcement

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: Yale University · Academic / Other
• Sex: All
• Age: 18 Years – 30 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
DRUG	Nicotine saline 0.00mcg/kg/s	saline 0.00mcg/kg/s
DRUG	Nicotine 0.24 mcg/kg/s	nicotine 0.24 mcg/kg/s
DRUG	Nicotine 0.048 mcg/kg/s	nicotine 0.048 mcg/kg/s
DRUG	Nicotine 0.024 mcg/kg/s	nicotine 0.024 mcg/kg/s

Timeline

• Start date: 2017-01-05
• Primary completion: 2018-01-29
• Completion: 2018-01-29
• First posted: 2017-04-28
• Last updated: 2018-10-22

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study