Smoking by IV Pulsed Nicotine

Modeling Tobacco Smoking by IV Pulsed Nicotine in Smokers

To establish a dose-effect curve for nicotine's abuse potential as a function of nicotine dose and delivery rate. Pulsed IV nicotine administration will be used as it closely matches nicotine delivery by inhaled tobacco use.

Study Overview

• Status: Completed
• Conditions: Smoking Cessation
• Intervention / Treatment: Drug: Nicotine 0.2mcg/kg/s and 1.0mcg/kg/s

Detailed Description

Both sub-studies will enroll male and female tobacco cigarette smokers. This study will examine the feasibility of the proposed study parameters in a total of 10 completers. In a crossover design, participants will be tested under 5 conditions: 0.2 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries), 0.2mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries), 1.0 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries) and 1.0 mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries). The main outcome measures will be self-report drug effects and urges to smoke cigarettes.

The investigators hypothesize that the abuse potential and alleviation of smoking urges are produced by nicotine as a function of nicotine dose and delivery rate.

This study is complete with 13 enrolled and 10 completers

• Study Type: Interventional
• Enrollment (Actual): 13
• 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: 18 years to 35 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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
• 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; and 6) 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
• Masking: DOUBLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: nicotine infusion 0.2mg; nicotine infusion 0.2 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries) The day order will be randomized over 5 days.	Drug: Nicotine 0.2mcg/kg/s and 1.0mcg/kg/s; Nicotine infusion 0.2 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries), 0.2mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries), 1.0 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries) and 1.0 mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries).; Other Names: nicotine infusion
EXPERIMENTAL: nicotine infusion 2.0mg; 0.2mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries),	Drug: Nicotine 0.2mcg/kg/s and 1.0mcg/kg/s; Nicotine infusion 0.2 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries), 0.2mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries), 1.0 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries) and 1.0 mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries).; Other Names: nicotine infusion
EXPERIMENTAL: nicotine infusion 1.0mg; 1.0 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries)	Drug: Nicotine 0.2mcg/kg/s and 1.0mcg/kg/s; Nicotine infusion 0.2 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries), 0.2mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries), 1.0 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries) and 1.0 mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries).; Other Names: nicotine infusion
EXPERIMENTAL: nicotine infuison 1.0mg; 1.0 mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries).	Drug: Nicotine 0.2mcg/kg/s and 1.0mcg/kg/s; Nicotine infusion 0.2 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries), 0.2mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries), 1.0 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries) and 1.0 mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries).; Other Names: nicotine infusion
PLACEBO_COMPARATOR: Saline; saline delivered over 2minutes ,2.5minutes,10 minutes	Drug: Nicotine 0.2mcg/kg/s and 1.0mcg/kg/s; Nicotine infusion 0.2 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries), 0.2mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries), 1.0 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries) and 1.0 mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries).; Other Names: nicotine infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate will be used to see the dose effect	the dose-effect curves of nicotine dose and delivery rate in heart rate	During nicotine infusion max of ten minutes

Collaborators and Investigators

• Sponsor: Yale University

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 15, 2019
• Primary Completion (ACTUAL): April 28, 2021
• Study Completion (ACTUAL): May 31, 2021

Study Registration Dates

• First Submitted: July 23, 2020
• First Submitted That Met QC Criteria: July 23, 2020
• First Posted (ACTUAL): July 28, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 20, 2021
• Last Update Submitted That Met QC Criteria: July 13, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• 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: MS059

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