Sensitivity to Intravenous Nicotine: Genetic Moderators

To determine if the mu opioid receptor gene (OPRM1) A118G polymorphism moderates the subjective-rewarding effects of intravenous (IV) nicotine in male and female smokers. The subjective effects of nicotine will be measured with a Drug Effects Questionnaire, including the ratings of "good effects" and "drug liking". We hypothesize that smokers with the AG/GG genotype for the OPRM1 A118G will have attenuated subjective-rewarding effects from IV nicotine when compared to those with AA genotype.

Study Overview

• Status: Completed
• Conditions: Nicotine Dependence
• Intervention / Treatment: Drug: Nicotine; Drug: saline

Detailed Description

Increasing evidence suggest that MOR contribute to nicotine's rewarding effect. Further, the functional OPRM1 A118G variant has been linked to rewarding effects of alcohol in alcohol users and to nicotine in female smokers. Since no previous studies examined the influence of the A118G variation on pure nicotine responses, the next logical step is to evaluate how this genetic polymorphism affects nicotine's rewarding, cognitive, and physiological effects using IV nicotine administration in male and female smokers. In addition, the association of the G398A polymorphism of the CHRNA5 gene (rs16969968) with maximal response to nicotinic agonists justifies examination of this SNP as a moderator of IV nicotine sensitivity in humans (Bierut et al. 2008). This SNP will be examined in an exploratory fashion since it is not feasible to fully stratify the study sample for multiple SNPs. The frequency of rs16969968 SNP ranges from 35%-42% among those of European ancestry, making it feasible to examine this variation in our subject sample.

Currently this study is active and enrollment is continuing. Currently there are 205 completers and on going.(June 2014)

• Study Type: Interventional
• Enrollment (Actual): 213
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • Department of Veterans Affairs

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Female and male smokers, aged 18 to 50 years;
• History of smoking daily for the past 12 months, 10-25 cigarettes daily;
• Not seeking treatment at the time of the study for nicotine dependence;
• Have a FTND score of at least 5 and CO level > 10ppm;
• 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 illnesses that the physician investigator deems as contraindicated for the patient to be in the study;
• Regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics) and recent psychiatric diagnosis and treatment for Axis I disorders including major depression, bipolar affective disorder, schizophrenia or panic disorder;
• Abuse of alcohol or any other recreational or prescription drugs.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Saline; Saline infusion	Drug: saline; intravenous saline
Active Comparator: Nicotine; Intravenous Nicotine	Drug: Nicotine; Intravenous nicotine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
primary hypotheses will test the influence of OPRM1 A118G status on subjective responses to IV nicotine, which will be measured with the drug effects questionnaire (DEQ).	Injections 30 minutes apart

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2009
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: August 31, 2009
• First Submitted That Met QC Criteria: August 31, 2009
• First Posted (Estimate): September 1, 2009

Study Record Updates

• Last Update Posted (Actual): April 19, 2017
• Last Update Submitted That Met QC Criteria: April 17, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: smoking, nicotine, cigarettes
• 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: 0905005103; R03DA027474 (U.S. NIH Grant/Contract); DCNBR / CNB (Other Identifier: NIDA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO