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Sensitivity to Intravenous Nicotine: Genetic Moderators

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00969137
Recruitment Status : Completed
First Posted : September 1, 2009
Last Update Posted : April 19, 2017
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Mehmet Sofuoglu, Yale University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Nicotine Dependence Drug: saline Drug: Nicotine Phase 1

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)

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 213 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Health Services Research
Official Title: Sensitivity to Intravenous Nicotine: Genetic Moderators
Actual Study Start Date : June 2, 2009
Actual Primary Completion Date : June 1, 2016
Actual Study Completion Date : June 1, 2016

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Nicotine
Intravenous Nicotine
Drug: Nicotine
Intravenous nicotine

Placebo Comparator: Saline
Saline infusion
Drug: saline
intravenous saline

Primary Outcome Measures :
  1. 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). [ Time Frame: Injections 30 minutes apart ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00969137

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United States, Connecticut
Department of Veterans Affairs
West Haven, Connecticut, United States, 06516
Sponsors and Collaborators
Yale University
National Institute on Drug Abuse (NIDA)
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Principal Investigator: Mehmet Sofuoglu, M.D,Ph.D. Yale University

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Responsible Party: Mehmet Sofuoglu, Principle Investigator, Yale University Identifier: NCT00969137     History of Changes
Other Study ID Numbers: 0905005103
R03DA027474 ( U.S. NIH Grant/Contract )
DCNBR / CNB ( Other Identifier: NIDA )
First Posted: September 1, 2009    Key Record Dates
Last Update Posted: April 19, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Mehmet Sofuoglu, Yale University:
smoking, nicotine, cigarettes
Additional relevant MeSH terms:
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Tobacco Use Disorder
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action