Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Sensitivity to Intravenous Nicotine: Genetic Moderators

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by Yale University
Sponsor:
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Mehmet Sofuoglu, Yale University
ClinicalTrials.gov Identifier:
NCT00969137
First received: August 31, 2009
Last updated: July 18, 2016
Last verified: July 2016
  Purpose
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 Intervention Phase
Nicotine Dependence
Drug: saline
Drug: Nicotine
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Health Services Research
Official Title: Sensitivity to Intravenous Nicotine: Genetic Moderators

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 300
Study Start Date: June 2009
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Nicotine
Intravenous Nicotine
Drug: Nicotine
Intravenous nicotine
Placebo Comparator: Saline
Saline infusion
Drug: saline
intravenous 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)

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00969137

Contacts
Contact: Lance Barnes 203-937-4823 lance.barnes@yale.edu
Contact: Stacy Minnix, BSW 203-937-4805 stacy.minnix@yale.edu

Locations
United States, Connecticut
Department of Veterans Affairs Recruiting
West Haven, Connecticut, United States, 06516
Contact: Mehmet Sofuoglu, M.D., Ph.D.    203-937-4809    mehmet.sofuoglu@yale.edu   
Contact: Joel Gelernter, M.D.    932-5711 ext 3590    joel.gelernter@yale.edu   
Principal Investigator: Mehmet Sofuoglu, M.D., Ph.D.         
Sponsors and Collaborators
Yale University
National Institute on Drug Abuse (NIDA)
Investigators
Principal Investigator: Mehmet Sofuoglu, M.D,Ph.D. Yale University
  More Information

Responsible Party: Mehmet Sofuoglu, Principle Investigator, Yale University
ClinicalTrials.gov Identifier: NCT00969137     History of Changes
Other Study ID Numbers: 0905005103  R03DA027474  DCNBR / CNB 
Study First Received: August 31, 2009
Last Updated: July 18, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Yale University:
smoking, nicotine, cigarettes

Additional relevant MeSH terms:
Tobacco Use Disorder
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Nicotine
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

ClinicalTrials.gov processed this record on September 28, 2016