Pharmacogenetics, Emotional Reactivity and Smoking - Full Text View

Sponsors and Collaborators:	M.D. Anderson Cancer Center National Institutes of Health (NIH)
Information provided by:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00507728

Purpose

Recent advances in smoking cessation have focused on the use of Varenicline and antidepressants (e.g., Bupropion) for the treatment of nicotine dependence. While the efficacy of these treatments has been established in previous studies, researchers know little about how they work. The specific aims of this project are to assess the effects of these drugs on changes in emotional reactivity during cessation, to determine if these effects are moderated by genotype, and to determine whether emotional reactivity predicts time to relapse. A standardized laboratory assessment procedure, known as the acoustic startle probe, will be used to assess emotional reactivity. In this study, 375 smokers will be randomly assigned to receive Bupropion, Varenicline or placebo. Participants will complete three startle assessments consisting of the presentation of an acoustic stimulus (startle probe), immediately preceded by positive, negative or neutral emotional cues or smoking related stimuli. Researchers hypothesize that the emotional reactivity of all smokers during cessation will be significantly less for those treated with either Varenicline or Bupropion in comparison to placebo. It is also hypothesized that emotional reactivity will be lower for those carrying the DRD2 A1 allele and using Varenicline vs. A1 smokers using either Bupropion or placebo. Homozygous A2s are expected to respond similarly to both drugs with higher levels of emotional reactivity being observed for placebo.

Researchers will also characterize other potential markers for neurotransmitter function (DRD4, DAT, SERT, NET) in terms of differences in both baseline emotional reactivity, and response to pharmacotherapy vs. the control. Researchers hope to understand more fully how pharmacotherapies for smoking cessation affect emotional reactivity during cessation (nicotine withdrawal) and what role genetics may play in conferring an advantage to one treatment versus another, through this mechanism.

Condition	Intervention	Phase
Tobacco Use Disorder Smoking Cessation	Drug: Bupropion Drug: Varenicline Drug: Placebo Behavioral: Smoking Cessation Counseling	Phase II Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Pharmacogenetics, Emotional Reactivity and Smoking

Resource links provided by NLM:

MedlinePlus related topics: Quitting Smoking Smoking

Drug Information available for: Bupropion hydrochloride Bupropion Varenicline

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

To learn more about how the drugs Bupropion and Varenicline affect mood and physiological responses in different groups of people as they attempt to quit smoking. [ Time Frame: 5 Years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To learn how these drugs affect responses related to changes in emotion and whether or not a person's genetic make-up makes a difference in how they respond to the medication. [ Time Frame: 5 Years ] [ Designated as safety issue: No ]

Estimated Enrollment:	375
Study Start Date:	December 2005
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Bupropion	Drug: Bupropion 150 mg PO Daily Behavioral: Smoking Cessation Counseling Counseling over 8 months and telephone support calls.
2: Experimental Varenicline	Drug: Varenicline 0.5 mg PO Daily Behavioral: Smoking Cessation Counseling Counseling over 8 months and telephone support calls.
3: Placebo Comparator Placebo	Drug: Placebo Placebo by mouth for 12 weeks. Behavioral: Smoking Cessation Counseling Counseling over 8 months and telephone support calls.

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Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age: 18-65 years old
Smoking: >/= 5 cigarettes per day within the 2 months preceding the screening visit and expired CO greater than or equal to 6 ppm.
Able to follow verbal and written instructions in English and complete all aspects of the study
Have an address and home telephone number where they may be reached
Provide informed consent and agree to all assessments and study procedures
Be the only participant in their household

Exclusion Criteria:

Within the month immediately preceding the screening visit; use of any form of tobacco product other than cigarettes on 3 or more days within a week only if the individual refuses to refrain from non-cigarette tobacco use during the course of this study
Within the month immediately preceding the screening visit; use of marijuana in any form on 3 or more days within a week
Within the two weeks immediately preceding the screening visit, involvement on more than 3 days in any formal smoking cessation activities
Current visual or auditory problems that in the opinion of the investigator would interfere with the completion of study assessments
Treatment on a continuous basis within 2 weeks before the screening visit: any contraindicated medication for Varenicline or Bupropion.
Uncontrolled hypertension or other major contraindications for Bupropion or Varenicline.
Severe renal impairment (<30 ml/min/1.73 m2).
Laboratory evaluations outside normal limits and of potential clinical significance in the opinion of the investigator
Meet current criteria for psychiatric disorders or substance abuse as assessed by the MINI for items A, B, D, I, J, K, L, M and N.
Subject rated as moderate to high on suicidality as assessed by the MINI.
Psychiatric hospitalization within 1 year of screening date.
A positive urine pregnancy test during the screening period.
Pregnant, breast-feeding, or of childbearing potential who is not protected by a medically acceptable, effective method of birth control while enrolled in the study
Use of Varenicline or Bupropion within two weeks before the screening visit.
History of hypersensitivity or allergic reaction to Varenicline, tricyclic antidepressant, Bupropion (Wellbutrin, Zyban) or similar chemical classes or any component of these formulations.
Subject considered by the investigator as unsuitable candidate for receipt of an investigational drug, or unstable to be followed up throughout the entire duration of the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00507728

Contacts

Contact: Paul Cinciripini, PhD

713-792-0919

Locations

United States, Texas
U.T.M.D. Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Paul Cinciripini, PhD

Sponsors and Collaborators

M.D. Anderson Cancer Center

National Institutes of Health (NIH)

Investigators

Principal Investigator:

Paul Cinciripini, PhD

U.T.M.D. Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center Website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	U.T.M.D. Anderson Cancer Center ( Paul Cinciripini, PhD/Professor )
Study ID Numbers:	2003-1024
Study First Received:	July 25, 2007
Last Updated:	April 30, 2009
ClinicalTrials.gov Identifier:	NCT00507728 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

Pharmacogenetics
Emotional Reactivity
Smoking Cessation Counseling
Smoking
Bupropion
Wellbutrin

Wellbutrin SR
Zyban
Varenicline
Chantix
Placebo

Study placed in the following topic categories:

Dopamine Uptake Inhibitors
Neurotransmitter Agents
Tobacco Use Disorder
Psychotropic Drugs
Disorders of Environmental Origin
Varenicline
Smoking

Dopamine
Mental Disorders
Bupropion
Substance-Related Disorders
Dopamine Agents
Antidepressive Agents, Second-Generation
Antidepressive Agents

Additional relevant MeSH terms:

Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Tobacco Use Disorder
Physiological Effects of Drugs
Psychotropic Drugs
Disorders of Environmental Origin
Pharmacologic Actions
Smoking

Habits
Mental Disorders
Therapeutic Uses
Bupropion
Substance-Related Disorders
Dopamine Agents
Antidepressive Agents, Second-Generation
Central Nervous System Agents
Antidepressive Agents

ClinicalTrials.gov processed this record on July 02, 2009