Pharmacogenetics, Emotional Reactivity and Smoking

NCT00507728 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: 2003-10241R01DA017073NCI-2012-02108
• Study Type: interventional
• Target: 646
• Locations: 1 country
• Sites: 1

Brief Summary

The goals of this placebo-controlled randomized clinical trial were to evaluate the differences in emotional reactivity (peak startle response to affective stimuli) during a cessation attempt among smokers treated with bupropion, varenicline, or placebo, and to determine if these differences were moderated by genotype.

Conditions

Tobacco Use Disorder; Smoking Cessation

Keywords

Pharmacogenetics; Emotional Reactivity; Smoking Cessation Counseling; Smoking; Bupropion; Wellbutrin; Wellbutrin SR; Zyban; Varenicline; Chantix; Placebo

Outcome Measures

Primary Outcomes (2)

• Emotional Reactivity By Pharmacotherapy

  Emotional reactivity measured by the peak eye blink electromyography (EMG) of the orbicularis oculi (ORB) muscle responses to acoustic startle probe delivered during the presentation of emotionally valent stimuli (pleasant, unpleasant, neutral, and smoking-related pictures). A single value was estimated by averaging within the specific time interval.

  Baseline to 1 month

• Emotional Reactivity By Pharmacotherapy Moderated by DRD2 A1 Allele

  The emotional reactivity (ORB EMG) of smokers during cessation will be moderated by genotype. A single value was estimated by averaging within the specific time interval. During a quit attempt, smokers were evaluated on how they react to smoking related cues. An interaction term was then formed by the reactivity to smoking stimulus and genotype.

  Baseline to 1 month

Secondary Outcomes (10)

• Smoking Abstinence at 3 Months

  Baseline to 3 months

• Smoking Abstinence at 3 Months by DRD2 A1 Allele

  Baseline to 3 Month

• Smoking Abstinence at 6 Months

  Abstinence at 6 Months ( the effects shown are the increase/decrease in probability of abstinence for 1 unit increase in the predictor)

• Abstinence at 6 Months by DRD2 A1 Allele

  Baseline to 6 Month ( the effects shown are the increase/decrease in probability of abstinence for 1 unit increase in the predictor)

• Symptoms of Nicotine Withdrawal Using the Wisconsin Smoking Withdrawal Scale (WSWS)

  Baseline to 8 months

Study Arms (3)

Bupropion

EXPERIMENTAL

Bupropion starting dose 150 mg by mouth daily (150 mg every morning for three days; 150 mg twice a day thereafter).

Drug: Bupropion; Behavioral: Smoking Cessation Counseling

Varenicline

EXPERIMENTAL

Varenicline starting dose 0.5 mg by mouth daily (0.5 mg every morning for days 1 - 3, then 0.5 mg twice a day for days 4 - 7, then 1 mg twice a day thereafter).

Drug: Varenicline; Behavioral: Smoking Cessation Counseling

Placebo

PLACEBO COMPARATOR

Placebo by mouth for 12 weeks.

Drug: Placebo; Behavioral: Smoking Cessation Counseling

Interventions

Bupropion DRUG

Starting dose 150 mg by mouth daily (150 mg every morning for three days; 150 mg twice a day thereafter)

Also known as: Wellbutrin, Wellbutrin SR, Zyban

Bupropion

Varenicline DRUG

Starting dose 0.5 mg by mouth daily (0.5 mg every morning for days 1 - 3, then 0.5 mg twice a day for days 4 - 7, then 1 mg twice a day thereafter)

Also known as: Chantix

Varenicline

Placebo DRUG

Placebo by mouth for 12 weeks.

Placebo

Smoking Cessation Counseling BEHAVIORAL

Counseling over 8 months and telephone support calls.

Bupropion; Placebo; Varenicline

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 (CR Clearance \<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, including a past manic or hypomanic episode as well as a lifetime psychotic disorder.
• 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. Women who are two years post menopausal, one year post-tubal ligation, or who have had a partial or full hysterectomy will not be subject to a urine pregnancy test.
• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (16)

• Cui Y, Robinson JD, Versace F, Lam CY, Minnix JA, Karam-Hage M, Dani JA, Kosten TR, Wetter DW, Brown VL, Cinciripini PM. Differential cigarette-related startle cue reactivity among light, moderate, and heavy smokers. Addict Behav. 2012 Aug;37(8):885-9. doi: 10.1016/j.addbeh.2012.02.003. Epub 2012 Feb 15.

  PMID: 22571920 BACKGROUND

• Cui Y, Versace F, Engelmann JM, Minnix JA, Robinson JD, Lam CY, Karam-Hage M, Brown VL, Wetter DW, Dani JA, Kosten TR, Cinciripini PM. Alpha oscillations in response to affective and cigarette-related stimuli in smokers. Nicotine Tob Res. 2013 May;15(5):917-24. doi: 10.1093/ntr/nts209. Epub 2012 Oct 11.

  PMID: 23060019 BACKGROUND

• Cui Y, Robinson JD, Engelmann JM, Lam CY, Minnix JA, Karam-Hage M, Wetter DW, Dani JA, Kosten TR, Cinciripini PM. Reinforcement sensitivity underlying treatment-seeking smokers' affect, smoking reinforcement motives, and affective responses. Psychol Addict Behav. 2015 Jun;29(2):300-311. doi: 10.1037/adb0000050. Epub 2015 Jan 26.

  PMID: 25621416 BACKGROUND

• Cui Y, Engelmann JM, Xian J, Minnix JA, Lam CY, Karam-Hage M, Cinciripini PM, Robinson JD. Pharmacological intervention and abstinence in smokers undergoing cessation treatment: A psychophysiological study. Int J Psychophysiol. 2018 Jan;123:25-34. doi: 10.1016/j.ijpsycho.2017.12.001. Epub 2017 Dec 6.

  PMID: 29223599 BACKGROUND

• Minnix JA, Versace F, Robinson JD, Lam CY, Engelmann JM, Cui Y, Brown VL, Cinciripini PM. The late positive potential (LPP) in response to varying types of emotional and cigarette stimuli in smokers: a content comparison. Int J Psychophysiol. 2013 Jul;89(1):18-25. doi: 10.1016/j.ijpsycho.2013.04.019. Epub 2013 May 2.

  PMID: 23643564 BACKGROUND

• Robinson JD, Versace F, Lam CY, Minnix JA, Engelmann JM, Cui Y, Karam-Hage M, Shete SS, Tomlinson GE, Chen TT, Wetter DW, Green CE, Cinciripini PM. The CHRNA3 rs578776 Variant is Associated with an Intrinsic Reward Sensitivity Deficit in Smokers. Front Psychiatry. 2013 Sep 23;4:114. doi: 10.3389/fpsyt.2013.00114. eCollection 2013.

  PMID: 24065931 BACKGROUND

• Versace F, Minnix JA, Robinson JD, Lam CY, Brown VL, Cinciripini PM. Brain reactivity to emotional, neutral and cigarette-related stimuli in smokers. Addict Biol. 2011 Apr;16(2):296-307. doi: 10.1111/j.1369-1600.2010.00273.x. Epub 2010 Dec 23.

  PMID: 21182573 BACKGROUND

• Versace F, Lam CY, Engelmann JM, Robinson JD, Minnix JA, Brown VL, Cinciripini PM. Beyond cue reactivity: blunted brain responses to pleasant stimuli predict long-term smoking abstinence. Addict Biol. 2012 Nov;17(6):991-1000. doi: 10.1111/j.1369-1600.2011.00372.x. Epub 2011 Oct 4.

  PMID: 21967530 BACKGROUND

• Versace F, Engelmann JM, Robinson JD, Jackson EF, Green CE, Lam CY, Minnix JA, Karam-Hage MA, Brown VL, Wetter DW, Cinciripini PM. Prequit fMRI responses to pleasant cues and cigarette-related cues predict smoking cessation outcome. Nicotine Tob Res. 2014 Jun;16(6):697-708. doi: 10.1093/ntr/ntt214. Epub 2013 Dec 27.

  PMID: 24376278 BACKGROUND

• Meyer MJ, Coull BA, Versace F, Cinciripini P, Morris JS. Bayesian function-on-function regression for multilevel functional data. Biometrics. 2015 Sep;71(3):563-74. doi: 10.1111/biom.12299. Epub 2015 Mar 18.

  PMID: 25787146 BACKGROUND

• Zhu H, Versace F, Cinciripini PM, Rausch P, Morris JS. Robust and Gaussian spatial functional regression models for analysis of event-related potentials. Neuroimage. 2018 Nov 1;181:501-512. doi: 10.1016/j.neuroimage.2018.07.006. Epub 2018 Jul 6.

  PMID: 30057352 BACKGROUND

• Cinciripini PM, Green CE, Robinson JD, Karam-Hage M, Engelmann JM, Minnix JA, Wetter DW, Versace F. Benefits of varenicline vs. bupropion for smoking cessation: a Bayesian analysis of the interaction of reward sensitivity and treatment. Psychopharmacology (Berl). 2017 Jun;234(11):1769-1779. doi: 10.1007/s00213-017-4580-2. Epub 2017 Mar 8.

  PMID: 28275830 BACKGROUND

• Hajizadeh A, Howes S, Theodoulou A, Klemperer E, Hartmann-Boyce J, Livingstone-Banks J, Lindson N. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2023 May 24;5(5):CD000031. doi: 10.1002/14651858.CD000031.pub6.

  PMID: 37230961 DERIVED

• Livingstone-Banks J, Fanshawe TR, Thomas KH, Theodoulou A, Hajizadeh A, Hartman L, Lindson N. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2023 May 5;5(5):CD006103. doi: 10.1002/14651858.CD006103.pub8.

  PMID: 37142273 DERIVED

• Cinciripini PM, Robinson JD, Karam-Hage M, Minnix JA, Lam C, Versace F, Brown VL, Engelmann JM, Wetter DW. Effects of varenicline and bupropion sustained-release use plus intensive smoking cessation counseling on prolonged abstinence from smoking and on depression, negative affect, and other symptoms of nicotine withdrawal. JAMA Psychiatry. 2013 May;70(5):522-33. doi: 10.1001/jamapsychiatry.2013.678.

  PMID: 23536105 DERIVED

• Versace F, Engelmann JM, Jackson EF, Costa VD, Robinson JD, Lam CY, Minnix JA, Brown VL, Wetter DW, Cinciripini PM. Do brain responses to emotional images and cigarette cues differ? An fMRI study in smokers. Eur J Neurosci. 2011 Dec;34(12):2054-63. doi: 10.1111/j.1460-9568.2011.07915.x. Epub 2011 Nov 20.

  PMID: 22097928 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Tobacco Use Disorder; Smoking Cessation; Smoking

Interventions

Bupropion; Varenicline

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Propiophenones; Ketones; Organic Chemicals; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines

Results Point of Contact

• Title: Paul M Cinciripini, MD, Chair, Behavioral Science
• Organization: UT MD Anderson Cancer Center

pcinciri@mdanderson.org

(713) 745-1868

Study Officials

• Paul Cinciripini, PhD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2007
• First Posted: July 26, 2007
• Study Start: December 8, 2005
• Primary Completion: December 18, 2019
• Study Completion: December 18, 2019
• Last Updated: May 6, 2021
• Results First Posted: May 6, 2021

Record last verified: 2021-04

Locations

US (1)