Study of Bupropion Versus Bupropion + Naltrexone for Smoking Cessation

NCT00419731 | Unknown Phase 2 DMC

• 2 other identifiers: K01DA019446-01DPMC
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare the effects of bupropion + placebo to bupropion + naltrexone as treatments to help smokers quit.

Conditions

Tobacco Use Disorder

Keywords

nicotine; smoking; addiction

Outcome Measures

Primary Outcomes (5)

• Biochemically-verified point-prevalence abstinence

  7, 11, 16, and 30 weeks post-quit

• Likelihood of progression to a relapse (e.g., return to baseline smoking) following a slip at any time in study.

  At any point following the quit date.

• Treatment completion.

  Weeks 7 and 30.

• Daily cigarette smoking rate.

  Weekly

• Frequency and severity of bupropion and naltrexone side effects.

  Weekly during treatment

Secondary Outcomes (3)

• Attentional bias.

  Weeks 1, 3, and 7.

• Impulsivity.

  Weeks 1, 3, and 7.

• Nicotine withdrawal, craving and negative/positive affect.

  All visits.

Study Arms (2)

1

ACTIVE COMPARATOR

Bupropion+Placebo

Drug: Bupropion

2

EXPERIMENTAL

Bupropion+Naltrexone

Drug: Bupropion + Naltrexone

Interventions

Bupropion DRUG

Sustained-release, 150 mg, q.d., for days 1-3, 150 mg, b.i.d., for balance of 7 weeks. Placebo, 25 mg, q.d., for 7 weeks.

1

Bupropion + Naltrexone DRUG

Bupropion, Sustained-release, 150 mg, q.d., for days 1-3, 150 mg, b.i.d., for balance of 7 weeks. Naltrexone, 25 mg, q.d., for 7 weeks.

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years and older.
• Smoked at least 10 cigarettes/day for at least 1 year.
• English speaking.
• Females who are of childbearing potential must practice effective contraception and meet the following criteria:
• Are instructed to avoid pregnancy through 30 days after the last dose of study medication.
• Have a negative urine pregnancy test at baseline.
• Agree to use of the birth control methods listed: an oral contraceptive agent, an intrauterine device (IUD), an implantable contraceptive (e.g., Norplant), or an injectable contraceptive (e.g., Depo-Provera) for at least one month prior to entering the study and will continue its use through at least 30 days after the last dose of the study medication. A barrier method of contraception (e.g., condom or diaphragm with spermicide) while participating in the study and 30 days after the last dose of study medication.
• Willingness to reduce alcohol consumption during study to 2 or fewer standard drinks/day (3 oz. of alcohol or two beers (12 oz.), or two 5 oz. glasses of wine).
• Willingness to not use illicit drugs during study period including marijuana.

You may not qualify if:

• Concurrent use of tobacco products (other than cigarettes) or nicotine products.
• Contraindications to use of bupropion (i.e., concurrent use of other forms of bupropion, MAO inhibitors, anti-depressant medication, seizure disorder or any clinical situation that might increase risk for seizures, past head injury, current or prior diagnosis of bulimia or anorexia nervosa; bipolar disorder).
• Contraindications to use of naltrexone (i.e., past history of opioid abuse or dependence or evidence of opioid use in the past 30 days; significant hepatocellular injury as evidenced by liver enzyme levels over 3 times normal limits).
• Use of medications whose metabolism or effects may be adversely altered by bupropion or naltrexone. Medications that contraindicate the use of bupropion include theophylline, procarbazine, carbimazole, nialamide, pargyline, toloxatone, iproniazid, and systemic steroids. Medications that contraindicate the use of naltrexone include opioid analgesics and yohimbine.
• Current use of anti-seizure medications, disulfiram, or any medications that significantly challenge liver functioning.
• Treatment for drug or alcohol dependence during the last year, or evidence of alcohol abuse so severe that the patient is judged potentially unable to comply with the protocol.
• Evidence of problem alcohol consumption based on AUDIT.
• Self-reported use of illicit drugs in the past 90 days (including opioids, but excluding marijuana).
• Suicidal or homicidal ideation.
• Current major depression.
• History of bipolar disorder.
• Recent (within twelve months) myocardial infarction.
• Pregnant or lactating or planning pregnancy during treatment period.
• Having plans to leave the immediate geographical area within 9 months.
• Unwillingness or inability to given written informed consent.

Sponsors & Collaborators

• University of Minnesota: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Tobacco Use Research Center, University of Minnesota

Minneapolis, Minnesota, 55414, United States

RECRUITING

Related Publications (21)

• Ascher JA, Cole JO, Colin JN, Feighner JP, Ferris RM, Fibiger HC, Golden RN, Martin P, Potter WZ, Richelson E, et al. Bupropion: a review of its mechanism of antidepressant activity. J Clin Psychiatry. 1995 Sep;56(9):395-401.

  PMID: 7665537 BACKGROUND

• Mooney ME, Sofuoglu M. Bupropion for the treatment of nicotine withdrawal and craving. Expert Rev Neurother. 2006 Jul;6(7):965-81. doi: 10.1586/14737175.6.7.965.

  PMID: 16831112 BACKGROUND

• Lerman C, Roth D, Kaufmann V, Audrain J, Hawk L, Liu A, Niaura R, Epstein L. Mediating mechanisms for the impact of bupropion in smoking cessation treatment. Drug Alcohol Depend. 2002 Jul 1;67(2):219-23. doi: 10.1016/s0376-8716(02)00067-4.

  PMID: 12095672 BACKGROUND

• Shiffman S, Johnston JA, Khayrallah M, Elash CA, Gwaltney CJ, Paty JA, Gnys M, Evoniuk G, DeVeaugh-Geiss J. The effect of bupropion on nicotine craving and withdrawal. Psychopharmacology (Berl). 2000 Jan;148(1):33-40. doi: 10.1007/s002130050022.

  PMID: 10663415 BACKGROUND

• Hutchison KE, Monti PM, Rohsenow DJ, Swift RM, Colby SM, Gnys M, Niaura RS, Sirota AD. Effects of naltrexone with nicotine replacement on smoking cue reactivity: preliminary results. Psychopharmacology (Berl). 1999 Feb;142(2):139-43. doi: 10.1007/s002130050872.

  PMID: 10102765 BACKGROUND

• Wong GY, Wolter TD, Croghan GA, Croghan IT, Offord KP, Hurt RD. A randomized trial of naltrexone for smoking cessation. Addiction. 1999 Aug;94(8):1227-37. doi: 10.1046/j.1360-0443.1999.948122713.x.

  PMID: 10615738 BACKGROUND

• Krishnan-Sarin S, Meandzija B, O'Malley S. Naltrexone and nicotine patch smoking cessation: a preliminary study. Nicotine Tob Res. 2003 Dec;5(6):851-7. doi: 10.1080/14622200310001614601.

  PMID: 14750508 BACKGROUND

• Williams J, Ziedonis DM. Naltrexone-bupropion combination therapy for protracted abstinence dysphoria. Am J Addict. 2003 May-Jun;12(3):270-2. No abstract available.

  PMID: 12851023 BACKGROUND

• Epstein AM, King AC. Naltrexone attenuates acute cigarette smoking behavior. Pharmacol Biochem Behav. 2004 Jan;77(1):29-37. doi: 10.1016/j.pbb.2003.09.017.

  PMID: 14724039 BACKGROUND

• King A, de Wit H, Riley RC, Cao D, Niaura R, Hatsukami D. Efficacy of naltrexone in smoking cessation: a preliminary study and an examination of sex differences. Nicotine Tob Res. 2006 Oct;8(5):671-82. doi: 10.1080/14622200600789767.

  PMID: 17008194 BACKGROUND

• King AC, Meyer PJ. Naltrexone alteration of acute smoking response in nicotine-dependent subjects. Pharmacol Biochem Behav. 2000 Jul;66(3):563-72. doi: 10.1016/s0091-3057(00)00258-6.

  PMID: 10899371 BACKGROUND

• Brauer LH, Behm FM, Westman EC, Patel P, Rose JE. Naltrexone blockade of nicotine effects in cigarette smokers. Psychopharmacology (Berl). 1999 Apr;143(4):339-46. doi: 10.1007/s002130050957.

  PMID: 10367550 BACKGROUND

• Ahmadi J, Ashkani H, Ahmadi M, Ahmadi N. Twenty-four week maintenance treatment of cigarette smoking with nicotine gum, clonidine and naltrexone. J Subst Abuse Treat. 2003 Apr;24(3):251-5. doi: 10.1016/s0740-5472(03)00027-8.

  PMID: 12810146 BACKGROUND

• Sutherland G, Stapleton JA, Russell MA, Feyerabend C. Naltrexone, smoking behaviour and cigarette withdrawal. Psychopharmacology (Berl). 1995 Aug;120(4):418-25. doi: 10.1007/BF02245813.

  PMID: 8539322 BACKGROUND

• Wewers ME, Dhatt R, Tejwani GA. Naltrexone administration affects ad libitum smoking behavior. Psychopharmacology (Berl). 1998 Nov;140(2):185-90. doi: 10.1007/s002130050756.

  PMID: 9860109 BACKGROUND

• Covey LS, Glassman AH, Stetner F. Naltrexone effects on short-term and long-term smoking cessation. J Addict Dis. 1999;18(1):31-40. doi: 10.1300/J069v18n01_04.

  PMID: 10234561 BACKGROUND

• Lerner AG, Oyffe I, Sigal M. Naltrexone-induced reduction of tobacco intake. J Clin Psychiatry. 1998 Jan;59(1):30-1. doi: 10.4088/jcp.v59n0107c. No abstract available.

  PMID: 9491065 BACKGROUND

• David S, Lancaster T, Stead LF. Opioid antagonists for smoking cessation. Cochrane Database Syst Rev. 2001;(3):CD003086. doi: 10.1002/14651858.CD003086.

  PMID: 11687036 BACKGROUND

• Toll BA, Leary V, Wu R, Salovey P, Meandzija B, O'Malley SS. A preliminary investigation of naltrexone augmentation of bupropion to stop smoking with less weight gain. Addict Behav. 2008 Jan;33(1):173-9. doi: 10.1016/j.addbeh.2007.05.012. Epub 2007 Jun 2.

  PMID: 17587504 BACKGROUND

• Plodkowski RA, Nguyen Q, Sundaram U, Nguyen L, Chau DL, St Jeor S. Bupropion and naltrexone: a review of their use individually and in combination for the treatment of obesity. Expert Opin Pharmacother. 2009 Apr;10(6):1069-81. doi: 10.1517/14656560902775750.

  PMID: 19364254 BACKGROUND

• Mooney ME, Schmitz JM, Allen S, Grabowski J, Pentel P, Oliver A, Hatsukami DK. Bupropion and naltrexone for smoking cessation: A double-blind randomized placebo-controlled clinical trial. Clin Pharmacol Ther. 2016 Oct;100(4):344-52. doi: 10.1002/cpt.402. Epub 2016 Jun 20.

  PMID: 27213949 DERIVED

MeSH Terms

Conditions

Tobacco Use Disorder; Smoking; Behavior, Addictive

Interventions

Bupropion; Naltrexone

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Behavior; Compulsive Behavior; Impulsive Behavior

Intervention Hierarchy (Ancestors)

Propiophenones; Ketones; Organic Chemicals; Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Marc E Mooney, Ph.D.

  Univerisity of Minnesota

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marc E Mooney, Ph.D.

CONTACT

612-273-9732; moon0078@umn.edu

Dorothy K Hatsukami, Ph.D.

CONTACT

612-626-2121; hatsu001@umn.edu

Study Design

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

Study Record Dates

• First Submitted: January 8, 2007
• First Posted: January 9, 2007
• Study Start: November 1, 2006
• Primary Completion: February 1, 2010
• Study Completion: July 1, 2010
• Last Updated: December 3, 2009

Record last verified: 2009-12

Locations

US (1)