Study of Bupropion Versus Bupropion + Naltrexone for Smoking Cessation

NCT ID: NCT00419731

Last Updated: 2009-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2/PHASE3

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-11-30

Study Completion Date

2010-07-31

Brief Summary

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

Detailed Description

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The purpose of this study is to compare the effects of bupropion + placebo to bupropion + naltrexone as treatments to help smokers quit. Bupropion is an FDA-approved medication for smoking cessation that is believed to provide relief from craving and withdrawal through promotion of two neurotransmitter chemicals, dopamine and noradrenaline. Naltrexone is an FDA-approved medication for the treatment of opiate and alcohol dependence, that appears to function through blocking certain opiate receptors in the brain. It is expected that bupropion + naltrexone will produce higher smoking quit rates than bupropion + placebo. Bupropion alone is effective in alleviating some nicotine withdrawal complaints and craving for nicotine. However, bupropion does not reduce the rewarding effects of slips to smoking. Naltrexone alone is not generally effective as a smoking cessation medication, but it does help to reduce the rewarding effects of slips to smoking. Thus, it may help to prevent full relapse to smoking. In addition, naltrexone can help to reduce craving for cigarettes. It is hypothesized that the differing complementary actions of the two drugs will help smokers more than bupropion alone. In addition to examining smoking quit rates, the proposed study will also look at psychological processes that change during smoking cessation including, nicotine withdrawal, nicotine craving, mood, impulsivity, and attention

Conditions

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Tobacco Use Disorder

Keywords

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nicotine smoking addiction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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1

Bupropion+Placebo

Group Type ACTIVE_COMPARATOR

Bupropion

Intervention Type 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.

2

Bupropion+Naltrexone

Group Type EXPERIMENTAL

Bupropion + Naltrexone

Intervention Type 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.

Interventions

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Bupropion

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.

Intervention Type DRUG

Bupropion + Naltrexone

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 18 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role collaborator

University of Minnesota

OTHER

Sponsor Role lead

Responsible Party

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University of Minnesota

Principal Investigators

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Marc E Mooney, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Univerisity of Minnesota

Locations

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Tobacco Use Research Center, University of Minnesota

Minneapolis, Minnesota, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Marc E Mooney, Ph.D.

Role: CONTACT

Phone: 612-273-9732

Email: [email protected]

Dorothy K Hatsukami, Ph.D.

Role: CONTACT

Phone: 612-626-2121

Email: [email protected]

Facility Contacts

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Marc E Mooney, Ph.D.

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 7665537 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16831112 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12095672 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10663415 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10102765 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10615738 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14750508 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12851023 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14724039 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17008194 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10899371 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10367550 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12810146 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8539322 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9860109 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10234561 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9491065 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 11687036 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17587504 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19364254 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27213949 (View on PubMed)

Other Identifiers

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K01DA019446-01

Identifier Type: NIH

Identifier Source: secondary_id

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DPMC

Identifier Type: OTHER

Identifier Source: secondary_id

K01DA019446-01

Identifier Type: NIH

Identifier Source: org_study_id

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