Study of Bupropion Versus Bupropion + Naltrexone for Smoking Cessation

Tobacco Use Disorder Clinical Trial

Official title:

Phase II Randomized, Double-Blind Trial of Bupropion Versus Bupropion + Naltrexone for Smoking Cessation

Clinical Trial Details — Status: Unknown status

Administrative data

• NCT number: NCT00419731
• Other study ID #: K01DA019446-01
• Secondary ID: K01DA019446-01DP
• Status: Unknown status
• Phase: Phase 2/Phase 3
• First received: January 8, 2007
• Last updated: December 2, 2009
• Start date: November 2006
• Est. completion date: July 2010

Study information

• Verified date: December 2009
• Source: National Institute on Drug Abuse (NIDA)
• Contact: Marc E Mooney, Ph.D.
• Phone: 612-273-9732
• Email: moon0078[@]umn.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Unknown status
• Enrollment: 120
• Est. completion date: July 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Tobacco Use Disorder

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
United States	Tobacco Use Research Center, University of Minnesota	Minneapolis	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
University of Minnesota - Clinical and Translational Science Institute	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

References & Publications (20)

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. — View Citation

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. Review. — View Citation

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. — View Citation

Covey LS, Glassman AH, Stetner F. Naltrexone effects on short-term and long-term smoking cessation. J Addict Dis. 1999;18(1):31-40. — View Citation

David S, Lancaster T, Stead LF. Opioid antagonists for smoking cessation. Cochrane Database Syst Rev. 2001;(3):CD003086. Review. Update in: Cochrane Database Syst Rev. 2006;(4):CD003086. — View Citation

Epstein AM, King AC. Naltrexone attenuates acute cigarette smoking behavior. Pharmacol Biochem Behav. 2004 Jan;77(1):29-37. — View Citation

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. — View Citation

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. — View Citation

King AC, Meyer PJ. Naltrexone alteration of acute smoking response in nicotine-dependent subjects. Pharmacol Biochem Behav. 2000 Jul;66(3):563-72. — View Citation

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. — View Citation

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. — View Citation

Lerner AG, Oyffe I, Sigal M. Naltrexone-induced reduction of tobacco intake. J Clin Psychiatry. 1998 Jan;59(1):30-1. — View Citation

Mooney ME, Sofuoglu M. Bupropion for the treatment of nicotine withdrawal and craving. Expert Rev Neurother. 2006 Jul;6(7):965-81. Review. — View Citation

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 . Review. — View Citation

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. — View Citation

Sutherland G, Stapleton JA, Russell MA, Feyerabend C. Naltrexone, smoking behaviour and cigarette withdrawal. Psychopharmacology (Berl). 1995 Aug;120(4):418-25. — View Citation

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. Epub 2007 Jun 2. — View Citation

Wewers ME, Dhatt R, Tejwani GA. Naltrexone administration affects ad libitum smoking behavior. Psychopharmacology (Berl). 1998 Nov;140(2):185-90. — View Citation

Williams J, Ziedonis DM. Naltrexone-bupropion combination therapy for protracted abstinence dysphoria. Am J Addict. 2003 May-Jun;12(3):270-2. — View Citation

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. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biochemically-verified point-prevalence abstinence		7, 11, 16, and 30 weeks post-quit
Primary	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.
Primary	Treatment completion.		Weeks 7 and 30.
Primary	Daily cigarette smoking rate.		Weekly
Primary	Frequency and severity of bupropion and naltrexone side effects.		Weekly during treatment
Secondary	Attentional bias.		Weeks 1, 3, and 7.
Secondary	Impulsivity.		Weeks 1, 3, and 7.
Secondary	Nicotine withdrawal, craving and negative/positive affect.		All visits.