Does Varenicline Influence Alcohol Consumption in Alcohol Dependent Individuals?

NCT00846859 | Completed Phase 2

• 1 other identifier: GOTABU-BO2
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 3

Brief Summary

The aim of the present clinical trial is to investigate whether 14 weeks of treatment with a prescription medication for smoking cessation (European trade name: Champix(R); US trade name: Chantix(R)), can reduce alcohol consumption in alcohol dependent individuals.

Conditions

Alcohol Dependence

Keywords

alcohol dependence; nicotine dependence; alcohol abuse; varenicline; Champix; Chantix; smoking; drinking; snuffing; diary; phosphatidyl ethanol; PEth

Outcome Measures

Primary Outcomes (1)

• Alcohol consumption as measured by diary and questionnaires: the number of heavy drinking days (as percentage) defined as ≥5 standard drinks per day for men and ≥4 standard drinks per day for women

Secondary Outcomes (6)

• Alcohol consumption as measured by diary and questionnaires: total amount (grams) of consumed alcohol compared to baseline.

• Percentage (and number) of abstaining days compared to baseline.

• Drinks per drinking day compared to baseline.

• Alcohol consumption as measured by alcohol markers in blood compared to baseline.

• Nicotine use in alcohol dependent subjects as measured by diary and questionnaires compared to baseline.

Study Arms (2)

varenicline

EXPERIMENTAL

Drug: varenicline (Champix/Chantix)

placebo

PLACEBO COMPARATOR

Drug: placebo for varenicline

Interventions

varenicline (Champix/Chantix) DRUG

14 weeks of per oral tablet treatment in an escalating dosing regimen (0.5 mg - 1.0 mg/day; 1 - 2 tablets/day).

Also known as: Champix(R)/Chantix(R)

varenicline

placebo for varenicline DRUG

14 weeks of per oral tablet treatment in an escalating dosing regimen (1 - 2 tablets/day)

Also known as: placebo for Champix(R) / Chantix(R)

placebo

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 30-70 years at screening
• Alcohol dependence according to DSM-IV (meeting ≥3 out of 7 criteria)
• ≥ 20 heavy drinking days (men: ≥ 5 drinks/day, women: ≥4 drinks/day, where 1 std. drink is defined as 12 g ethanol) during the last 60 days
• Participants must have signed the informed consent

You may not qualify if:

• Subject to treatment of alcohol withdrawal within 30 days of study initiation
• Subject to treatment that may affect alcohol consumption including acamprosate, naltrexone, disulfiram, ondansetron, topiramate, SSRIs, varenicline, mirtazapine, rimonabant, methylphenidate or atomoxetine within 3 months of study initiation
• Subject to treatment of depression within 3 months of study initiation
• The continuous use of drugs such as codeine, hydroxyzine, alimemazine, benzodiazepines or sedatives (the sporadic use of these compounds is accepted)
• Any concurrent medication that may affect the results of the trial or is considered to compromise the safety of the participants in the trial
• History of Delirium Tremens the last 5 years or any history of abstinence-induced seizures
• Laboratory hepatic values of more than 3 times the upper limit of the normal range or other clinically significant abnormalities in the screening laboratory values.
• Participants who are pregnant or nursing infant(s), and women of childbearing potential not using a contraceptive method judged by the investigator to be effective.
• Any ongoing serious psychiatric or somatic disorder
• Any psychiatric Axel I diagnoses (except for nicotine or alcohol dependence)
• The concurrent use of illicit drugs based on urine-toxicity test
• The need for detoxification
• Diabetes Mellitus Type 1
• Suicidal risk
• Homelessness

Sponsors & Collaborators

• Sahlgrenska University Hospital: lead
• Karolinska University Hospital: collaborator
• Malmö University: collaborator

Study Sites (3)

Addiction Biology Unit, Beroendekliniken, University of Gothenburg and Sahlgrenska University Hospital

Gothenburg, 413 45, Sweden

Location

Beroendecentrum, Malmö University Hospital (UMAS), Sweden

Malmo, 205 02, Sweden

Location

Department of Clinical Neuroscience Section of Dependence Research Magnus Huss Clinic: M4:02 Karolinska University Hospital

Stockholm, 171 76, Sweden

Location

Related Publications (23)

• Ericson M, Lof E, Stomberg R, Soderpalm B. The smoking cessation medication varenicline attenuates alcohol and nicotine interactions in the rat mesolimbic dopamine system. J Pharmacol Exp Ther. 2009 Apr;329(1):225-30. doi: 10.1124/jpet.108.147058. Epub 2009 Jan 6.

  PMID: 19126781 BACKGROUND

• Lof E, Olausson P, deBejczy A, Stomberg R, McIntosh JM, Taylor JR, Soderpalm B. Nicotinic acetylcholine receptors in the ventral tegmental area mediate the dopamine activating and reinforcing properties of ethanol cues. Psychopharmacology (Berl). 2007 Dec;195(3):333-43. doi: 10.1007/s00213-007-0899-4. Epub 2007 Aug 17.

  PMID: 17703283 BACKGROUND

• Lof E, Chau PP, Stomberg R, Soderpalm B. Ethanol-induced dopamine elevation in the rat--modulatory effects by subchronic treatment with nicotinic drugs. Eur J Pharmacol. 2007 Jan 26;555(2-3):139-47. doi: 10.1016/j.ejphar.2006.10.056. Epub 2006 Oct 28.

  PMID: 17141214 BACKGROUND

• Soderpalm B, Ericson M, Olausson P, Blomqvist O, Engel JA. Nicotinic mechanisms involved in the dopamine activating and reinforcing properties of ethanol. Behav Brain Res. 2000 Aug;113(1-2):85-96. doi: 10.1016/s0166-4328(00)00203-5.

  PMID: 10942035 BACKGROUND

• Ericson M, Blomqvist O, Engel JA, Soderpalm B. Voluntary ethanol intake in the rat and the associated accumbal dopamine overflow are blocked by ventral tegmental mecamylamine. Eur J Pharmacol. 1998 Oct 9;358(3):189-96. doi: 10.1016/s0014-2999(98)00602-5.

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• Blomqvist O, Ericson M, Engel JA, Soderpalm B. Accumbal dopamine overflow after ethanol: localization of the antagonizing effect of mecamylamine. Eur J Pharmacol. 1997 Sep 10;334(2-3):149-56. doi: 10.1016/s0014-2999(97)01220-x.

  PMID: 9369343 BACKGROUND

• Blomqvist O, Soderpalm B, Engel JA. Ethanol-induced locomotor activity: involvement of central nicotinic acetylcholine receptors? Brain Res Bull. 1992 Aug;29(2):173-8. doi: 10.1016/0361-9230(92)90023-q.

  PMID: 1525672 BACKGROUND

• Blomqvist O, Engel JA, Nissbrandt H, Soderpalm B. The mesolimbic dopamine-activating properties of ethanol are antagonized by mecamylamine. Eur J Pharmacol. 1993 Nov 9;249(2):207-13. doi: 10.1016/0014-2999(93)90434-j.

  PMID: 8287902 BACKGROUND

• Steensland P, Simms JA, Holgate J, Richards JK, Bartlett SE. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking. Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12518-23. doi: 10.1073/pnas.0705368104. Epub 2007 Jul 11.

  PMID: 17626178 BACKGROUND

• Blomqvist O, Hernandez-Avila CA, Van Kirk J, Rose JE, Kranzler HR. Mecamylamine modifies the pharmacokinetics and reinforcing effects of alcohol. Alcohol Clin Exp Res. 2002 Mar;26(3):326-31.

  PMID: 11923584 BACKGROUND

• Young EM, Mahler S, Chi H, de Wit H. Mecamylamine and ethanol preference in healthy volunteers. Alcohol Clin Exp Res. 2005 Jan;29(1):58-65. doi: 10.1097/01.alc.0000150007.34702.16.

  PMID: 15654292 BACKGROUND

• Chi H, de Wit H. Mecamylamine attenuates the subjective stimulant-like effects of alcohol in social drinkers. Alcohol Clin Exp Res. 2003 May;27(5):780-6. doi: 10.1097/01.ALC.0000065435.12068.24.

  PMID: 12766622 BACKGROUND

• Rollema H, Chambers LK, Coe JW, Glowa J, Hurst RS, Lebel LA, Lu Y, Mansbach RS, Mather RJ, Rovetti CC, Sands SB, Schaeffer E, Schulz DW, Tingley FD 3rd, Williams KE. Pharmacological profile of the alpha4beta2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation aid. Neuropharmacology. 2007 Mar;52(3):985-94. doi: 10.1016/j.neuropharm.2006.10.016. Epub 2006 Dec 8.

  PMID: 17157884 BACKGROUND

• Tonstad S. Varenicline for smoking cessation. Expert Rev Neurother. 2007 Feb;7(2):121-7. doi: 10.1586/14737175.7.2.121.

  PMID: 17286546 BACKGROUND

• Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, Billing CB, Gong J, Reeves KR; Varenicline Phase 3 Study Group. Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA. 2006 Jul 5;296(1):56-63. doi: 10.1001/jama.296.1.56.

  PMID: 16820547 BACKGROUND

• Gonzales D, Rennard SI, Jorenby DE, Reeves KR. Comment: Oral varenicline for smoking cessation. Ann Pharmacother. 2007 Apr;41(4):720-1. doi: 10.1345/aph.1H310a. Epub 2007 Mar 20. No abstract available.

  PMID: 17374627 BACKGROUND

• Daeppen JB, Smith TL, Danko GP, Gordon L, Landi NA, Nurnberger JI Jr, Bucholz KK, Raimo E, Schuckit MA. Clinical correlates of cigarette smoking and nicotine dependence in alcohol-dependent men and women. The Collaborative Study Group on the Genetics of Alcoholism. Alcohol Alcohol. 2000 Mar-Apr;35(2):171-5. doi: 10.1093/alcalc/35.2.171.

  PMID: 10787393 BACKGROUND

• Larsson A, Jerlhag E, Svensson L, Soderpalm B, Engel JA. Is an alpha-conotoxin MII-sensitive mechanism involved in the neurochemical, stimulatory, and rewarding effects of ethanol? Alcohol. 2004 Oct-Nov;34(2-3):239-50. doi: 10.1016/j.alcohol.2004.10.002.

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• Larsson A, Svensson L, Soderpalm B, Engel JA. Role of different nicotinic acetylcholine receptors in mediating behavioral and neurochemical effects of ethanol in mice. Alcohol. 2002 Nov;28(3):157-67. doi: 10.1016/s0741-8329(02)00244-6.

  PMID: 12551757 BACKGROUND

• Larsson A, Edstrom L, Svensson L, Soderpalm B, Engel JA. Voluntary ethanol intake increases extracellular acetylcholine levels in the ventral tegmental area in the rat. Alcohol Alcohol. 2005 Sep-Oct;40(5):349-58. doi: 10.1093/alcalc/agh180. Epub 2005 Jul 25.

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MeSH Terms

Conditions

Alcoholism; Tobacco Use Disorder; Smoking

Interventions

Varenicline

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines

Study Officials

• Elin Löf, PhD

  Addiction Biology Unit, University of Gothenburg and Beroendekliniken, Sahlgrenska University Hospital, Sweden

  STUDY DIRECTOR

• Bo Söderpalm, MD, PhD

  Addiction Biology Unit, University of Gothenburg and Beroendekliniken, Sahlgrenska University Hospital, Sweden

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 17, 2009
• First Posted: February 19, 2009
• Study Start: March 1, 2009
• Primary Completion: August 1, 2010
• Study Completion: January 1, 2011
• Last Updated: July 21, 2011

Record last verified: 2011-07

Locations

SE (3)