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Does Varenicline Influence Alcohol Consumption in Alcohol Dependent Individuals?
This study is currently recruiting participants.
Verified by Sahlgrenska University Hospital, Sweden, March 2009
First Received: February 17, 2009   Last Updated: March 18, 2009   History of Changes
Sponsors and Collaborators: Sahlgrenska University Hospital, Sweden
Karolinska University Hospital
Malmö University Hospital, Sweden
Information provided by: Sahlgrenska University Hospital, Sweden
ClinicalTrials.gov Identifier: NCT00846859
  Purpose

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


Condition Intervention Phase
Alcohol Dependence
Drug: varenicline
Drug: placebo for varenicline
Phase II

MedlinePlus related topics: Alcohol Alcoholism Smoking
Drug Information available for: Ethanol Varenicline
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Official Title: Does Varenicline Influence Alcohol Consumption in Alcohol Dependent Individuals?

Further study details as provided by Sahlgrenska University Hospital, Sweden:

Primary Outcome Measures:
  • 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 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Alcohol consumption as measured by diary and questionnaires: total amount (grams) of consumed alcohol compared to baseline. [ Designated as safety issue: No ]
  • Percentage (and number) of abstaining days compared to baseline. [ Designated as safety issue: No ]
  • Drinks per drinking day compared to baseline. [ Designated as safety issue: No ]
  • Alcohol consumption as measured by alcohol markers in blood compared to baseline. [ Designated as safety issue: No ]
  • Nicotine use in alcohol dependent subjects as measured by diary and questionnaires compared to baseline. [ Designated as safety issue: No ]
  • Compliance as measured by diary and returned medication packages. [ Designated as safety issue: No ]

Estimated Enrollment: 162
Study Start Date: March 2009
Estimated Study Completion Date: July 2011
Estimated Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
varenicline: Experimental Drug: varenicline
14 weeks of per oral tablet treatment in an escalating dosing regimen (0.5 mg - 1.0 mg/day; 1 - 2 tablets/day).
placebo: Placebo Comparator Drug: placebo for varenicline
14 weeks of per oral tablet treatment in an escalating dosing regimen (1 - 2 tablets/day)

  Eligibility

Ages Eligible for Study:   30 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age: 30-70 years at screening
  2. Alcohol dependence according to DSM-IV (meeting ≥3 out of 7 criteria)
  3. ≥ 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
  4. Participants must have signed the informed consent

Exclusion Criteria:

  1. Subject to treatment of alcohol withdrawal within 30 days of study initiation
  2. 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
  3. Subject to treatment of depression within 3 months of study initiation
  4. The continuous use of drugs such as codeine, hydroxyzine, alimemazine, benzodiazepines or sedatives (the sporadic use of these compounds is accepted)
  5. Any concurrent medication that may affect the results of the trial or is considered to compromise the safety of the participants in the trial
  6. History of Delirium Tremens the last 5 years or any history of abstinence-induced seizures
  7. 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.
  8. 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.
  9. Any ongoing serious psychiatric or somatic disorder
  10. Any psychiatric Axel I diagnoses (except for nicotine or alcohol dependence)
  11. The concurrent use of illicit drugs based on urine-toxicity test
  12. The need for detoxification
  13. Diabetes Mellitus Type 1
  14. Suicidal risk
  15. Homelessness
  16. Additional factors that implies to the investigator/physician that the participant will not be completing the study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00846859

Contacts
Contact: Elin Löf, PhD +46-31-342 ext 4223 elin.lof@neuro.gu.se
Contact: Andrea deBejczy, MD +46-31+342 ext 2160 andrea.deBejczy@neuro.gu.se

Locations
Sweden
Addiction Biology Unit, Beroendekliniken, University of Gothenburg and Sahlgrenska University Hospital Recruiting
Gothenburg, Sweden, 413 45
Contact: Elin Löf, PhD         elin.lof@neuro.gu.se    
Sub-Investigator: Elin Löf, PhD            
Sub-Investigator: Andrea deBejczy, MD            
Principal Investigator: Bo Söderpalm, MD, PhD            
Department of Clinical Neuroscience Section of Dependence Research Magnus Huss Clinic: M4:02 Karolinska University Hospital Not yet recruiting
Stockholm, Sweden, 171 76
Contact: Anders Hammarberg         anders.hammarberg@ki.se    
Sub-Investigator: Anders Hammarberg            
Principal Investigator: Johan Franck, MD, PhD            
Beroendecentrum, Malmö University Hospital (UMAS), Sweden Not yet recruiting
Malmö, Sweden, 205 02
Contact: Therése Grahn         therese.grahn@skane.se    
Sub-Investigator: Therese Grahn            
Principal Investigator: Gulber Asanovska, MD            
Sponsors and Collaborators
Sahlgrenska University Hospital, Sweden
Karolinska University Hospital
Malmö University Hospital, Sweden
Investigators
Study Director: Elin Löf, PhD Addiction Biology Unit, University of Gothenburg and Beroendekliniken, Sahlgrenska University Hospital, Sweden
Principal Investigator: Bo Söderpalm, MD, PhD Addiction Biology Unit, University of Gothenburg and Beroendekliniken, Sahlgrenska University Hospital, Sweden
  More Information

Publications:
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 Jan 6; [Epub ahead of print]
Löf E, Olausson P, deBejczy A, Stomberg R, McIntosh JM, Taylor JR, Söderpalm 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. Epub 2007 Aug 17.
Löf E, Chau PP, Stomberg R, Söderpalm 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. Epub 2006 Oct 28.
Söderpalm 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. Review.
Ericson M, Blomqvist O, Engel JA, Söderpalm 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.
Blomqvist O, Ericson M, Engel JA, Söderpalm B. Accumbal dopamine overflow after ethanol: localization of the antagonizing effect of mecamylamine. Eur J Pharmacol. 1997 Sep 10;334(2-3):149-56.
Blomqvist O, Söderpalm B, Engel JA. Ethanol-induced locomotor activity: involvement of central nicotinic acetylcholine receptors? Brain Res Bull. 1992 Aug;29(2):173-8.
Blomqvist O, Engel JA, Nissbrandt H, Söderpalm B. The mesolimbic dopamine-activating properties of ethanol are antagonized by mecamylamine. Eur J Pharmacol. 1993 Nov 9;249(2):207-13.
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. Epub 2007 Jul 11.
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.
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.
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.
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. Epub 2006 Dec 8.
Tonstad S. Varenicline for smoking cessation. Expert Rev Neurother. 2007 Feb;7(2):121-7. Review.
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.
Gonzales D, Rennard SI, Jorenby DE, Reeves KR. Comment: Oral varenicline for smoking cessation. Ann Pharmacother. 2007 Apr;41(4):720-1. Epub 2007 Mar 20. No abstract available.
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.
Larsson A, Jerlhag E, Svensson L, Söderpalm 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.
Larsson A, Svensson L, Söderpalm 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.
Larsson A, Edström L, Svensson L, Söderpalm 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. Epub 2005 Jul 25.
Bohn MJ, Babor TF, Kranzler HR. The Alcohol Use Disorders Identification Test (AUDIT): validation of a screening instrument for use in medical settings. J Stud Alcohol. 1995 Jul;56(4):423-32.
Anton RF, Moak DH, Latham P. The Obsessive Compulsive Drinking Scale: a self-rated instrument for the quantification of thoughts about alcohol and drinking behavior. Alcohol Clin Exp Res. 1995 Feb;19(1):92-9.
Wilson CB, Gutin P, Boldrey EB, Drafts D, Levin VA, Enot KJ. Single-agent chemotherapy of brain tumors. A five-year review. Arch Neurol. 1976 Nov;33(11):739-44.

Responsible Party: Addiction Biology Unit, Sahlgrenska University Hospital, Sweden ( Bo Söderpalm/ MD, PhD, sponsor )
Study ID Numbers: GOTABU-BO2
Study First Received: February 17, 2009
Last Updated: March 18, 2009
ClinicalTrials.gov Identifier: NCT00846859     History of Changes
Health Authority: Sweden: Medical Products Agency

Keywords provided by Sahlgrenska University Hospital, Sweden:
alcohol dependence
nicotine dependence
alcohol abuse
varenicline
Champix
Chantix
smoking
drinking
snuffing
diary
phosphatidyl ethanol
PEth

Study placed in the following topic categories:
Nicotine polacrilex
Smoking
Nicotine
Mental Disorders
Alcoholism
Substance-Related Disorders
Drinking Behavior
Disorders of Environmental Origin
Alcohol-Related Disorders
Alcohol Drinking
Varenicline
Ethanol

Additional relevant MeSH terms:
Mental Disorders
Alcoholism
Substance-Related Disorders
Drinking Behavior
Disorders of Environmental Origin
Alcohol-Related Disorders
Alcohol Drinking

ClinicalTrials.gov processed this record on May 07, 2009