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Available treatments are of modest efficacy and under-prescribed so there is a pressing need for a well-tolerated and effective treatment option for AUD. Dopamine is hypothesized to be involved in the development of alcohol dependence. To challenge the low-dopamine hypothesis of addiction, this randomized, double-blind, placebo-controlled, 13-week, multicentre clinical trial with four parallel arms is designed to evaluate the efficacy of two substances raising dopamine levels, varenicline and bupropion, alone and in combination vs. placebo on alcohol consumption in AUD. Varenicline, a partial agonist at brain nicotinic acetylcholine receptors increases dopamine release, whereas bupropion is a centrally-acting, norepinephrine-dopamine reuptake inhibitor. Varenicline is previously shown to reduce alcohol intake in individuals with AUD. We hypothesize that the effect size of a combination of two drugs affecting dopamine levels in the brain will exceed that of approved AUD therapies.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Consenting individuals with AUD will be recruited via media advertisements. Those fulfilling the eligibility criteria (N = 380) will be randomized to one of four interventions (n = 95 per arm). Treatment will comprise one week of titration (varenicline 0.5\u20122 mg; bupropion SR 150\u2012300 mg) plus 12 weeks at steady state. Efficacy will be evaluated using two primary endpoints of alcohol consumption: Heavy Drinking Days and blood levels of phosphatidylethanol. Secondary objectives, exploratory and subgroup analyses will be also performed. The modified Intention-to-Treat and Per Protocol datasets will be evaluated using Analysis of Covariance. Last patient out is estimated to occur in December, 2022.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Discussion<\/jats:title>\n<jats:p>The COMB Study aims to evaluate the efficacy of the combination of varenicline and bupropion, two drugs affecting dopamine, on alcohol consumption, and to challenge the low-dopamine hypothesis of addiction. Study Code COMB-BO8, EudraCT 2018\u2013000048\u201324, Version 3.2, Lid\u00f6 &amp; deBejczy, 2020-06-16; <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\" xlink:type=\"simple\">https:\/\/clinicaltrials.gov<\/jats:ext-link> identifier NCT04167306.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0296118","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T18:30:15Z","timestamp":1704997815000},"page":"e0296118","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["A randomized, double-blind, placebo-controlled, multicentre trial on the efficacy of varenicline and bupropion in combination and alone for treatment of alcohol use disorder: Protocol for the COMB study"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2858-1524","authenticated-orcid":true,"given":"Andrea","family":"de Bejczy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helga","family":"Lid\u00f6","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"S\u00f6derpalm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,1,11]]},"reference":[{"key":"pone.0296118.ref001","unstructured":"WHO. WHO. Global status report on alcohol and health. 2018. https:\/\/www.who.int\/publications\/i\/item\/9789241565639"},{"issue":"19\u201320","key":"pone.0296118.ref002","first-page":"505","article-title":"Chronic alcoholism\u2014alcohol sequelae\u2014causes of death","volume":"136","author":"OM Lesch","year":"1986","journal-title":"Wien Med Wochenschr"},{"issue":"2","key":"pone.0296118.ref003","first-page":"135","article-title":"The risks associated with alcohol use and alcoholism","volume":"34","author":"J. Rehm","year":"2011","journal-title":"Alcohol Res Health"},{"issue":"4","key":"pone.0296118.ref004","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1093\/alcalc\/agt021","article-title":"Reduction of drinking in problem drinkers and all-cause mortality","volume":"48","author":"J Rehm","year":"2013","journal-title":"Alcohol Alcohol"},{"issue":"2","key":"pone.0296118.ref005","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0306-4603(96)00013-5","article-title":"Drinking goal selection in behavioral self-management treatment of chronic alcoholics","volume":"22","author":"DC Hodgins","year":"1997","journal-title":"Addict Behav"},{"issue":"2","key":"pone.0296118.ref006","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1093\/alcalc\/agp096","article-title":"Initial preference for drinking goal in the treatment of alcohol problems: I. Baseline differences between abstinence and non-abstinence groups","volume":"45","author":"N Heather","year":"2010","journal-title":"Alcohol Alcohol"},{"issue":"1","key":"pone.0296118.ref007","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1177\/0269881113512038","article-title":"Doing it by numbers: a simple approach to reducing the harms of alcohol","volume":"28","author":"DJ Nutt","year":"2014","journal-title":"J Psychopharmacol"},{"issue":"8","key":"pone.0296118.ref008","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.biopsych.2012.10.020","article-title":"Extending the treatment options in alcohol dependence: a randomized controlled study of as-needed nalmefene","volume":"73","author":"K Mann","year":"2013","journal-title":"Biol Psychiatry"},{"issue":"6","key":"pone.0296118.ref009","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/0002-9343(90)90534-K","article-title":"Disulfiram treatment of alcoholism","volume":"88","author":"C Wright","year":"1990","journal-title":"Am J Med"},{"key":"pone.0296118.ref010","unstructured":"Socialstyrelsen. Kostnader f\u00f6r alkohol och narkotika, ber\u00e4kningar av samh\u00e4llets direkta kostnader. 2010. http:\/\/wwwsocialstyrelsense\/Lists\/Artikelkatalog\/Attachments\/17961\/2010-3-15.pdf."},{"issue":"12","key":"pone.0296118.ref011","first-page":"CD001867","article-title":"Opioid antagonists for alcohol dependence","author":"S Rosner","year":"2010","journal-title":"Cochrane Database Syst Rev"},{"issue":"4","key":"pone.0296118.ref012","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1517\/14728214.2010.500811","article-title":"Emerging drugs to treat alcoholism","volume":"15","author":"M Soyka","year":"2010","journal-title":"Expert Opin Emerg Drugs"},{"issue":"18","key":"pone.0296118.ref013","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1001\/jama.2014.3628","article-title":"Pharmacotherapy for adults with alcohol use disorders in outpatient settings: a systematic review and meta-analysis","volume":"311","author":"DE Jonas","year":"2014","journal-title":"JAMA"},{"issue":"11","key":"pone.0296118.ref014","first-page":"858","article-title":"The treatment gap in mental health care","volume":"82","author":"R Kohn","year":"2004","journal-title":"Bull World Health Organ"},{"key":"pone.0296118.ref015","first-page":"1","article-title":"Catecholamines and behavior","volume":"4","author":"J Engel","year":"1977","journal-title":"Curr Dev Psychopharmacol"},{"issue":"4","key":"pone.0296118.ref016","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1037\/0033-295X.94.4.469","article-title":"A psychomotor stimulant theory of addiction","volume":"94","author":"RA Wise","year":"1987","journal-title":"Psychol Rev"},{"issue":"3","key":"pone.0296118.ref017","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s00213-013-3041-9","article-title":"\u03bc-opioid receptors in the stimulation of mesolimbic dopamine activity by ethanol and morphine in Long-Evans rats: a delayed effect of 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Soderpalm","year":"2013","journal-title":"Curr Top Behav Neurosci"},{"issue":"11","key":"pone.0296118.ref021","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1111\/acer.13483","article-title":"The glycine receptor\u2014a functionally important primary brain target of ethanol","volume":"41","author":"B Soderpalm","year":"2017","journal-title":"Alcohol Clin Exp Res"},{"issue":"30","key":"pone.0296118.ref022","doi-asserted-by":"crossref","first-page":"12518","DOI":"10.1073\/pnas.0705368104","article-title":"Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking","volume":"104","author":"P Steensland","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"pone.0296118.ref023","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.biopsych.2009.01.029","article-title":"Varenicline reduces alcohol self-administration in heavy-drinking smokers","volume":"66","author":"SA McKee","year":"2009","journal-title":"Biol Psychiatry"},{"issue":"11","key":"pone.0296118.ref024","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1111\/acer.12854","article-title":"Varenicline for treatment of alcohol dependence: a randomized, placebo-controlled trial","volume":"39","author":"A de Bejczy","year":"2015","journal-title":"Alcohol Clin Exp Res"},{"issue":"4","key":"pone.0296118.ref025","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1097\/ADM.0b013e31829623f4","article-title":"A double-blind, placebo-controlled trial assessing the efficacy of varenicline tartrate for alcohol dependence","volume":"7","author":"RZ Litten","year":"2013","journal-title":"J Addict Med"},{"issue":"3","key":"pone.0296118.ref026","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.neuropharm.2006.10.016","article-title":"Pharmacological profile of the alpha4beta2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation aid","volume":"52","author":"H Rollema","year":"2007","journal-title":"Neuropharmacology"},{"issue":"3","key":"pone.0296118.ref027","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1002\/cne.10138","article-title":"Expression of neuronal nicotinic acetylcholine receptor subunit mRNAs within midbrain dopamine neurons","volume":"444","author":"L Azam","year":"2002","journal-title":"J Comp Neurol"},{"issue":"6","key":"pone.0296118.ref028","doi-asserted-by":"crossref","first-page":"e834","DOI":"10.1038\/tp.2016.104","article-title":"A mega-analysis of fixed-dose trials reveals dose-dependency and a rapid onset of action for the antidepressant effect of three selective serotonin reuptake inhibitors","volume":"6","author":"F Hieronymus","year":"2016","journal-title":"Transl Psychiatry"},{"issue":"9","key":"pone.0296118.ref029","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S2215-0366(18)30269-4","article-title":"Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis","volume":"5","author":"S Cortese","year":"2018","journal-title":"Lancet Psychiatry"},{"issue":"9","key":"pone.0296118.ref030","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1056\/NEJM199903043400903","article-title":"A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation","volume":"340","author":"DE Jorenby","year":"1999","journal-title":"N Engl J Med"},{"issue":"5","key":"pone.0296118.ref031","doi-asserted-by":"crossref","first-page":"e12807","DOI":"10.1111\/adb.12807","article-title":"Combined administration of varenicline and bupropion produces additive effects on accumbal dopamine and abolishes the alcohol deprivation effect in rats","volume":"25","author":"B Soderpalm","year":"2020","journal-title":"Addict Biol"},{"issue":"6","key":"pone.0296118.ref032","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1007\/s007020070068","article-title":"Pharmacological validation of a new animal model of alcoholism","volume":"107","author":"R Spanagel","year":"2000","journal-title":"J Neural Transm"},{"issue":"1\u20132","key":"pone.0296118.ref033","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0009-8981(00)00291-6","article-title":"Normalization rate and cellular localization of phosphatidylethanol in whole blood from chronic alcoholics","volume":"299","author":"A Varga","year":"2000","journal-title":"Clin Chim Acta"},{"issue":"1","key":"pone.0296118.ref034","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/j.1369-1600.2006.00040.x","article-title":"Phosphatidylethanol as a sensitive and specific biomarker: comparison with gamma-glutamyl transpeptidase, mean corpuscular volume and carbohydrate-deficient transferrin","volume":"12","author":"S Hartmann","year":"2007","journal-title":"Addict Biol"},{"issue":"8","key":"pone.0296118.ref035","doi-asserted-by":"crossref","first-page":"549","DOI":"10.3109\/15622975.2013.838302","article-title":"Consensus paper of the WFSBP task force on biological markers: biological markers for alcoholism","volume":"14","author":"E Hashimoto","year":"2013","journal-title":"World J Biol Psychiatry"},{"issue":"5","key":"pone.0296118.ref036","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1111\/acer.13620","article-title":"Differences in the synthesis and elimination of phosphatidylethanol 16:0\/18:1 and 16:0\/18:2 after acute doses of alcohol","volume":"42","author":"N Hill-Kapturczak","year":"2018","journal-title":"Alcohol Clin Exp Res"},{"issue":"9","key":"pone.0296118.ref037","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1111\/j.1530-0277.2012.01768.x","article-title":"Formation of phosphatidylethanol and its subsequent elimination during an extensive drinking experiment over 5 days","volume":"36","author":"H Gnann","year":"2012","journal-title":"Alcohol Clin Exp Res"},{"issue":"1","key":"pone.0296118.ref038","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/j.1369-1600.2009.00185.x","article-title":"Phosphatidylethanol: normalization during detoxification, gender aspects and correlation with other biomarkers and self-reports","volume":"15","author":"FM Wurst","year":"2010","journal-title":"Addict Biol"},{"issue":"2","key":"pone.0296118.ref039","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1017\/S0033291704002892","article-title":"The World Health Organization Adult ADHD Self-Report Scale (ASRS): a short screening scale for use in the general population","volume":"35","author":"RC Kessler","year":"2005","journal-title":"Psychol Med"},{"issue":"4","key":"pone.0296118.ref040","doi-asserted-by":"crossref","first-page":"423","DOI":"10.15288\/jsa.1995.56.423","article-title":"The Alcohol Use Disorders Identification Test (AUDIT): validation of a screening instrument for use in medical settings","volume":"56","author":"MJ Bohn","year":"1995","journal-title":"J Stud Alcohol"},{"key":"pone.0296118.ref041","volume-title":"The Alcohol Use Disorders Identification Test. Guidelines for use in primary care","author":"TF Babor","year":"2001"},{"issue":"1","key":"pone.0296118.ref042","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1159\/000081413","article-title":"Evaluation of the Drug Use Disorders Identification Test (DUDIT) in criminal justice and detoxification settings and in a Swedish population sample","volume":"11","author":"AH Berman","year":"2005","journal-title":"Eur Addict Res"},{"key":"pone.0296118.ref043","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1192\/bjp.134.4.382","article-title":"A new depression scale designed to be sensitive to change","volume":"134","author":"SA Montgomery","year":"1979","journal-title":"Br J Psychiatry"},{"issue":"2","key":"pone.0296118.ref044","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1002\/pchj.207","article-title":"The structural invariance of the Temporal Experience of Pleasure Scale across time and culture","volume":"7","author":"Z Li","year":"2018","journal-title":"Psych J"},{"key":"pone.0296118.ref045","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/978-1-4612-0357-5_3","volume-title":"Measuring Alcohol Consumption: Psychosocial and Biological Methods","author":"LC Sobell","year":"1992"},{"issue":"10","key":"pone.0296118.ref046","first-page":"989","article-title":"Measurement of feelings using visual analogue scales","volume":"62","author":"RC Aitken","year":"1969","journal-title":"Proc R Soc Med"},{"issue":"8","key":"pone.0296118.ref047","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1176\/appi.ajp.162.8.1515","article-title":"Correlation of alcohol craving with striatal dopamine synthesis capacity and D2\/3 receptor availability: a combined [18F]DOPA and [18F]DMFP PET study in detoxified alcoholic patients","volume":"162","author":"A Heinz","year":"2005","journal-title":"Am J Psychiatry"},{"issue":"46","key":"pone.0296118.ref048","doi-asserted-by":"crossref","first-page":"12700","DOI":"10.1523\/JNEUROSCI.3371-07.2007","article-title":"Profound decreases in dopamine release in striatum in detoxified alcoholics: possible orbitofrontal involvement","volume":"27","author":"ND Volkow","year":"2007","journal-title":"J Neurosci"},{"issue":"8","key":"pone.0296118.ref049","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/S2215-0366(16)00104-8","article-title":"Neurobiology of addiction: a neurocircuitry analysis","volume":"3","author":"GF Koob","year":"2016","journal-title":"Lancet Psychiatry"},{"issue":"9","key":"pone.0296118.ref050","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1001\/archpsyc.63.9.999","article-title":"High levels of dopamine D2 receptors in unaffected members of alcoholic families: possible protective factors","volume":"63","author":"ND Volkow","year":"2006","journal-title":"Arch Gen Psychiatry"},{"issue":"10","key":"pone.0296118.ref051","doi-asserted-by":"crossref","first-page":"3474","DOI":"10.1523\/JNEUROSCI.16-10-03474.1996","article-title":"Ethanol self-administration restores withdrawal-associated deficiencies in accumbal dopamine and 5-hydroxytryptamine release in dependent rats","volume":"16","author":"F Weiss","year":"1996","journal-title":"J Neurosci"},{"issue":"2","key":"pone.0296118.ref052","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1111\/adb.12304","article-title":"The monoamine stabilizer (-)-OSU6162 counteracts downregulated dopamine output in the nucleus accumbens of long-term drinking Wistar rats","volume":"21","author":"K Feltmann","year":"2016","journal-title":"Addict Biol"},{"issue":"10","key":"pone.0296118.ref053","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1176\/ajp.161.10.1783","article-title":"Correlation between dopamine D(2) receptors in the ventral striatum and central processing of alcohol cues and 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