COMBINE (Acamprosate/Naltrexone)
Summary
Combine is a multicenter, randomized clinical trial that will evaluate combinations of three interventions for treating alcohol dependence. The goal is to determine whether improvement in treatment outcomes can be achieved by various combinations of drug and behavioral interventions. Two of the interventions will consist of pharmacological treatment with naltrexone (Revia) or acamprosate (Campral). The third intervention is a multicomponent behavioral therapy including such components as motivational enhancement therapy, cognitive behavioral therapy, and referral to self-help groups, including AA. All three interventions will include a component supporting compliance to medications and reduction in drinking.
Timeline
- Start
- 1997-08
- Primary completion
- —
- Completion
- 2006-05
Outcome
Mixed primary results
paper Naltrexone also reduced risk of a heavy drinking day (hazard ratio, 0.72; 97.5% CI, 0.53-0.98; P = .02) over time PMID 16670409 ↗
paper Acamprosate showed no significant effect on drinking vs placebo, either by itself or with any combination of naltrexone, CBI, or both. PMID 16670409 ↗
Publications
- Background Johnson BA, O'Malley SS, Ciraulo DA, Roache JD, Chambers RA, Sarid-Segal O, Couper D. Dose-ranging kinetics and behavioral pharmacology of naltrexone and acamprosate, both alone and combined, in alcohol-dependent subjects. J Clin Psychopharmacol. 2003 Jun;23(3):281-93. doi: 10.1097/01.jcp.0000084029.22282.bb.
- Background COMBINE Study Research Group. Testing combined pharmacotherapies and behavioral interventions for alcohol dependence (the COMBINE study): a pilot feasibility study. Alcohol Clin Exp Res. 2003 Jul;27(7):1123-31. doi: 10.1097/01.ALC.0000078020.92938.0B.
- Background COMBINE Study Research Group. Testing combined pharmacotherapies and behavioral interventions in alcohol dependence: rationale and methods. Alcohol Clin Exp Res. 2003 Jul;27(7):1107-22. doi: 10.1097/00000374-200307000-00011.
- Results Anton RF, O'Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM, Gastfriend DR, Hosking JD, Johnson BA, LoCastro JS, Longabaugh R, Mason BJ, Mattson ME, Miller WR, Pettinati HM, Randall CL, Swift R, Weiss RD, Williams LD, Zweben A; COMBINE Study Research Group. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA. 2006 May 3;295(17):2003-17. doi: 10.1001/jama.295.17.2003.
- Acin MT, Rueda JR, Saiz LC, Parent Mathias V, Alzueta N, Sola I, Garjon J, Erviti J. Alcohol intake reduction for controlling hypertension. Cochrane Database Syst Rev. 2020 Sep 21;9(9):CD010022. doi: 10.1002/14651858.CD010022.pub2.
- Falk DE, O'Malley SS, Witkiewitz K, Anton RF, Litten RZ, Slater M, Kranzler HR, Mann KF, Hasin DS, Johnson B, Meulien D, Ryan M, Fertig J; Alcohol Clinical Trials Initiative (ACTIVE) Workgroup. Evaluation of Drinking Risk Levels as Outcomes in Alcohol Pharmacotherapy Trials: A Secondary Analysis of 3 Randomized Clinical Trials. JAMA Psychiatry. 2019 Apr 1;76(4):374-381. doi: 10.1001/jamapsychiatry.2018.3079.
- Zarkin GA, Bray JW, Aldridge A, Mitra D, Mills MJ, Couper DJ, Cisler RA; COMBINE Cost-Effectiveness Research Group. Cost and cost-effectiveness of the COMBINE study in alcohol-dependent patients. Arch Gen Psychiatry. 2008 Oct;65(10):1214-21. doi: 10.1001/archpsyc.65.10.1214.
- Anton RF, Oroszi G, O'Malley S, Couper D, Swift R, Pettinati H, Goldman D. An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence: results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study. Arch Gen Psychiatry. 2008 Feb;65(2):135-44. doi: 10.1001/archpsyc.65.2.135.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Acamprosate | Small molecule | 3 g | — |
| Subject | Naltrexone | Small molecule | 100 mg | — |