COMBINE (Acamprosate/Naltrexone)

NCT00006206 | Completed Phase 3

• 13 other identifiers: NIAAACombU10AA011721U10AA011783U10AA011715U10AA011799U10AA011773U10AA011776U10AA011777U10AA011727U10AA011716U10AA011787U10AA011768U10AA011756
• Study Type: interventional
• Target: 1,375
• Locations: 1 country
• Sites: 12

Brief 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.

Conditions

Alcoholism

Outcome Measures

Primary Outcomes (2)

• Percent days abstinent

• Time to relapse to heavy drinking

Secondary Outcomes (4)

• measures of drinking outcomes ((duration of abstinence, measures of frequency and intensity, et al.)

• psychological assessments

• quality of life

• measures of adverse experiences

Interventions

naltrexone (Revia) DRUG

acamprosate (Campral) DRUG

Eligibility Criteria

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

You may qualify if:

• Male and female outpatients \> 18 years of age.
• Participants will have a current DSM-IV diagnosis of alcohol dependence.
• Participants will have signed a witnessed informed consent.
• Participants must have been drinking a minimum of \> 14 drinks (females) or \> 21 drinks (males) on average per week over a consecutive 30-day period in the 90-day period prior to initiation of abstinence, and have two or more days of heavy drinking (defined as 4 drinks for females and 5 drinks for males) in the 90-day period prior to initiation of abstinence.
• Participants must have had a minimum of 4 consecutive days (96 hours) of abstinence and have a CIWA \< 8 prior to randomization.
• Participants can be abstinent for a maximum of 21 days prior to randomization.
• Participants will have no more than 21 consecutive days of planned absence during the 16 week active treatment period.
• Participants who are able to identify at least one "locator" person to assist in tracking the participant for follow-up assessment.
• Participants who are able to speak and understand English.

You may not qualify if:

• Participants who meet current DSM-IV criteria for bipolar disorder, schizophrenia, bulimia/anorexia, dementia, or a psychological disorder requiring medication.
• Participants requiring concomitant therapy with any medications that pose safety issues (see Appendix B).
• Participants with a current diagnosis of dependence on any drug except for nicotine, cannabis, and alcohol, or habitual caffeine use. If there is a positive urine screen the participant can be retested after the (metabolic) interval appropriate to that drug. If the second urine drug screen is positive the person is excluded.
• Participants who meet DSM-IV criteria for opiate dependence or abuse within the past 6 months, chronic treatment with any opiate-containing medications during the previous month, or urine positive for opioids.
• Participants who have significant medical disorders that will increase the potential risk of study treatment or interfere with study participation, and participants with sensitivity to study medications or related drugs as evidenced by adverse drug experience, especially with opiate-containing analgesics, opioid antagonists, or acamprosate.
• Participants with abnormal AST or ALT (more than 3 times the upper limit of the normal range(ULN)) or elevated bilirubin (more than 10% above the ULN). Tests may be repeated if initial results are out of range.
• 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.
• Participants who intend to engage in additional formal treatment for alcohol-related problems, or who intend to continue in current treatment for alcohol-related problems during the active treatment period. Self-help treatments are not considered formal treatment.
• Participants who have had more than seven days of inpatient treatment for substance use disorders in the 30 days previous to randomization.
• Participants who have prior use of study medication(s) in the last 30 days.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator
• Lipha Pharmaceuticals: collaborator

Study Sites (12)

Substance Abuse Treatment Unit, Yale University

New Haven, Connecticut, 06511, United States

Location

University of Miami School of Medicine

Miami, Florida, 33136, United States

Location

Harvard University/McLean Hospital

Belmont, Massachusetts, 02478, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston University School of Medicine

Boston, Massachusetts, 02118, United States

Location

Center on Alcoholism, Substance Abuse and Addiction, University of New Mexico

Albuquerque, New Mexico, 87106, United States

Location

Treatment and Research Center, University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Roger Williams Medical Center , Brown University

Providence, Rhode Island, 02908, United States

Location

Center for Alcohol Programs, Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Southwest Texas Addiction Research and Technology Center, University of Texas Health Science Center

San Antonio, Texas, 78229, United States

Location

Addictions Treatment Center, University of Washington

Seattle, Washington, 98108, United States

Location

University of Wisconsin-Milwaukee

Milwaukee, Wisconsin, 53233, United States

Location

Related Publications (8)

• 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.

  PMID: 12826990 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.

  PMID: 12878918 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.

  PMID: 12878917 BACKGROUND

• 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.

  PMID: 16670409 RESULT

• 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.

  PMID: 32960976 DERIVED

• 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.

  PMID: 30865232 DERIVED

• 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.

  PMID: 18838638 DERIVED

• 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.

  PMID: 18250251 DERIVED

MeSH Terms

Conditions

Alcoholism

Interventions

Naltrexone; Acamprosate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Taurine; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Ray Anton, M.D.

  Medical University of South Carolina

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 11, 2000
• First Posted: September 12, 2000
• Study Start: August 1, 1997
• Study Completion: May 1, 2006
• Last Updated: May 3, 2010

Record last verified: 2007-11

Locations

US (12)