COMBINE (Acamprosate/Naltrexone)

Alcoholism Clinical Trial

Official title:

COMBINE: Effect of Combined Pharmacotherapies and Behavioral Interventions

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006206
• Other study ID #: NIAAAComb
• Secondary ID: U10AA011721U10AA
• Status: Completed
• Phase: Phase 3
• First received: September 11, 2000
• Last updated: April 30, 2010
• Start date: August 1997
• Est. completion date: May 2006

Study information

• Verified date: November 2007
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT00000453

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1375
• Est. completion date: May 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria

The following inclusion criteria are to be met:

1. Male and female outpatients > 18 years of age.

2. Participants will have a current DSM-IV diagnosis of alcohol dependence.

3. Participants will have signed a witnessed informed consent.

4. 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.

5. Participants must have had a minimum of 4 consecutive days (96 hours) of abstinence and have a CIWA < 8 prior to randomization.

6. Participants can be abstinent for a maximum of 21 days prior to randomization.

7. Participants will have no more than 21 consecutive days of planned absence during the 16 week active treatment period.

8. Participants who are able to identify at least one "locator" person to assist in tracking the participant for follow-up assessment.

9. Participants who are able to speak and understand English.

Exclusion criteria

The following exclusion criteria rule out participants:

1. Participants who meet current DSM-IV criteria for bipolar disorder, schizophrenia, bulimia/anorexia, dementia, or a psychological disorder requiring medication.

2. Participants requiring concomitant therapy with any medications that pose safety issues (see Appendix B).

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. Participants who have had more than seven days of inpatient treatment for substance use disorders in the 30 days previous to randomization.

10. Participants who have prior use of study medication(s) in the last 30 days.

Any question concerning the interpretation of or application of the inclusion/exclusion criteria will be referred to the medical expert at the Coordinating Center. If he is unavailable, the question will be referred to the Chairperson of the Treatment Subcommittee.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alcoholism

Intervention

Drug:
• naltrexone (Revia)

• acamprosate (Campral)

Locations

Country	Name	City	State
United States	Center on Alcoholism, Substance Abuse and Addiction, University of New Mexico	Albuquerque	New Mexico
United States	Harvard University/McLean Hospital	Belmont	Massachusetts
United States	Boston University School of Medicine	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Center for Alcohol Programs, Medical University of South Carolina	Charleston	South Carolina
United States	University of Miami School of Medicine	Miami	Florida
United States	University of Wisconsin-Milwaukee	Milwaukee	Wisconsin
United States	Substance Abuse Treatment Unit, Yale University	New Haven	Connecticut
United States	Treatment and Research Center, University of Pennsylvania	Philadelphia	Pennsylvania
United States	Roger Williams Medical Center , Brown University	Providence	Rhode Island
United States	Southwest Texas Addiction Research and Technology Center, University of Texas Health Science Center	San Antonio	Texas
United States	Addictions Treatment Center, University of Washington	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	Lipha Pharmaceuticals, National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Country where clinical trial is conducted

United States, 

References & Publications (4)

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 Resear — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent days abstinent
Primary	Time to relapse to heavy drinking
Secondary	measures of drinking outcomes ((duration of abstinence, measures of frequency and intensity, et al.)
Secondary	psychological assessments
Secondary	quality of life
Secondary	measures of adverse experiences

External Links

•   COMBINE is a project studying new treatments for alcohol dependence. COMBINE is sponsored by the National Institute of Alcohol Abuse and Alcoholism