NIAAA Launches COMBINE Clinical Trial - Eleven universities to test behavioral and pharmacologic treatments for alcoholism
The National Institute on Alcohol Abuse and Alcoholism (NIAAA) today announces the start of Combining Medications and Behavioral Interventions (COMBINE), a nationwide study that targets persons with the diagnosis alcohol dependence, commonly known as alcoholism. COMBINE is the first national study to evaluate the effectiveness of behavioral treatments alone and in combination with medications. It begins at a time when advances in genetics, neuroscience and treatment research are forging new directions for alcoholism treatment and building expectations among patients, clinical practitioners and the public for improved treatment outcomes.
"More than 8 million American adults meet clinical criteria for alcoholism, a condition characterized by an abnormal appetite for alcohol that leads to significant impairment--tolerance, impaired control over intake, physical dependence and, often, severe craving following sustained abstinence," said NIAAA Director Enoch Gordis, M.D. "Of persons who receive treatment, as many as 50 percent relapse at least once and a minority achieve long-term remission of disease. Identifying and developing effective treatments is the first priority of alcoholism research."
Over the next 24 months at eleven treatment research centers across the United States, the COMBINE study will recruit and randomize 1,375 people who meet current diagnostic criteria for alcohol dependence. Participants will receive one or both of two behavioral treatments (moderate-intensity and lower-intensity) and one or both of two medications (naltrexone and acamprosate) or a placebo. They will attend outpatient sessions for 4 months, then return for three followup visits over the subsequent 12 months.
"COMBINE is based on the accumulated knowledge of two decades in which NIAAA researchers have applied rigorous clinical trial methodology to test treatments for alcoholism," said Richard K. Fuller, M.D., Director of NIAAA’s Division of Clinical and Prevention Research. "In 1996, Project MATCH, another benchmark multisite national trial, demonstrated the effectiveness of facilitated mutual-help involvement and two professionally delivered behavioral treatments [see " NIAAA Reports Project MATCH Main Findings" at Press Releases]."
"Also during the past decade, research on medications to treat alcoholism has rapidly expanded as neuroscientists have advanced understanding of the biology of drinking behavior. From among the most promising pharmacologic and behavioral treatments, COMBINE is expected to define the optimal treatment combinations," said Raymond F. Anton, M.D., Medical University of South Carolina. Dr. Anton serves as chairperson of the COMBINE Steering Committee, a position held previously by Stephanie S. O’Malley, Ph.D., Yale University School of Medicine.
According to current research, the most promising pharmacologic treatments are naltrexone, approved by the U.S. Food and Drug Administration in 1994, and acamprosate, in use in Europe for about 14 years and currently under review by the U.S. Food and Drug Administration. Naltrexone, an opioid blocker, interferes with brain neurotransmitter systems that produce the rewarding effects of alcohol. Researchers have shown that naltrexone-treated patients are less likely to relapse to heavy drinking. Acamprosate is believed to normalize abnormalities in the glutamate (NMDA) and GABA neurotransmitter systems involved in alcohol withdrawal and may ease the discomfort of abstinence, thereby helping to prevent drinking. Among other questions, COMBINE will explore whether treatment effectiveness is improved by pairing a medication that reduces the risk of any drinking with one that reduces the risk of heavy drinking.
The moderate-intensity behavioral treatment developed for COMBINE integrates motivational enhancement therapy, cognitive-behavioral skills training and facilitated patient involvement in mutual-help groups such as Alcoholics Anonymous–treatments shown by NIAAA’s Project MATCH to increase abstinent days and reduce heavy drinking. The lower-intensity behavioral treatment is designed to support sobriety, enhance medication compliance, and be incorporated into the daily routine of health care practitioners in primary and managed care settings.
"Alcoholism results from an interplay of drinker characteristics, including intrinsic neurochemical factors, some of which may be genetically modulated, with environmental risk factors. From brain imaging studies, we know that both medications and behavioral treatments can influence brain function and resulting behaviors. Our expectation is that the behavioral and pharmacologic treatments being tested in COMBINE will complement and perhaps enhance one another," Dr. Gordis said.
The most severe condition in the spectrum of alcohol problems, alcoholism affects about 13 percent of Americans at some time in their lives. Chronic, heavy drinkers are prone to cirrhosis and other liver diseases, neurological disorders, cardiovascular damage, pancreatic disease, and certain cancers. Approximately one in four urban hospital beds is occupied by a patient being treated for the consequences of drinking.
In addition to the 8 million Americans with alcohol dependence, about 6 million meet diagnostic criteria for alcohol abuse disorder, a pattern of harmful or hazardous drinking that persists despite interpersonal, social, employment, or legal problems but does not entail physiological addiction. Millions more engage in risky drinking patterns that could lead to alcohol problems, including impaired productivity, property damage, and injuries.
More than one-half of adult Americans have direct family experience of alcohol problems, which cost American society more than 100,000 lives and approximately $185 billion each year.
The COMBINE study is recruiting people aged 18 years and older. Persons interested in participating may determine their geographic eligibility by calling 1-866-80-STUDY after *8:00 AM (EST) March 8. Participants must be willing to be screened for alcoholism and be abstinent for a minimum of 4 and a maximum of 21 days prior to entering the study. There is no cost for participating in the COMBINE study.
One of 25 institutes and centers at the National Institutes of Health, NIAAA is the lead Federal entity for research on the causes, consequences, prevention and treatment of alcoholism, alcohol abuse, and alcohol-related problems. Through an integrated, multidisciplinary program, NIAAA supports and conducts more than 90 percent of alcohol research in the United States. The results of NIAAA research contribute directly to the treatment and prevention of alcohol problems and the formulation of national health policy.
For interviews with Dr. Gordis, Dr. Fuller and the COMBINE principal investigators, telephone the NIAAA Press Office, (301) 443-9970 or (301) 443-0595. For additional information about alcohol research, please visit http://www.niaaa.nih.gov.
COMBINE Sites and Principal Investigators
Medical University of South Carolina
Charleston, SC
Raymond F. Anton, M.D
Boston University
Boston, MA
Domenic Ciraulo, M.D.
University of Washington
Seattle, WA
Dennis M. Donovan, M.D.
University of Texas
San Antonio, TX
Bankole Johnson, M.D., Ph.D.
University of Miami
Miami, FL
Barbara J. Mason, Ph.D.
University of New Mexico
Albuquerque, NM
William R. Miller, Ph.D.
Yale University
New Haven, CT
Stephanie S. O’Malley, Ph.D.
University of Pennsylvania
Philadelphia, PA
Helen M. Pettinati, Ph.D.
Brown University
Providence, RI
Robert Swift, M.D., Ph.D.
Harvard University
Boston, MA
Roger D. Weiss, M.D.
University of Wisconsin-Milwaukee
Milwaukee, WI
Allen Zweben, D.S.W.
Coordinating Center
University of North Carolina
Chapel Hill, NC
James D. Hosking, Ph.D.
NIAAA Staff Collaborator
Bethesda, MD
Margaret E. Mattson, Ph.D.