UNC Coordinates National Study to Evaluate Combined Therapies for Alcoholism

The University of North Carolina at Chapel Hill is the Co-ordinating Center for COMBINE: the collaborative study to Combine Medications and Behavioral Interventions for Alcoholism. The Department of Biostatistics and the Center for Alcohol Studies are working together along with investigators from 11 other universities on this key project designed to determine which combinations of various therapies are most likely to help alcoholic patients stay in treatment, remain abstinent or reduce their drinking and improve their quality of life.

The UNC Collaborative Studies Coordinating Center Team. Back row left to right: David Couper, J.C. Garbutt, Marston Youngblood; Front row left to right: Carol Antone, Jim Hosking, Barbara Brown.

The quiet hallways of 137 East Franklin Street in Chapel Hill belie the intense, vital activity of its fourth floor inhabitants. Tucked away in the center of the building, with computers whirring everywhere, is the Collaborative Studies Coordinating Center (CSCC) of the University of North Carolina. CSCC is the home of research efforts directed at understanding some of today's most challenging and important health problems, including atherosclerosis, diabetes, stroke, and most recently, alcoholism.

Under the leadership of Dr. James Hosking, Director of Research, the research team at the CSCC is participating in a collaborative study to evaluate the effectiveness of therapeutic interventions for alcoholism. The National Institute of Alcohol Abuse and Alcoholism, a relative newcomer to collaborative studies, is sponsoring the trial known as COMBINE (Combining Medications and Behavioral Interventions). The CSCC's successful track record of collaborative research in metabolic and cardiovascular diseases made it the perfect choice for coordinating drug addiction intervention research, which typically requires large numbers of patients to be followed for long periods of time. The COMBINE trial will follow 1,375 patients over a 2-year period at 11 nationwide centers. Dr. J.C. Garbutt of UNC's Skipper Bowles Center for Alcohol Studies serves with Dr. Hosking as co-investigator for COMBINE. He will provide clinical expertise and guidance to the coordinating center.

The primary objective of COMBINE is to assess the effectiveness of combinations of behavioral and pharmacological therapies in the treatment of alcoholism. Behavioral modification approaches, such as Alcoholics Anonymous or cognitive-behavioral therapy, have historically comprised the mainstay of treatment options for alcoholics. Only in the last few years have pharmacological treatments, such as naltrexone (available in the United States and in Europe) and acamprosate (available in Europe) received regulatory clearance to be used in alcoholism. Both behavioral and pharmacological approaches are effective in some patients, but neither approach is a cure-all. The COMBINE investigators hypothesize that combinations of behavioral and pharmacological interventions will be more effective than any single intervention in helping alcoholics to abstain from alcohol.

Name:   James D. Hosking   Birth:   August 23, 1952,   Chicago, IL Education: BS in Psychology, Georgia Institute of Technology, Atlanta, GA, 1974; MA in Quantitative Psychology, University of North Carolina at Chapel Hill, Chapel Hill NC, 1978; PhD in Quantitative Psychology, University of North Carolina at Chapel Hill, Chapel Hill NC, 1980. Recent Experience: Associate Director, Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina at Chapel Hill, 1991-present; Research Associate Professor, Department of Biostatistics, University of North Carolina at Chapel Hill, 1986-present; Principal Investigator, COMBINE Coordinating Center (Multi-center clinical trial sponsored by NIAAA), 1997-present; Principal Investigator, ENRICHD Coordinating Center (Multi-center clinical trial sponsored by NHLBI), 1995-present; Principal Investigator, DAIS Coordinating Center (Multi-center clinical trial sponsored by Laboratoires Fournier and the World Health Organization), 1994-present; Principal Investigator, ACAS Coordinating Center (Multi-center clinical trial sponsored by NINDS), 1995-1998; Principal Investigator, ESPRIT Coordinating Center (Multi-center clinical trial sponsored by Zambon Pharmaceuticals), 1995-1996; Principal Investigator, STILE Coordinating Center (Multi-center clinical trial sponsored by Genetech, Inc.), 1991-1995; Family: Married, with one child.

Alcoholics in the COMBINE study will receive placebo, acamprosate, naltrexone, or acamprosate plus naltrexone as pharmacological therapy combined with either minimal or moderate behavioral therapy. Acamprosate and naltrexone were chosen as pharmacological therapy because there is strong evidence that each medication is effective at reducing some aspect of the alcoholic's compulsion to drink. Acamprosate may be effective in reducing prolonged alcohol withdrawal syndromes including anxiety and alcohol craving. Acamprosate in clinical trials has been found to help individuals maintain abstinence from alcohol in several European studies. Naltrexone may directly block alcohol's positive effects such as euphoria and relaxation by impeding the actions of endogenous opioid peptides. The drug may thereby reduce intake by making alcohol less rewarding to the alcoholic. Naltrexone has been shown to be particularly effective in reducing relapse to heavy drinking among alcoholics in treatment. Pharmacotherapy is not thought to be effective alone, but reducing relapse helps keep patients in therapy.

The behavioral treatments that will be studied with these pharmacological interventions were chosen on the basis of their promise in clinical practice. The "minimal behavioral therapy" in the COMBINE study is based on a model of brief interventions that can be used in primary care settings in the treatment of alcoholism. The minimal behavioral therapy is geared toward increasing patients' compliance with their medication regimen, by providing medical information about alcoholism and medications for alcoholism, and providing referrals to peer support groups. The "moderate behavioral therapy" incorporates features of motivational enhancement, cognitive-behavioral skills training, and facilitation in mutual-help groups. COMBINE will seek to determine, in a controlled environment, whether these behavioral therapies enhance the effectiveness of pharmaceutical intervention alone. The careful standardization of behavioral therapies in the COMBINE study should allow researchers to make more definitive conclusions about the effectiveness of behavioral therapy than have previously been possible.

The primary outcome measures in the COMBINE study will be the percentage of days the patients abstain from alcohol during a 4-month treatment period as well as the time to relapse to heavy drinking (defined as 5 daily drinks for men and 4 daily drinks for women). Says Dr. Hosking, "The time is ripe for a study like COMBINE. Until recently, alcoholics could rely only on behavioral modification to help them fight their craving for alcohol. Now there are medications that can help in the fight against that craving. There has been much speculation about whether behavioral therapies enhance the effectiveness of these medications in helping alcoholics to abstain from drinking. For the first time, with COMBINE we can begin to answer this question."

The CSCC, founded in 1971 as a division of the School of Public Health's Department of Biostatistics, partners with clinical units and governmental or pharmaceutical company sponsors to conduct large-scale epidemiological and clinical studies. As its moniker suggests, the CSCC fulfils a coordinating role by providing strategic advice on scientific and statistical aspects of study plans and by managing the analysis of study data and ensuring their quality. The CSCC collaborates nationwide with clinical programs that contribute medical expertise and treat patients enrolled in the studies, as well as with governmental agencies or pharmaceutical companies that fund them. The involvement of multiple study sites and groups of experts across the United States allows research to be conducted on a large scale, so that thousands of patients can be enrolled in a study and can be followed for long periods of time. The ability to conduct such large-scale, long-term trials facilitates the study of diseases that develop slowly over time or that occur so seldom that they would not normally be amenable to study in smaller trials.

The CSCC has participated over the years in a number of pivotal studies that have influenced current thinking about disease and health and have led to improvements in medical practice. Eleven studies are currently ongoing. One of these studies, the Atherosclerosis Risk in Communities Study (ARIC), is designed to investigate the causes and natural history of atherosclerosis (sometimes called hardening of the arteries), one of the most significant public health threats in the United States. This study has provided important insights about the relationships between cigarette smoking, diet, and atherosclerosis, and about how demographics such as gender and race affect its progression. Hopefully, Project COMBINE will be the first in a long series of clinical trials for alcoholism coordinated by UNC-CH's Clinical Coordinating Center.