PLANNING A CLINICAL TRIAL TO PREVENT POSTTRANSPLANT ALD

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Hepatic transplant for persons suffering from alcohol dependence (AD) remains controversial medical issue. Despite three year data collected by the present PI and associates showing uniquely high abstinent rates in this highly selected population, any alcohol use post-transplant reaches as high as 35-40 percent. While rates of alcohol related mortality post-transplant, such as that from Alcoholic Liver Disease (ALD), remain low at about 1-5 percent, any mortality due to a preventable return to ethanol ingestion in an AD group is medically unacceptable and a threat to providing liver transplant for ALD. The outcome figures cited above suggest two phenomena: 1) the limit of AD patient selection in assuring long term abstinence, and 2) the need for specific treatment of this unique population whose natural abstinence rate far exceeds those found in non-transplant AD cases. Further, longitudinal data suggest 3) that alcohol related mortality occurs after the first year post-transplant, so called late deaths. A clear need exists to design and implement effective treatment for this unique clinical population that takes into account their already high abstinent rate and their course of increasing risk for alcoholic relapse and late death due to recurrent ALD or other AD related injury. The consortium of liver transplant centers proposes to design and propose a randomized clinical trial of focused, active, long-term follow-up care in a test group of 205 AD liver transplant recipients versus standard care given to a control group of 205 AD liver graft recipients; ethanol use will be the primary outcome variable. This study, conducted in seven Centers, would be executed over five years with a goal of at least seven years treatment exposure. While intent, good will, and patient flow are in place, the consortium Centers unanimously believe that proper organization is not in place and must be developed. Therefore, the group of Centers supports the present proposal for a planning grant that would establish the structures, communications, methods, policies and procedures for the successful completion of a clinical trial specifically designed for AD liver transplant recipients. The present proposal seeks to create among the Centers 1) an organizational structure, 2) a shared theoretical framework, 3) mutually agreed upon treatment and control protocols 4) detailed logistical planning for the protocols, 5) reliable measures of ethanol use, 6) effective communications, data transfer and analysis capabilities and 7) an external review panel of experts. On completion of these tasks, the PI and consortium members expect to have in place not only a well constructed proposal but a demonstrably active, well functioning clinical research consortium capable of executing the proposed clinical trial.