Role of Proinflammatory Signaling in Alcohol Craving

Summary

Background: \- Drinking too much alcohol can injure cells in the body. Inflammation is the body s reaction to injured cells. Studies show that inflammation can cause cravings for alcohol. Researchers want to see if pioglitazone, a drug that decreases inflammation, can reduce alcohol craving. If so, it might help develop new ways to help alcoholics with craving. Objectives: \- To see if pioglitazone can reduce alcohol craving. Eligibility: \- Adults between 21 and 65 years of age who are alcoholic and have been drinking within the past month. Design: * Participants will be screened with a physical exam and medical history. Blood samples will also be collected. * All participants will have inpatient treatment at the National Institutes of Health Clinical Center for the 5 weeks of the study. They will have standard treatment for alcoholism during their inpatient stay. * Half of the people in this study will have pioglitazone. The other half will have a placebo. * Participants will have different studies during their stay. These studies will include the following: * Personalized audio recordings of stressful, alcohol-related, and neutral events to monitor mood * Imaging studies to test alcohol cravings * Questionnaires about mood and alcohol cravings * Lumbar puncture to collect spinal fluid * Inflammation test to see if the study drug can block alcohol cravings * After the end of the 5-week study, all participants will be offered follow-up outpatient care through the Clinical Center, or referral to outside treatment.

Timeline

Start

2012-05

Primary completion

2015-09

Completion

2015-09

Publications

• Background Capuron L, Miller AH. Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol Ther. 2011 May;130(2):226-38. doi: 10.1016/j.pharmthera.2011.01.014. Epub 2011 Feb 17.
• Background Crews FT, Zou J, Qin L. Induction of innate immune genes in brain create the neurobiology of addiction. Brain Behav Immun. 2011 Jun;25 Suppl 1(Suppl 1):S4-S12. doi: 10.1016/j.bbi.2011.03.003. Epub 2011 Mar 21.
• Background Dantzer R, Kelley KW. Twenty years of research on cytokine-induced sickness behavior. Brain Behav Immun. 2007 Feb;21(2):153-60. doi: 10.1016/j.bbi.2006.09.006. Epub 2006 Nov 7.
• Schwandt ML, Diazgranados N, Umhau JC, Kwako LE, George DT, Heilig M. PPARgamma activation by pioglitazone does not suppress cravings for alcohol, and is associated with a risk of myopathy in treatment seeking alcohol dependent patients: a randomized controlled proof of principle study. Psychopharmacology (Berl). 2020 Aug;237(8):2367-2380. doi: 10.1007/s00213-020-05540-w. Epub 2020 May 22.

Drugs

Indications