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
Outcome
Missed primary endpoint
Stopped (Enrollment): “The study was closed to recruitment due to feasibility problems.”
paper Analysis of those who completed the study indicated that pioglitazone was associated with elevated, rather than suppressed alcohol cravings in response to alcohol-associated stimuli. PMID 32445052 ↗
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
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Pioglitazone | Small molecule | 45 mg | — |