Effects of Colchicine in Non-Diabetic Adults With Metabolic Syndrome

Summary

Background: \- Being overweight may cause low-level inflammation. This inflammation may cause some of the medical problems of obesity, like high blood sugar (diabetes) and heart disease. This study will test whether a medication called colchicine can improve metabolism in adults who are overweight but have not yet developed diabetes. Objectives: \- To learn whether colchicine improves sugar regulation and metabolism. Eligibility: \- Healthy overweight adults18 to 100 years old. Design: * Participants must fast before each visit, including the screening visit. * Participants will be screened with blood tests,urine tests, medical history, and physical exam. They will have to drink sugar water, and have blood drawn to find out if they are healthy. * For visit 1, participants will have a medical history and physical exam and answer questions. They will have blood taken with an intravenous (IV) line, give urine sample, and give 2 stool samples.. * Also, subjects will get sugar water through one IV. Blood will be drawn from the other. This measures sugar and insulin levels. During this, participants will lie in a bed and can watch TV. * Participants will have a full-body X-ray, lying on a table while a camera passes over them. They will also have an abdominal CT scan, lying on a table that moves through a ring that takes pictures. * Participants will have a small fat tissue sample taken from their abdomen. It is like getting a mini-liposuction. * Participants will be given the study drug or placebo. They will take it twice daily for 3 months. * For visit 2, participants will have blood tests, urine tests, medical history, and physical exam. * For visit 3, participants will repeat the tests in visit 1.

Timeline

Start

2014-05-31

Primary completion

2018-08-15

Completion

2018-08-15

Publications

• Background Wen H, Gris D, Lei Y, Jha S, Zhang L, Huang MT, Brickey WJ, Ting JP. Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat Immunol. 2011 May;12(5):408-15. doi: 10.1038/ni.2022. Epub 2011 Apr 10.
• Background Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K, Mynatt RL, Ravussin E, Stephens JM, Dixit VD. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med. 2011 Feb;17(2):179-88. doi: 10.1038/nm.2279. Epub 2011 Jan 9.
• Background Demidowich AP, Davis AI, Dedhia N, Yanovski JA. Colchicine to decrease NLRP3-activated inflammation and improve obesity-related metabolic dysregulation. Med Hypotheses. 2016 Jul;92:67-73. doi: 10.1016/j.mehy.2016.04.039. Epub 2016 Apr 25.
• Results Demidowich AP, Levine JA, Onyekaba GI, Khan SM, Chen KY, Brady SM, Broadney MM, Yanovski JA. Effects of colchicine in adults with metabolic syndrome: A pilot randomized controlled trial. Diabetes Obes Metab. 2019 Jul;21(7):1642-1651. doi: 10.1111/dom.13702. Epub 2019 Apr 2.
• Levine JA, Han JM, Wolska A, Wilson SR, Patel TP, Remaley AT, Periwal V, Yanovski JA, Demidowich AP. Associations of GlycA and high-sensitivity C-reactive protein with measures of lipolysis in adults with obesity. J Clin Lipidol. 2020 Sep-Oct;14(5):667-674. doi: 10.1016/j.jacl.2020.07.012. Epub 2020 Aug 4.
• Demidowich AP, Wolska A, Wilson SR, Levine JA, Sorokin AV, Brady SM, Remaley AT, Yanovski JA. Colchicine's effects on lipoprotein particle concentrations in adults with metabolic syndrome: A secondary analysis of a randomized controlled trial. J Clin Lipidol. 2019 Nov-Dec;13(6):1016-1022.e2. doi: 10.1016/j.jacl.2019.10.011. Epub 2019 Oct 22.
• Demidowich AP, Parikh VJ, Dedhia N, Branham RE, Madi SA, Marwitz SE, Roberson RB, Uhlman AJ, Levi NJ, Mi SJ, Jun JY, Broadney MM, Brady SM, Yanovski JA. Associations of the melanocortin 3 receptor C17A + G241A haplotype with body composition and inflammation in African-American adults. Ann Hum Genet. 2019 Sep;83(5):355-360. doi: 10.1111/ahg.12315. Epub 2019 Apr 2.

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