Effects of Colchicine in Non-Diabetic Adults With Metabolic Syndrome
- 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.
- To learn whether colchicine improves sugar regulation and metabolism.
- Healthy overweight adults at least 18to 100 years old.
- 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.
Drug: Colchicine 0.6 mg given
Drug: Placebo capsules given
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Pilot Study of the Effects of Colchicine in Non-Diabetic Adults With Metabolic Syndrome|
- Change in insulin sensitivity [ Time Frame: 3 months ] [ Designated as safety issue: No ]
- Change in metabolic parameters [ Time Frame: 3 months ] [ Designated as safety issue: No ]
- Changes in other inflammatory markers [ Time Frame: 3 months ] [ Designated as safety issue: No ]
|Study Start Date:||May 2014|
|Estimated Study Completion Date:||December 2018|
|Estimated Primary Completion Date:||June 2018 (Final data collection date for primary outcome measure)|
Experimental treatment with colchicine
Drug: Colchicine 0.6 mg given
Colchicine 0.6 mg given twice daily
Placebo Comparator: Drug
Placebo capsules identical to
Drug: Placebo capsules given
Placebo capsules given twice daily
Obesity affects one-third of the adult U.S. population and is a major risk factor for the development of type 2 diabetes and cardiovascular disease. Mouse models and human data suggest that obesity-induced chronic inflammation is one mechanism promoting obesity-associated comorbid conditions. In obesity, innate immunity is activated by circulating molecules such as fatty acids and cholesterol crystals bind to nucleotide-binding oligomerization (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) receptors in adipocyte tissue macrophages (ATMs). This binding stimulates NLRP3 oligomerization, inflammasome formation, and proinflammatory cytokine activation. The resultant inflammatory cascade leads to insulin resistance and decreased pancreatic beta-cell reserve. It has been proposed that the suppression of this chronic low-level inflammatory state may impede the onset of diabetes and cardiovascular disease.
Recent studies have shown colchicine, a potent microtubule inhibitor commonly used for the treatment of gout and some rare inflammatory conditions, disrupts intracellular localization of NLRP3, thereby blocking inflammasome assembly. As there are limited medical therapies proven effective to improve obesity-related metabolic dysregulation, we propose to determine the efficacy of colchicine 0.6 mg twice daily in non-diabetic obese adults with metabolic syndrome. We will conduct a randomized, double-blinded, placebo-controlled pilot trial of colchicine in forty subjects. We will study changes in insulin resistance, beta-cell reserve, and systemic inflammation. Using adipose tissue obtained from biopsies, we will also study colchicine s local effects on inflammation and insulin resistance. Should results prove promising, this pilot study will allow determination of the sample size needed for an adequately powered study of the effects of colchicine in obese adults with metabolic syndrome.
5 patients with diet-controlled type 2 diabetes will be given open-label colchicine and followed as described above. We also plan to perform baseline evaluations on 40 subjects who are not eligible for the treatment protocol. This group will consist of non-obese adults, obese adults who are not insulin-resistant, and adults with diet-controlled type 2 diabetes.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02153983
|Contact: Andrew P Demidowich, M.D.||(301) firstname.lastname@example.org|
|Contact: Jack A Yanovski, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Jack A Yanovski, M.D.||Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)|