Effects of Colchicine in Non-Diabetic Adults With Metabolic Syndrome
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|ClinicalTrials.gov Identifier: NCT02153983|
Recruitment Status : Completed
First Posted : June 3, 2014
Results First Posted : August 13, 2019
Last Update Posted : August 13, 2019
- 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 adults18 to 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.
|Condition or disease||Intervention/treatment||Phase|
|Obesity Metabolic Disease||Drug: Colchicine 0.6Mg Cap Drug: Placebo capsules given Drug: Colchicine 0.6Mg Tab||Phase 1 Phase 2|
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.
Seven 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||77 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Note that only 2 of the arms are randomized. Three arms are observational and one is open-label treatment.|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||In the randomized portion of the trial, all participants, Study Site staff, and pathology and laboratory personnel are blinded to the individual assignment of the order in which colchicine and placebo are administered.|
|Official Title:||Pilot Study of the Effects of Colchicine in Non-Diabetic Adults With Metabolic Syndrome|
|Study Start Date :||May 31, 2014|
|Actual Primary Completion Date :||August 15, 2018|
|Actual Study Completion Date :||August 15, 2018|
Experimental: Obese Adults with Metabolic Syndrome Randomized to Placebo
Experimental treatment with placebo capsules identical in appearance to the experimental colchicine preparation
Drug: Placebo capsules given
Placebo capsules given twice daily
Other Name: RCT Placebo
Experimental: Obese Adults with Metabolic Syndrome Randomized to Colchicine
Experimental treatment with colchicine capsules identical in appearance to the experimental placebo preparation
Drug: Colchicine 0.6Mg Cap
Colchicine 0.6 mg given twice daily
Other Name: RCT Colchicine
Experimental: Diet-controlled Type 2 Diabetes Adults Assigned to Colchicine
Participants with Diet-controlled Type 2 Diabetes who were assigned to Open-label treatment with colchicine. These participants were not randomized and were not part of the randomized controlled trial.
Drug: Colchicine 0.6Mg Tab
Other Name: Open-Label Colchicine 0.6 mg given twice daily
No Intervention: Evaluation Only Non-obese Adults
Participants without obesity seen only for the evaluation component of the study. Such participants are a control group for cross-sectional analyses of baseline data from the experimental cohort.
No Intervention: Evaluation Only Obese Adults Not Randomized
Participants with obesity seen only for the evaluation component of the study. Such participants are a control group for cross-sectional analyses of baseline data from the experimental cohort. These participants were found not eligible for randomization.
No Intervention: Evaluation Only Adults with Type 2 Diabetes
Participants with Diet-controlled Type 2 Diabetes seen only for the evaluation component of the study. Such participants are a control group for cross-sectional analyses of baseline data from the experimental cohort.
- Change in Insulin Sensitivity From FSIVGTT [ Time Frame: Baseline to 3 months ]Change (3 month minus minus baseline) in insulin sensitivity value, calculated from frequently-sampled intravenous glucose tolerance tests by Bergman's Minimal Model using intent-to-treat. Higher values represent a better outcome. There are no data from the evaluation-only participants, since they were not followed longitudinally.
- Change in HOMA-IR Index [ Time Frame: Baseline to 3 months ]Change (3 month minus minus baseline) in calculated homeostasis model of insulin sensitivity, calculated from derived from fasting glucose and insulin values = fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5) using intent-to-treat. Higher values represent a worse outcome. There are no data from the evaluation-only participants, since they were not followed longitudinally.
- Changes in C-reactive Protein [ Time Frame: Baseline to 3 months ]Change (3 month minus minus baseline) in High-Sensitivity C-reactive protein concentrations using intent-to-treat. Higher values represent a worse outcome. There are no data from the evaluation-only participants, since they were not followed longitudinally.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02153983
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Jack A Yanovski, M.D.||Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)|