Effects of Colchicine in Non-Diabetic Adults With Metabolic Syndrome
Condition: Obesity; Metabolic Disease
MeSH terms: Metabolic Syndrome; Metabolic Diseases
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Detailed description: 
      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.
    

Intervention name(s): Colchicine 0.6Mg Cap; Placebo capsules given; Colchicine 0.6Mg Tab
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Colchicine 0.6 mg given twice daily; Placebo capsules given twice daily; Open-label colchicine
Other intervention name(s): RCT Colchicine; RCT Placebo; Open-Label Colchicine 0.6 mg given twice daily
Intervention MeSH terms: Colchicine
Allocation: Randomized
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)
Primary purpose: Treatment
Keywords: Obesity; Colchicine; Inflammation; Metabolic Syndrome; Dyslipidemia