Trial record 27 of 47 for:    diabetes | NICHD [Lead] | NIH

Effects of Colchicine in Non-Diabetic Adults With Metabolic Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Collaborators:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
ClinicalTrials.gov Identifier:
NCT02153983
First received: May 31, 2014
Last updated: June 4, 2014
Last verified: April 2014
  Purpose

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 adults at least 18 years old.

Design:

  • Participants must fast before each visit, including the screening visit.
  • Participants will be screened with blood tests, stool sample, 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, and give a stool sample.
  • 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, medical history, and physical exam. They will give a stool sample.
  • For visit 3, participants will repeat the tests in visit 1.

Condition Intervention Phase
Obesity
Metabolic Disease
Drug: Colchicine 0.6 mg given
Drug: Placebo capsules given
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Change in insulin sensitivity [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 100
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)
Arms Assigned Interventions
Experimental: Colchicine
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

Subjects will qualify for inclusion if they meet the following criteria:

  • Good general health. In general subjects should take no medications. However, individuals taking medications for obesity-related co-morbid conditions, who have not had changes in dosage for more than 6 months, may be included, at the discretion of the principal investigator.
  • Obesity, defined as a body mass index (BMI) (Bullet) 30 kg/m2, but weight less than 450 lbs in order for subjects to undergo Dual-Energy X-ray Absorptiometry (DXA) scanning.
  • Age greater than or equal to 18 years.
  • Metabolic Syndrome, as per NCEP/ATPIII Guidelines

    --(Any 3 of the following 5):

    • FPG greater than or equal to 100 mg/dl, or on treatment
    • Triglycerides greater than or equal to 150 mg/dl, or on treatment
    • Waist Circumference: Men greater than or equal to 40 in (greater than or equal to 102 cm); Women greater than or equal to 35 in (greater than or equal to 88 cm)
    • Reduced HDL-C: Men < 40 mg/dl; Women < 50 mg/dl, or on treatment
    • Hypertension: greater than or equal to 130 mmHg systolic, or greater than or equal to 85 mmHg diastolic, or on treatment
  • HOMA-IR greater than or equal to 2.6. Our goal is to enroll participants who have pre-existing insulin resistance.
  • hsCRP greater than or equal to 2.0 mg/L. We aim to recruit participants with increased baseline level of inflammation. Individuals with hsCRP above 2.0 mg/L have been shown to have an increased risk for cardiovascular events.

EXCLUSION CRITERIA:

For subjects and controls:

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  • Type 2 diabetes mellitus, as determined by a fasting plasma glucose greater than or equal to 126 mg/dL, hemoglobin A1c greater than or equal to 6.5%, or an oral glucose tolerance test glucose concentration of greater than or equal to 200 mg/dL at 2 hours.
  • Presence of a significant active or chronic illness likely to limit life span and/or increase risk of intervention, including renal (GFR less than or equal to 60 ml/min/1.73m(2)), cardiovascular, hepatic (other than obesity-related steatosis), gastrointestinal, immunologic, endocrinologic (e.g. Cushing syndrome), pulmonary (other than either asthma not requiring continuous medication or sleep apnea-related disorders), or other disorders at the discretion of the investigators.
  • Recent use of colchicine or anorexiant medications in the last 3 months.
  • Known allergy to colchicine.
  • Previous history of agranulocytosis, gout, or significant myositis.
  • Females who are pregnant, planning to become pregnant, currently nursing an infant, or have irregular menses, defined as cycles less than 21 days or greater than 45 days.
  • Individuals who have current substance abuse or a psychiatric disorder or any other condition that in the opinion of the investigators would impede competence, compliance, or participation in the study.
  • Subjects who regularly use prescription medications unrelated to the complications of obesity, especially those known to affect enzymes involved in colchicine metabolism, such as CYP3A4 or P-glycoprotein (P-gp). Oral contraceptive use will be permitted, provided the contraceptive has been used for at least two months before starting study medication. The use of over-the-counter and prescription medications will be reviewed on a case-by-case basis; depending on the medication, subjects who have continued to take prescription medication for at least 3 months prior to study entry may be eligible.
  • Participation in a formal weight loss program (e.g. Weight Watchers) or recent weight change of more than 3% of body weight in the past two months.
  • Use of anti-inflammatory medications (e.g. prednisone, NSAIDs) chronically or in the last 7 days prior to fat biopsy.
  • History of keloid formation.
  • Current users of tobacco products.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02153983

Contacts
Contact: Andrew P Demidowich, M.D. (301) 594-1176 demidowicha@mail.nih.gov
Contact: Jack A Yanovski, M.D. (301) 496-0858 jy15i@nih.gov

Locations
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    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Jack A Yanovski, M.D. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
ClinicalTrials.gov Identifier: NCT02153983     History of Changes
Other Study ID Numbers: 140119, 14-CH-0119
Study First Received: May 31, 2014
Last Updated: June 4, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Obesity
Colchicine
Inflammation
Metabolic Syndrome
Dyslipidemia

Additional relevant MeSH terms:
Metabolic Diseases
Obesity
Metabolic Syndrome X
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Colchicine
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 19, 2014