Colchicine to Suppress Inflammation and Improve Insulin Resistance in Adults and Adolescents With Obesity
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|ClinicalTrials.gov Identifier: NCT05017571|
Recruitment Status : Recruiting
First Posted : August 24, 2021
Last Update Posted : November 19, 2021
About 40 percent of adults and 20 percent of adolescents in the U.S. have a body mass index over 30 kg/m2. Being overweight may lead to a state of low-level inflammation. This may cause health problems. Researchers want to see if an anti-inflammatory medicine can help.
To learn if colchicine can improve metabolism in people who have high body weight, increased inflammation, and high insulin in the blood but who have not yet developed high blood sugar.
People aged 12 and older with high body weight who may have increased inflammation and high insulin in the blood. Healthy adult volunteers are also needed.
Participants will be screened with the following:
Fasting blood tests
Dual energy x-ray absorptiometry (They will lie on a table while a camera passes over their body.)
Stool sample and 24-hour food diary (optional)
Participants will have 3 study visits and 3 phone check-ins. At visits, they will repeat some screening tests.
Healthy volunteers will have the baseline visit only. They will not get the study drug.
At the baseline visit, participants will have an Oral Glucose Tolerance Test (OGTT). For this, they will drink a sweet liquid and then give blood samples. They will get a 12-week supply of the study drug or placebo to take daily by mouth.
Participants will have study visits 6 weeks and 12 weeks after they started taking the study drug. At the 12-week visit, they will repeat the OGTT.
Participation will last for 3 (Omega) to 4 months.
|Condition or disease||Intervention/treatment||Phase|
|Obesity Insulin Resistance Inflammation||Drug: Colchicine Drug: Placebo||Phase 2|
Obesity affects more than 40% of the adult U.S. population plus approximately 20% of adolescents 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 when circulating molecules such as fatty acids and cholesterol crystals bind to nucleotide-binding oligomerization (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) receptors. 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 that is approved for use in the treatment of gout and some rare inflammatory conditions in adults and children, disrupts intracellular NLRP3 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 versus placebo once daily in non-diabetic adults and adolescents with obesity, insulin resistance, and inflammation (elevated high-sensitivity C-reactive protein concentrations). From among up to 500 individuals screened, we will conduct a randomized, double-blinded, placebo-controlled trial of colchicine in up to 200 adults. We will also obtain pilot data from 40 adolescents studied in the same randomized fashion. This study will determine the effects of colchicine on insulin resistance and beta cell reserve in adults with obesity and allow determination of the sample size needed to conduct an adequately powered study of the effects of colchicine in adolescents. An Evaluation-Only control group of up to 50 adults who do not meet entry criteria for the randomized clinical trial will also be studied with baseline tests only.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||500 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||COLSIO Trial: Phase II Randomized, Controlled Trial of Colchicine to Suppress Inflammation and Improve Insulin Resistance in Adults and Adolescents With Obesity|
|Actual Study Start Date :||November 8, 2021|
|Estimated Primary Completion Date :||October 1, 2024|
|Estimated Study Completion Date :||October 1, 2025|
No Intervention: Adults no obesity, insulin resistance, or inflammation
Adults without obesity, insulin resistance or inflammation
No Intervention: Adults with obesity, but no insulin resistance/inflammation
Adults with obesity, but without insulin resistance or inflammation
Experimental: Colchicine - Adolescents
Adolescents given Colchicine 0.6 mg per day (1 capsule per day)
Colchicine 1 capsule (0.6 mg) per day
Experimental: Colchicine - Adults
Adults given Colchicine 0.6 mg per day (1 capsule per day)
Colchicine 1 capsule (0.6 mg) per day
Placebo Comparator: Placebo - Adolescents
Adolescents given Placebo (1 capsule per day)
Placebo 1 capsule per day
Placebo Comparator: Placebo - Adults
Adults given Placebo (1 capsule per day)
Placebo 1 capsule per day
- Change in Homeostatic model assessment of insulin resistance (HOMA-IR) [ Time Frame: From baseline to 3 months ]HOMA-IR is calculated from fasting (f) insulin (I) and glucose (G): Gf (in mg/dL) x If in ( (Micro)IU/mL/ 405).
- Change in fasting serum insulin [ Time Frame: From baseline to 3 months ]Fasting serum insulin
- Change in fasting serum glucose [ Time Frame: From baseline to 3 months ]Fasting serum glucose
- Change in High-Sensitivity C-Reactive Protein [ Time Frame: From baseline to 3 months ]High-Sensitivity C-Reactive Protein
- Change in Matsuda Index [ Time Frame: From baseline to 3 months ](10^4/([Gf x 18] x If x [mean GOSTTx18] x mean I-OSTT)0.5), where Gf is fasting glucose, If is fasting insulin, and I-OSTT is mean insulin from oral sugar tolerance test
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): NCT05017571
|Contact: Sheila M Brady, C.R.N.P.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Jack A Yanovski, M.D.||Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)|