Colchicine to Suppress Inflammation and Improve Insulin Resistance in Adults and Adolescents With Obesity

NCT05017571 | Completed Phase 2 FDA Drug

• 2 other identifiers: 10000235000235-CH
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 1

Brief Summary

Background: 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. Objective: 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. Eligibility: 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. Design: Participants will be screened with the following: Medical history Physical exam Fasting blood tests Urine tests Electrocardiogram 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. ...

Conditions

Obesity; Insulin Resistance; Inflammation

Keywords

Diabetes; Overweight; comorbidities; Microbiome; C-Reactive Protein

Outcome Measures

Primary Outcomes (1)

• Change in Homeostatic model assessment of insulin resistance (HOMA-IR)

  HOMA-IR is calculated from fasting (f) insulin (I) and glucose (G): Gf (in mg/dL) x If in ( (Micro)IU/mL/ 405).

  From baseline to 3 months

Secondary Outcomes (4)

• Change in fasting serum insulin

  From baseline to 3 months

• Change in fasting serum glucose

  From baseline to 3 months

• Change in High-Sensitivity C-Reactive Protein

  From baseline to 3 months

• Change in Matsuda Index

  From baseline to 3 months

Study Arms (6)

Adults no obesity, insulin resistance, or inflammation

NO INTERVENTION

Adults without obesity, insulin resistance or inflammation

Adults with obesity, but no insulin resistance/inflammation

NO INTERVENTION

Adults with obesity, but without insulin resistance or inflammation

Colchicine - Adolescents

EXPERIMENTAL

Adolescents given Colchicine 0.6 mg per day (1 capsule per day)

Drug: Colchicine

Colchicine - Adults

EXPERIMENTAL

Adults given Colchicine 0.6 mg per day (1 capsule per day)

Drug: Colchicine

Placebo - Adolescents

PLACEBO COMPARATOR

Adolescents given Placebo (1 capsule per day)

Drug: Placebo

Placebo - Adults

PLACEBO COMPARATOR

Adults given Placebo (1 capsule per day)

Drug: Placebo

Interventions

Colchicine DRUG

Colchicine 1 capsule (0.6 mg) per day

Colchicine - Adolescents; Colchicine - Adults

Placebo DRUG

Placebo 1 capsule per day

Placebo - Adolescents; Placebo - Adults

Eligibility Criteria

• Age: 12 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All races/ethnicities and people of all genders are eligible to participate.
• Participants who will be randomized to colchicine or placebo must meet all of the following
• Age \>= 18y for adults; age 12y to \<18y for adolescents
• Obesity BMI \>= 30 kg/m2 (adults) or BMI \>= 95th percentile for age and sex per Centers for Disease Control Standards (adolescents)
• Weight \<= 450 lbs (204.5 kg) - due to DXA limitations
• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation.
• HOMA-IR \>= 2.6 mg/L, calculated as fasting glucose (in mg/dL) x insulin in (microIU/mL/ 405). Our goal is to enroll participants who have pre-existing insulin resistance.
• hsCRP \>= 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.
• Willing to be randomized (willing and able to give consent/assent as required for randomized study).
• Age \>= 18y
• BMI \>= 18 kg/m2
• Weight \<= 450 lbs (204.5 kg)
• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation
• Willing and able to provide consent for Evaluation-Only study

You may not qualify if:

• Individuals with significant medical comorbidities (e.g., NYHA Class III or IV heart failure, or CKD Stage 3b or worse (eGFR \< 60 mL/min/1.73 m2), or American Society of Anesthesiologists Physical Status Class 3 or above) or other serious disorders at the discretion of the investigators.
• HbA1c \> 7.0%
• Type 2 diabetes mellitus, as determined by either having:
• clear clinical diagnosis of diabetes, such as a patient in a hyperglycemic crisis or classic symptoms of hyperglycemia and a random plasma glucose \>= 200 mg/dL
• two of the following three:
• i. fasting plasma glucose \>= 126 mg/dL
• ii. Hemoglobin A1c \>= 6.5%
• iii. An oral glucose tolerance test glucose concentration of \>= 200 mg/dL at 2 hours.
• c. one of the above three criteria (bi.-biii.) meeting the T2DM cutoff on two different days.
• If only one of the above three criteria (bi.-biii.) meet the T2DM threshold during the Screening Visit, that test will be repeated on another day to determine if the subject has T2DM or not. As per ADA guidelines, The diagnosis \[of T2DM\] is made on the basis of the confirmed test.
• Moreover, because HbA1c has been shown to be higher in African Americans (AA) as compared to other races for the same glycemia, AA who do not have diabetes may be unfairly excluded by their HbA1c alone 96-98. Therefore, for AA subjects, if their fasting and 2h glucose is in the non-diabetes range, and the HbA1c is \< 7.0%, we will consider them not to have diabetes.
• Recent or regular use of colchicine, anorexiant, or diabetic medications in the last 3 months, or plan to start in the following 3 months.
• Recent or regular use of anti-inflammatory medications (e.g. prednisone, NSAIDs) in the last 7 days, or plan to start in the following 3 months.
• Current use of a strong or moderate CYP3A4 inhibitor or P-glycoprotein (P-gp), as this may cause a significant increase in colchicine plasma concentrations and risk for side effects. Oral contraceptive use will be permitted, provided the contraceptive has been used for at least two months before starting study medication. Note: HMA-CoA reductase inhibitors ( statins ) in adults only will also be
• Known allergy to colchicine.

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Demidowich AP, Davis AI, Dedhia N, Yanovski JA. Colchicine to decrease NLRP3-activated inflammation and improve obesity-related metabolic dysregulation. Med Hypotheses. 2016 Jul;92:67-73. doi: 10.1016/j.mehy.2016.04.039. Epub 2016 Apr 25.

  PMID: 27241260 BACKGROUND

• Demidowich AP, Levine JA, Apps R, Cheung FK, Chen J, Fantoni G; CHI Consortium; Patel TP, Yanovski JA. Colchicine's effects on metabolic and inflammatory molecules in adults with obesity and metabolic syndrome: results from a pilot randomized controlled trial. Int J Obes (Lond). 2020 Aug;44(8):1793-1799. doi: 10.1038/s41366-020-0598-3. Epub 2020 May 27.

  PMID: 32461554 BACKGROUND

• Demidowich AP, Levine JA, Onyekaba GI, Khan SM, Chen KY, Brady SM, Broadney MM, Yanovski JA. Effects of colchicine in adults with metabolic syndrome: A pilot randomized controlled trial. Diabetes Obes Metab. 2019 Jul;21(7):1642-1651. doi: 10.1111/dom.13702. Epub 2019 Apr 2.

  PMID: 30869182 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Obesity; Insulin Resistance; Inflammation; Diabetes Mellitus; Overweight

Interventions

Colchicine

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Pathologic Processes; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Study Officials

• Jack A Yanovski, M.D.

  Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2021
• First Posted: August 24, 2021
• Study Start: November 8, 2021
• Primary Completion: September 2, 2025
• Study Completion: September 2, 2025
• Last Updated: September 5, 2025

Record last verified: 2025-09-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Starting 6 months after the first study publication, IPD and supporting information will be shared and made available for 2 years by the PI.
• Access Criteria: Data will be shared for any analyses requested by an investigator with an affiliation to a research organization (e.g. a university) upon reasonable request to the Principal Investigator. A data sharing agreement must be concluded with NICHD and the request will be reviewed by the PI and the NICHD Clinical Director.

Locations

US (1)