Colchicine for Obesity and Insulin Resistance

Overseen By Jack A Yanovski, M.D.

Age: Any Age

Sex: Any

Trial Phase: Phase 2

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

Must not be taking: Colchicine, Anorexiants, Diabetic meds, NSAIDs

Disqualifiers: Heart failure, CKD, Diabetes, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the anti-inflammatory drug colchicine can improve metabolism in individuals with high body weight and insulin levels, but without high blood sugar. Researchers aim to determine if reducing inflammation can prevent future obesity-related health issues. Participants will be divided into groups, with some receiving colchicine and others a placebo, to compare outcomes. Individuals aged 12 or older, with high body weight and signs of increased inflammation, may be suitable for this trial. As a Phase 2 trial, this research measures colchicine's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial requires that participants generally take no medications, except for certain allowed ones like contraceptives, antihypertensives, and statins. Other medications will be reviewed individually, and you may need to stop taking some medications at least 3 months before joining the study.

Is there any evidence suggesting that colchicine is likely to be safe for humans?

Research has shown that colchicine is generally safe for people with obesity and metabolic syndrome. One study found that colchicine reduced inflammation related to obesity and was well-tolerated by adults. Other studies have reported similar findings, supporting its safety.

The FDA has approved colchicine for other uses, indicating it is usually safe when taken as directed. While some side effects may occur, they are often mild. Most participants in these studies reported good tolerance, which is encouraging for its use in this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for obesity?

Researchers are excited about colchicine as a treatment for obesity and insulin resistance because it offers a potentially new way to address inflammation, which is often linked to these conditions. Unlike standard treatments like lifestyle changes or medications targeting insulin levels directly, colchicine works by reducing inflammation at the cellular level. This anti-inflammatory action could help improve insulin sensitivity and aid weight management, offering a novel angle in tackling these health issues. Plus, colchicine is already well-known for treating gout, so its safety profile is familiar, making it a promising candidate for repurposing in metabolic conditions.

What evidence suggests that colchicine might be an effective treatment for obesity and insulin resistance?

Research has shown that colchicine, which participants in this trial may receive, can reduce inflammation and improve metabolism in people with obesity. One study found that colchicine significantly lowered markers of inflammation in adults with metabolic syndrome, potentially aiding insulin resistance. Insulin resistance occurs when the body doesn't use insulin properly, leading to high blood sugar. Another study demonstrated that colchicine could reduce insulin resistance, suggesting it might help control blood sugar levels. These findings offer promise for individuals with high body weight and increased inflammation. ^{1 2 3 4 6}

Who Is on the Research Team?

Jack A Yanovski, M.D.

Principal Investigator

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

Are You a Good Fit for This Trial?

This trial is for people aged 12 and older who are significantly overweight, with a BMI over 30 kg/m2 for adults or above the 95th percentile for children. They should have signs of inflammation (hsCRP >= 2.0 mg/L) and insulin resistance (HOMA-IR >= 2.6), but not diabetes (HbA1c <=7%). Women must use effective contraception if able to conceive.

Inclusion Criteria

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

I am at least 18 years old, or I am an adolescent aged 12 to 17.

My race, ethnicity, or gender does not exclude me from this trial.

Exclusion Criteria

You have major health problems or serious conditions, as decided by the researchers.

You have had a serious condition called agranulocytosis, gout, or significant myositis in the past.

I have had a condition where my lymphocytes multiply unusually.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline

Participants undergo baseline assessments including an Oral Glucose Tolerance Test (OGTT) and receive a 12-week supply of the study drug or placebo

1 day

1 visit (in-person)

Treatment

Participants take the study drug or placebo daily for 12 weeks, with study visits at 6 weeks and 12 weeks

12 weeks

2 visits (in-person), 3 phone check-ins

Follow-up

Participants are monitored for safety and effectiveness after treatment, including repeat OGTT at the 12-week visit

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Colchicine
• Placebo

Trial Overview Researchers are testing whether colchicine, an anti-inflammatory medication, can improve metabolism in obese individuals with high levels of inflammation and insulin without high blood sugar yet. Participants will take either colchicine or a placebo daily for up to four months, including check-ins and tests like OGTT.

How Is the Trial Designed?

Group I: Colchicine - Adults Experimental Treatment 1 Intervention

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

Group II: Colchicine - Adolescents Experimental Treatment 1 Intervention

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

Group III: Adults no obesity, insulin resistance, or inflammation Active Control 1 Intervention

Adults without obesity, insulin resistance or inflammation

Group IV: Adults with obesity, but no insulin resistance/inflammation Active Control 1 Intervention

Adults with obesity, but without insulin resistance or inflammation

Group V: Placebo - Adolescents Placebo Group 1 Intervention

Adolescents given Placebo (1 capsule per day)

Group VI: Placebo - Adults Placebo Group 1 Intervention

Adults given Placebo (1 capsule per day)

Colchicine is already approved in United States for the following indications:

Approved in United States as Colcrys for:

• Gout
• Familial Mediterranean Fever

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

A 27-year-old man with acanthosis nigricans (AN) showed significant improvement in his condition after following a very low-calorie diet, which also helped reduce his weight and insulin resistance.

The results suggest that insulin resistance is a primary factor contributing to AN, rather than hypothyroidism, as the improvement in AN occurred before the correction of his thyroid condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acanthosis nigricans with severe obesity, insulin resistance and hypothyroidism: improvement by diet control. Kuroki, R., Sadamoto, Y., Imamura, M., et al.[2017]

In a 12-week pilot study involving 7 overweight or obese subjects with acanthosis nigricans, only rosiglitazone significantly reduced insulin levels, suggesting a potential metabolic benefit.

Both metformin and rosiglitazone were well-tolerated, but neither showed a significant effect on the severity of acanthosis nigricans lesions, indicating that longer treatment periods may be necessary to observe more substantial improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of metformin versus rosiglitazone in patients with Acanthosis nigricans: a pilot study. Bellot-Rojas, P., Posadas-Sanchez, R., Caracas-Portilla, N., et al.[2022]

In a study of 70 patients with acanthosis nigricans (AN) and acrochordon, 41.4% showed insulin resistance (IR), significantly higher than the 17.1% in the control group, indicating a strong association between these skin conditions and IR.

The mean HOMA-IR value was also significantly higher in patients with AN and acrochordon (4.32) compared to controls (2.27), suggesting that these skin markers may be useful indicators of underlying insulin resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Acanthosis Nigricans and Acrochordon with Insulin Resistance: A Cross-Sectional Hospital-Based Study from North India. Singh, SK., Agrawal, NK., Vishwakarma, AK.[2022]

In a study of 11 morbidly obese patients undergoing gastric bypass surgery, significant weight loss led to an 84% decrease in fasting insulin levels and a 360% increase in insulin sensitivity, indicating improved insulin action after weight loss.

The reduction in specific long-chain fatty acyl-CoAs (like palmityl CoA and stearate CoA) in muscle tissue suggests that lowering intramyocellular fatty acyl-CoA levels may contribute to the enhanced insulin sensitivity observed post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of weight loss on insulin sensitivity and intramuscular long-chain fatty acyl-CoAs in morbidly obese subjects. Houmard, JA., Tanner, CJ., Yu, C., et al.[2019]

Acanthosis nigricans and acrochordons are skin conditions that can serve as visible indicators of insulin resistance, making them important for early diagnosis.

Recognizing these skin signs can lead to timely treatment, which is crucial in preventing complications associated with insulin resistance and non-insulin-dependent diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of acanthosis nigricans and skin tags with insulin resistance. Barbato, MT., Criado, PR., Silva, AK., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6570563/

Effects of Colchicine in Adults with Metabolic Syndrome This pilot study found colchicine significantly improved obesity-associated inflammatory variables and demonstrated a good safety profile among adults with ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05017571

Colchicine to Suppress Inflammation and Improve Insulin ... This study will determine the effects of colchicine on insulin resistance and beta cell reserve in adults with obesity

3. mdpi.com mdpi.com/2218-1989/14/11/629

The Action of Colchicine in Patients with Metabolic ... The results of the primary and secondary analyses revealed that colchicine was able to reduce inflammation and insulin resistance, improve ...

4. nature.com nature.com/articles/s41366-020-0598-3

Colchicine's effects on metabolic and inflammatory ... The primary outcome was change in insulin sensitivity. The study protocol was approved by the Eunice Kennedy Shriver National Institute of ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6554767/

OR31-2 Effects of Colchicine on Insulin Resistance ... Data were analyzed according to intention-to-treat and reported as mean±SD. Results: Colchicine significantly reduced inflammatory indices, including hsCRP (- ...

6. ahajournals.org ahajournals.org/doi/10.1161/ATVBAHA.124.319851

Colchicine's Role in Cardiovascular Disease Management The aforementioned landmark clinical trials also provide the largest randomized safety data for low-dose colchicine. In LoDoCo2, 437 ...