Colchicine for Aortic Stenosis

(COPAS-Pilot Trial)

Overseen by David [e-mail]

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Ottawa Heart Institute Research Corporation

Must not be taking: Antibiotics, Prednisone, Methotrexate, others

Disqualifiers: Cancer, Heart failure, Infections, others

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial tests if colchicine, an anti-inflammatory drug, can reduce calcium buildup in the heart valves of patients with mild to moderate aortic stenosis. The study will test colchicine over several months to see if it helps reduce valve hardening. Colchicine has shown modest benefits in early nonsevere COVID-19 but is associated with common adverse effects.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using certain medications like p-glycoprotein inhibitors or strong CYP3A4 inhibitors.

How does the drug colchicine differ from other treatments for aortic stenosis?

Colchicine is unique for aortic stenosis as it is primarily an anti-inflammatory drug, traditionally used for conditions like gout, and it may offer a novel approach by targeting inflammation, unlike standard treatments that focus on mechanical relief of the narrowed aortic valve. ^{1 2 3 4 5}

Research Team

David [e-mail]

Principal Investigator

Ottawa Heart Institute Research Corporation

Eligibility Criteria

Adults over 18 with mild to moderate aortic stenosis (15-25mmHg pressure gradient) can join this study. They must be able to consent and agree to use two forms of contraception if capable of childbearing. Excluded are those with severe heart issues, liver disease, immune compromise, certain medication use, recent cancer (except some skin cancers), pregnancy, breastfeeding or poor kidney function.

Inclusion Criteria

My heart valve narrowing is mild to moderate.

I am older than 18 years.

Given informed consent

Exclusion Criteria

Breastfeeding

I am not taking medications like cyclosporine, verapamil, or ketoconazole.

I have moderate or severe heart valve problems.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive colchicine or placebo daily for 6 months to assess the effect on aortic valve calcification

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Colchicine (Anti-inflammatory)

Trial Overview The COPAS pilot is testing whether Colchicine can slow down the hardening of the aortic valve by comparing it against a placebo. Participants will be randomly assigned to one of these two groups in a double-blind manner and monitored for 6 months using NaF PET imaging.

Participant Groups

Group I: Colchicine Experimental Treatment 1 Intervention

Colchicine 0.6mg PO daily for 6 months

Group II: Placebo Placebo Group 1 Intervention

Placebo tablet daily for 6 months

Who Is Running the Clinical Trial?

Ottawa Heart Institute Research Corporation

Lead Sponsor

Trials

200

Recruited

95,800+

Dr. Thierry Mesana

Ottawa Heart Institute Research Corporation

Chief Medical Officer since 2014

MD from McGill University

Dr. Rob Beanlands

Ottawa Heart Institute Research Corporation

Chief Executive Officer since 2024

MD from the University of Ottawa

Findings from Research

A new compound, 1,7-bis(4-hydroxyphenyl)-3-hydroxy-1,3-heptadien-5-one, isolated from Alpinia blepharocalyx seeds, demonstrated strong inhibition of platelet aggregation in human blood, suggesting potential as an antiplatelet agent.

Another compound, identified as compound 3, also effectively inhibited various forms of platelet aggregation, indicating that these compounds could be valuable in developing treatments for conditions related to excessive blood clotting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new antiplatelet diarylheptanoid from Alpinia blepharocalyx. Doug, H., Chen, SX., Xu, HX., et al.[2014]

Garlic powder, tomato extract, and their mixture were found to have anti-thrombotic effects in a rat model, as they delayed blood clotting times and reduced certain inflammatory markers after 7 days of treatment.

Histological analysis indicated that these treatments improved thrombosis conditions in the aorta and lungs, although combining garlic and tomato extract did not enhance the effects compared to using them individually.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative study of the antithrombotic effect through activated endothelium of garlic powder and tomato extracts using a rodent model of collagen and epinephrine induced thrombosis. Kim, L., Lim, Y., Park, SY., et al.[2020]

A meta-analysis of 11 trials with 477 participants found that Ginkgo biloba extract did not provide a clinically significant improvement in walking distance for patients with intermittent claudication, showing only a marginal increase of 64.5 meters compared to placebo.

Despite being a vasoactive agent used for symptom relief, the results suggest that Ginkgo biloba may not be an effective treatment option for enhancing walking capacity in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From the Cochrane library: Ginkgo biloba for intermittent claudication. Nicolaï, SP., Gerardu, VC., Kruidenier, LM., et al.[2012]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Parsley extract inhibits in vitro and ex vivo platelet aggregation and prolongs bleeding time in rats. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

A new antiplatelet diarylheptanoid from Alpinia blepharocalyx. [2014]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

A comparative study of the antithrombotic effect through activated endothelium of garlic powder and tomato extracts using a rodent model of collagen and epinephrine induced thrombosis. [2020]

4. Scotland pubmed.ncbi.nlm.nih.gov

Mechanism for antiplatelet effect of onion: AA release inhibition, thromboxane A(2)synthase inhibition and TXA(2)/PGH(2)receptor blockade. [2006]

5. Switzerland pubmed.ncbi.nlm.nih.gov

From the Cochrane library: Ginkgo biloba for intermittent claudication. [2012]