Colchicine for Aortic Stenosis

(COPAS-Pilot Trial)

Overseen By David Messika-Zeitoun

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Ottawa Heart Institute Research Corporation

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

Disqualifiers: Cancer, Heart failure, Infections, 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: Unknown

Duration: 6 months

24 Participants Needed

What You Need to Know Before You Apply

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}

Who Is on the Research Team?

David [e-mail]

Principal Investigator

Ottawa Heart Institute Research Corporation

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Colchicine

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.

How Is the Trial Designed?

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

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?

Ottawa Heart Institute Research Corporation

Lead Sponsor

Trials

200

Recruited

95,800+

Published Research Related to This Trial

The crude aqueous extract of parsley significantly inhibits platelet aggregation in vitro and ex vivo, suggesting its potential as a natural anti-platelet agent, which could help in managing cardiovascular diseases.

Oral administration of parsley extract not only reduced platelet aggregation but also prolonged bleeding time in experimental animals, indicating its efficacy without affecting platelet count, likely due to its polyphenolic compounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parsley extract inhibits in vitro and ex vivo platelet aggregation and prolongs bleeding time in rats. Gadi, D., Bnouham, M., Aziz, M., et al.[2022]

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]

The aqueous extract of onion demonstrated significant antiplatelet effects in both rat and human platelets, with IC(50) values indicating effective inhibition of platelet aggregation induced by various agents, such as collagen and thrombin.

The mechanism of action includes reducing arachidonic acid release, inhibiting thromboxane A2 (TXA2) synthase activity, and blocking TXA2/PGH2 receptors, all without causing cytotoxic effects on platelets.

NCBI (Pubmed)

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. Moon, CH., Jung, YS., Kim, MH., et al.[2006]

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]

Citations

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]