Colchicine's effect on aortic valve stenosis progression

Effect of Colchicine on the Progression of Aortic Valve Stenosis - a Pilot Study

This study is testing if colchicine can slow down the worsening of aortic valve stenosis in patients with mild to moderate cases compared to a placebo over six months.

Quick facts

• Phase: PHASE2; PHASE3
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ottawa Heart Institute Research Corporation (other)
• Drugs / interventions: methotrexate, prednisone
• Locations: 1 site (Ottawa, Ontario)
• Trial ID: NCT05253794 on ClinicalTrials.gov

What this trial studies

This pilot study investigates the impact of colchicine, an anti-inflammatory medication, on the progression of aortic valve stenosis by measuring valvular calcification activity through imaging techniques. It is a double-blinded, randomized trial comparing colchicine to a placebo over a 6-month period in patients with mild to moderate aortic stenosis. The primary endpoint is the change in 18F NaF uptake at the aortic valve, assessed using PET imaging. The study aims to enroll 24 patients, evenly divided between the two treatment arms.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with mild to moderate aortic stenosis defined by specific echocardiographic criteria.

Not a fit: Patients with severe aortic regurgitation, significant left ventricular dysfunction, or active inflammatory conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new therapeutic approach to slow the progression of aortic valve stenosis.

How similar studies have performed: While the use of colchicine for aortic stenosis is novel, similar anti-inflammatory approaches have shown promise in other cardiovascular conditions.

Eligibility criteria

Inclusion Criteria:

1. mild to moderate aortic stenosis defined by a mean pressure gradient using transthoracic echocardiography (TTE) between 15-25mmHg.
2. age greater than18 years;
3. given informed consent.

Exclusion Criteria:

1. bicuspid aortic valve
2. associated moderate to severe aortic regurgitation
3. associated other valvular pathology of moderate or greater severity
4. LV dysfunction (EF\<50%);
5. decompensated heart failure;
6. active infection (e.g. pneumonia, active skin infections, and on antibiotics);
7. chronic diarrhea;
8. immune compromise (e.g. recurrent infection);
9. history of cancer within the last 3 years (other than a successfully treated cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix).
10. active inflammatory conditions (e.g. rheumatoid arthritis, chronic inflammatory bowel disease, SLE, systemic anti-inflammatory therapy (e.g. prednisone, methotrexate));
11. pregnancy (all women of child bearing potential will have a negative BHCG test;
12. breastfeeding;
13. Women of childbearing potential who refuse to use two forms of contraception (this includes at least one form of highly effective and one effective method of contraception) throughout the study OR men capable of fathering a child who refuse to use contraception.
14. glomerular filtration rate (GFR) \<50 ml/min/1.72m2;
15. Use of p-glycoprotein inhibitor (e.g. cyclosporine, verapamil, or quinidine) or a strong CYP3A4 inhibitor (e.g. ritonavir, clarithromycin, or ketoconazole);
16. Hemoglobin \< 105(women) \<110 (men) g/L; WBC \< 3.0x 10(9)/L, platelet count\< 110x 10(9)/L;
17. Patient with a history of cirrhosis, chronic active hepatitis or severe hepatic disease or with alanine aminotransferase (ALT) levels greater than 3 times the upper limit of normal.
18. unable to give informed consent

Where this trial is running

Ottawa, Ontario

• University of Ottawa Heart Institute — Ottawa, Ontario, Canada (RECRUITING)

Study contacts

• Principal investigator: David [e-mail] — Ottawa Heart Institute Research Corporation
• Study coordinator: David Messika-Zeitoun

Conditions: Aortic Stenosis, Inflammation, colchicine