Clinical trial NCT05253794: Effect of Colchicine on the Progression of Aortic Valve Stenosis - a Pilot Study
Official title: Effect of Colchicine on the Progression of Aortic Valve Stenosis - a Pilot Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Aortic Stenosis
Inflammation
Keywords: colchicine
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
First posted: 2022-02-24
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: COPAS pilot is a pilot single center double blinded randomized study to determine the effect of targeted anti-inflammation therapy using colchicine, on valvular calcification activity using imaging, i.e. aortic valvular NaF uptake. The current proposal uses a randomized design to evaluate the effect of colchicine vs. placebo on valvular calcification activity over 6 months measured using NaF PET

Detailed description: COPAS pilot is a pilot single center double blinded randomized study. The investigators will compare the effect of colchicine (0.6 mg daily - intervention arm) vs. placebo (control group) on the 18F NaF aortic valve uptake in patients with mild to moderate AS defined by a mean pressure gradient measured using transthoracic echocardiography (TTE) between 15-25 mm Hg after a 6-month period of treatment. The investigators plan to enroll 12 patients (6 males/6 females) in each arm (total sample size: 24 patients). Primary endpoint is the change in 18FNaF aortic valve uptake between baseline and 6 months in each arm. Parameters of interest are the maximal and total standard uptake values (SUVs) and tissue-to background ratios (TBRs) at the level of the aortic valve.

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

Primary outcomes:
measure: Change in aortic valve calcification activity
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
measure: Change in aortic valve calcification
timeFrame: One year
Locations:
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
Study officials:
affiliation: Ottawa Heart Institute Research Corporation
name: David Messika-Zetioun@ottawaheart.ca
role: PRINCIPAL_INVESTIGATOR
References: