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

Inflammation Clinical Trial

— COPAS-Pilot  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05253794
• Other study ID #: 20210526
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: July 1, 2022
• Est. completion date: September 30, 2024

Study information

• Verified date: August 2023
• Source: Ottawa Heart Institute Research Corporation
• Contact: David Messika-Zeitoun
• Phone: 613 796 7000
• Email: DMessika-zeitoun[@]ottawaheart.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: September 30, 2024
• Est. primary completion date: May 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aortic Stenosis
• Aortic Valve Stenosis
• Constriction, Pathologic
• Inflammation

Intervention

Drug:
• Colchicine 0.6 mg
oral tablet daily for 6 months
• Placebo
oral tablet daily for 6 months

Locations

Country	Name	City	State
Canada	University of Ottawa Heart Institute	Ottawa	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Ottawa Heart Institute Research Corporation

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in aortic valve calcification	Change is the degree of aortic valve calcification measured using CT scan (calcium score) and expressed in arbitrary units	One year
Primary	Change in aortic valve calcification activity	Change in valvular calcification activity as measured by NaF uptake by Target to Background Ratio (TBR) on PET/CT imaging	6 months