Canagliflozin Targeting Vascular Inflammation

Coronary Artery Disease Clinical Trial

— CANTORSING  

Official title:

Canagliflozin Targeting Vascular Inflammation: An Ottawa Imaging Study - A Pilot Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05427084
• Other study ID #: 20220176-01H
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: May 2024
• Est. completion date: December 2025

Study information

• Verified date: April 2024
• Source: Ottawa Heart Institute Research Corporation
• Contact: Kevin Boczar, MD
• Phone: 613 696 7000
• Email: kboczar[@]ottawaheart.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

CANTOR SING is a pilot single center double blinded randomized study. The investigators will compare the effect of canagliflozin (300 mg daily - intervention arm) vs. placebo (control group) on the FDG aortic uptake in patients with stable CAD (over 60 days post-myocardial infarction) after a 6-month period of treatment. The investigators plan to enroll 8 patients in each arm (total sample size: 16 patients). Primary endpoint is the change in FDG aortic uptake between baseline and 6 months in each arm.

Description:

CANTOR SING is a pilot single center double blinded randomized study to determine the effect of targeted anti-inflammation therapy using canagliflozin, on aortic inflammation using imaging, i.e. ascending aortic FDG uptake. The current proposal uses a randomized design to evaluate the effect of canagliflozin vs. placebo on aortic inflammation activity over 6 months measured using FDG PET. At the University of Ottawa Heart Institute (UOHI) patients with diabetes and stable CAD (defined as patients over 60 days post-myocardial infarction) will be recruited. Patients who meet inclusion/exclusion criteria will undergo clinical evaluation, FDG PET imaging with contrast-CT, and blood sample collection. HbA1C, Fasting Blood Sugar (FBS), lipids, C-reactive protein (CRP), creatinine (CR), glomerular filtration rate (GFR), complete blood count (CBC), hemoglobin, liver function tests - AST, ALT, creatine kinase (CK) will be collected from the patient's clinical data or if not available may be collected as part of the study. Patients recruited into the CANTOR SING study will be randomized to receive either an oral canagliflozin 300 mg capsule or placebo capsule administered once daily for 6 months. Patients will take the medication for 6 months. The study will be conducted in a double-blinded fashion. Patients will be followed up every 3 months for the 6-month evaluation period. Clinical evaluation and blood collection for labs (CBC, electrolytes, CPK, ALT, AST, creatinine) will performed at baseline and will be repeated every 3 months for a a total of 6 months of follow-up. FDG PET imaging with contrast-CT will be repeated at 6 months. Finally, blood will be collected at baseline and 6 months.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 24
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 1) Stable CAD (over 60 days post-myocardial infarction).
• 2) Diabetes
• 3) given informed consent.

Exclusion Criteria:

1. severe LV dysfunction (EF<50%);

2. decompensated heart failure;

3. active infection (e.g. pneumonia, active skin infections, and on antibiotics);

4. active inflammatory conditions (e.g. rheumatoid arthritis, chronic inflammatory bowel disease, SLE, systemic anti-inflammatory therapy (e.g. prednisone, methotrexate));

5. pregnancy (all women of child bearing potential will have a negative BHCG test;

6. breastfeeding;

7. 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.

8. glomerular filtration rate (GFR) <50 ml/min/1.72m2;

9. Use of p-glycoprotein inhibitor (e.g. cyclosporine, verapamil, or quinidine) or a strong CYP3A4 inhibitor (e.g. ritonavir, clarithromycin, or ketoconazole);

10. Hemoglobin < 105(women) <110 (men) g/L; WBC < 3.0x 10(9)/L, platelet count< 110x 10(9)/L;

11. 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.

12. unable to give informed consent;

Related Conditions & MeSH terms

• Coronary Artery Disease
• Diabetes Mellitus, Type 2
• Diabetes Type 2
• Inflammation

Intervention

Drug:
• Canagliflozin
Canagliflozin tablet 300mg PO daily
• Placebo
Placebo tablet

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
Primary	TBR (Tissue-to-blood ratio) of the most-diseased segment (MDS) of the ascending aorta	TBR (Tissue-to-blood ratio) is a marker of arterial plaque inflammation. It will be measured in the maximum disease segment (MDS)(the segment with the highest FDG uptake at baseline) in the aorta	6 months
Secondary	Change in inflammatory biomarkers	The investigators will measure inflammatory biomarkers (hsCRP, IL-6, IL-7, IL-8, MCP) at baseline and on study completion (pg/mL)	6 months
Secondary	Change in monocyte marker expression	Change in monocyte marker expression (% positive cells) of CD14++CD16-, CD14++CD16+, CD14+CD16+, CD14+CD16-, CD127, and CCR2 from baseline to follow-up	6 months