Colchicine in Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction

Colchicine Clinical Trial

Official title:

Colchicine in Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05637398
• Other study ID #: 03-22
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 15, 2022
• Est. completion date: November 1, 2024

Study information

• Verified date: August 2022
• Source: I.M. Sechenov First Moscow State Medical University
• Contact: Anastasia SHCHENDRYGINA
• Phone: +79262309207
• Email: a.shchendrygina[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Heart failure with preserved left ventricular ejection fraction (HFpEF) is a syndrome associated with high morbidity and mortality rates. Systemic low-grade inflammation is acknowledged to be a fundamental pathophysiological mechanism of HFpEF. Interventions targeting inflammatory pathway is understudied in HFpEF. Colchicine is a safe and well tolerated anti-inflammatory drug, which interferes with several steps in the inflammatory process. The drug has been extensively studied in different cardiovascular pathologies except HFpEF. We assume that colchicine decreases inflammation and reduces sST2 levels in HFpEF.

Description:

HFpEF is a syndrome associated with high morbidity and mortality rates. The underlying mechanisms of the syndrome are not fully understood. Systemic low-grade inflammation is acknowledged to be a fundamental pathophysiological mechanism of HFpEF, which facilitates cardiomyocyte stiffness and myocardial fibrosis development. However, anti-inflammatory treatment approaches are largely under studied. Colchicine is a safe and well tolerated anti-inflammatory drug, which interferes with several steps in the inflammatory process, resulting in suppression of a number of pro-inflammatory pathways and cytokines release, including IL-1, hsCRP. The drug has been extensively studied in patients with coronary artery disease (COLCOT, LoDoCo2) and showed significant reduction in risk of cardio-vascular events, as well as inflammation. Post-hoc analysis of in the CANTOS study investigated the effect of monoclonal antibody targeting interleukin-1β in patients with prior myocardial infarction, showed a reduction in heart failure (HF) hospitalization of patients with elevations in high-sensitivity C-reactive protein (hsCRP). There is no data available regarding the effect of Colchicine on HFpEF patients. Soluble suppression of tumourigenicity 2 (sST2), a member of the interleukin (IL)-1 receptor family, which is not restricted to inflammation, but is also expressed in cardiomyocytes, fibroblast and endothelial cells of cardiac microvessels in response to myocardial stress antagonizing cardioprotective effects of IL-33/ST2 system. In HFpEF, sST2 associated with worse clinical signs and symptoms, co-morbidities, biomarkers of fibrosis and neurohormonal activation. Elevated levels of sST2 are acknowledged as a predictor of worse prognosis in both HF with reduced ejection fraction (HFrEF) and HFpEF. We assume that colchicine decreases inflammation and reduces sST2 levels in HFpEF.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: November 1, 2024
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

• 40 years of age, male and female

• Left ventricular ejection fraction (LVEF) = 50%

• Symptoms and signs of heart failure

• N-terminal pro-B-type natriuretic peptide (NT-proBNP) =300 pg/ml at baseline (patients in atrial fibrillation at baseline NT-proBNP = 600 pg/ml), left atrial volume index (LAVI) >34 mL/m2 or a left ventricular mass index (LVMI) =115 g/m2 for males and =95 g/m2 for females

• body mass index (BMI) > 30kg/m2 or diabetes mellitus

Exclusion Criteria:

• Hypertrophic cardiomyopathy, constrictive pericarditis, or cardiac amyloidosis

• Acute decompensation of HF in the last 1 month

• Valvular heart disease

• Prior history of LVEF below 50%

• Acute myocardial infarction in the last 3 months, cardiac surgery or cerebrovascular accident within the recent 6 months

• Any active or chronic inflammatory diseases or infections

• Patients with indication for colchicine therapy or history of colchicine intolerance

• Severe hepatic (alanine aminotransferase N3 upper limit of normal or renal dysfunction (estimated glomerular filtration rate <45 mL/min per 1.73m2)

• Severe nervous system diseases

• History of any malignancy or suffering from cancer

• Lack of informed consent

Related Conditions & MeSH terms

• Colchicine
• Heart Failure

Intervention

Drug:
• Colchicine
The active treatment intervention consists of colchicine 0.5 mg twice daily that will be administrated by the investigator

Locations

Country	Name	City	State
Russian Federation	A Shchendrygina	Moscow
Russian Federation	Anastasia Shchendrygina	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
I.M. Sechenov First Moscow State Medical University

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Soluble suppression of tumourigenicity 2 (sST2,ng/ml)	Delta_circulating sST2	from baseline to 12 weeks of treatment
Secondary	Change in high-sensitivity C-reactive protein (hsCRP, mg/l )	Delta_ circulating hsCRP	from baseline to 12 weeks of treatment
Secondary	Change in N-terminal pro-brain natriuretic peptide (NTproBNP, ng,ml)	Delta_circulating NTproBNP	from baseline to 12 weeks of treatment
Secondary	Change in E/e' (average)	Delta_ E/e' (average) by 2D- echocardiography	from baseline to 12 weeks of treatment
Secondary	Change in Left ventricular global longitudinal strain (LVGLS,%)	Delta_ left ventricular global longitudinal strain by 2D speckle tracking-echocardiography	from baseline to 12 weeks of treatment
Secondary	Left atrial reservoir strain (LA reservoir strain ,%)	Delta_ LA reservoir strain by 2D speckle tracking-echocardiography	from baseline to 12 weeks of treatment
Secondary	Drug discontinuation	Frequency of drug discontinuation	during 12 weeks of treatment
Secondary	Incidence of side effects	Side effects will be registered and include gastrointestinal symptoms, hepatotoxicity, muscle weakness or pain, myotoxicity, renal dysfunction	during 12 weeks of treatment
Secondary	Change in insulin-like growth factor-binding protein 7 (IGFBP-7, ng/ml)	Delta_circulating IGFBP-7	from baseline to 12 weeks of treatment
Secondary	Change in procollagen type I carboxy-terminal propeptide (PICP, ng/ml)	Delta_circulating PICP	from baseline to 12 weeks of treatment
Secondary	Change in C-terminal telopeptide of collagen type I (CITP,ng/ml)	Delta_circulating CITP	from baseline to 12 weeks of treatment