NCT03376698

Dose-finding Study of Colchicine in Type 2 Diabetic Patients With Coronary Artery Disease

A Randomized, Double-blind, Placebo-controlled Phase II Trial to Evaluate the Dose-dependent Effect of Colchicine on Inflammatory Response and Endothelial Function in Type 2 Diabetic Patients With Coronary Artery Disease and Leukocyte Activation

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 54 (actual)
• Sponsor: University of the Ryukyus · Academic / Other
• Sex: All
• Age: 20 Years
• Healthy volunteers: Not accepted

Summary

This study is designed to investigate dose-dependent effects of low dose colchicine on inflammatory responses, endothelial function in type 2 diabetic patients with coronary artery disease and leukocyte activation. This study also tested the relationship between doses and safety issue such as incidence of diarrhea. Eligible patients will be randomly allocated to three treatment group: colchicine at 0.5mg per day, 0.25mg per day or placebo for 12 weeks in a double blind , parallel group design. High sensitive-CRP at 4 weeks as primary end point and flow mediated vasodilatation at 12 weeks as the secondary end point will be measured.

Detailed description

Mortality rate in Japanese coronary artery disease (CAD) patients has been deemed the lowest among developed countries for the long time. However, cohort study of the investigators based on the registry of 8000 patients with CAD and type 2 diabetes has shown that cardiovascular mortality of such patients even under the optimized standard therapy and relatively intensive control of risk factors was higher than the investigators thought. Given substantial experimental evidence suggesting roles of inflammation as a key player in the development of atherosclerosis and significant association of enhanced inflammatory reaction and cardiovascular events in registry-based cohort of the investigators, the investigators are planning of phase 3 trial of colchicine, which is an ancient anti-inflammatory drug, for the regulatory approval as a drug preventing of cardiovascular events in diabetic CAD patients with enhanced inflammatory reaction. To develop appropriate study protocol of phase 3 trial, a dose-finding study is apparently warranted since our pharmacokinetics study and pharmacokinetics /pharmacodynamics study showed that colchicine stays in leukocytes with a long half life being more than 40 hours and showed consistent inhibition of leukocyte activation for more than 48 hours. In terms of safety issue, 0.5mg of colchicine, which has been frequently used in several cardiovascular trials, is associated with high incidence of diarrhea. As dose-dependency is assumed regarding diarrhea, a dose finding study for safety issue is also needed. The investigators, thus, conduct a double-blind randomized controlled trial to investigate dose-dependent effects on inflammatory responses using highly sensitive-CRP as an indicator, endothelial function using FMD, and incidence of diarrhea comparing once daily oral administration of 0.5 mg, 0.25 mg of colchicine and placebo for 12 weeks in CAD patients with type 2 diabetes mellitus and leukocyte activation. The investigators focus on patients with type 2 diabetes and leukocyte activation among CAD patients for regulatory approval because it is likely that such patients are at highest risk and respond well to colchicine.

Conditions

• Colchicine
• Diabetes Mellitus, Type 2
• Coronary Artery Disease
• White Blood Cell
• Inflammation
• Diarrhea

Interventions

Type	Name	Description
DRUG	Colchicine 0.5 mg	oral administration of Colchicine 0.5 mg once daily for 12 weeks
DRUG	Colchicine 0.25 mg	oral administration of Colchicine 0.25 mg once daily for 12 weeks
DRUG	Placebo	oral administration of Placebo once daily for 12 weeks

Timeline

• Start date: 2017-06-15
• Primary completion: 2022-03-04
• Completion: 2022-04-01
• First posted: 2017-12-18
• Last updated: 2022-05-12

Locations

5 sites across 1 country: Japan