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

NCT03376698 | Completed Phase 2 DMC

• 1 other identifier: 1195
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Change in serum high-sensitivity CRP (mg/dl)

  4 weeks

Secondary Outcomes (5)

• Change in serum high-sensitivity CRP (mg/dl)

  12 weeks

• Change in Flow Mediated Dilatation (%)

  12 weeks

• Change in adhesive ability of white blood cell (number/field of view)

  4 weeks

• Change in time through the microchannel of white blood cell (sec)

  4 weeks

• Change in plasma myeloperoxidase level (ng/ml)

  4 and 12 weeks

Other Outcomes (6)

• Cardiovascular events

  12 weeks

• Adverse events

  12 weeks

• Side effect

  12 weeks

Study Arms (3)

Colchicine 0.5 mg

ACTIVE COMPARATOR

Drug: Colchicine 0.5 mg

Colchicine 0.25 mg

ACTIVE COMPARATOR

Drug: Colchicine 0.25 mg

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Colchicine 0.5 mg DRUG

oral administration of Colchicine 0.5 mg once daily for 12 weeks

Colchicine 0.5 mg

Colchicine 0.25 mg DRUG

oral administration of Colchicine 0.25 mg once daily for 12 weeks

Colchicine 0.25 mg

Placebo DRUG

oral administration of Placebo once daily for 12 weeks

Placebo

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subjects in this trial must have all of the following criteria.
• Patients with type 2 diabetes mellitus with coronary artery disease(\*1) with increased inflammatory response(\*2).
• :"Type 2 diabetes" mellitus is diagnosed by criteria according to The Japan Diabetes Society. "Coronary artery disease" is defined as having equal to or greater than 75% stenosis in coronary angiography, history of acute coronary syndrome, and history of coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI).
• :"Increased inflammatory response" is defined as follow; White blood cell levels at confirmation tests of eligibility is equal to or greater than 7000 /μL.
• Patients aged 20 years and older
• In female subjects who had possibility of pregnancy and male subjects who had female partner who had possibility of pregnancy and not undergone a contraceptive surgery(\*3), patients with consent of performing optimal contraception from starting study drug to 90 days from final taking.
• : Male subjects who had undergone a contraceptive surgery are defined as elapsing for at least one year after vasectomy and having a certification of no sperm at ejaculation.
• After receiving sufficient explanation for the participation of this study, patients who wrote document of informed consent by the patient's free will with sufficient understanding.

You may not qualify if:

• The subjects who conflict with at least one of the following criteria are exclude from this trial.
• Patients with prior hypersensitivity to Colchicine.
• Patients with taking Colhicine presently or to 30 days before confirmation tests of eligibility.
• Patients with liver cirrhosis
• Patients with clinical cholestasis.
• Patients with decreasing renal function (eGFR \< 30 mL/min/1.73m2) at confirmation tests of eligibility.
• Patients with active malignancy.
• Patients taking drugs that are indicated as "combined caution" in the package insert of Colchicine as a drug which may interact with Colchicine. 1. Drugs inhibiting cytochrome P450 drug-metabolizing enzyme
• Strong Inhibitor Atazanavir, Clarithromycin, Indinavir, Itraconazole, Nelfinavir, Ritonavir, Saquinavir, Darunavir, Telithromycin, Telaprevir, Preparation including Cobicistat
• Moderate Inhibitor Amprenavir, Aprepitant, Diltiazem, Erythromycin, Fluconazole, Fosamprenavir, Verapamil 2. P-glycoprotein inhibitor Ciclosporin
• Patients taking Amiodarone or Quinidine.
• Patients with infectious or inflammatory disease at confirmation tests of eligibility.
• Current smoker
• Patients with pregnancy, possible pregnancy, on breast-feeding or who wish to become pregnant during trial. (The female subjects who had possibility of pregnancy receive a pregnancy test.)
• Patients registered in other clinical trials presently or within 30 days before acquisition consent of this trial.

Sponsors & Collaborators

• University of the Ryukyus: lead

Study Sites (5)

Hiroshima University Hospital

Hiroshima, Japan

Location

Kitasato University Hospital

Kanagawa, Japan

Location

Urasoe Sogo Hospital

Okinawa, Japan

Location

Dokkyo Medical University Nikko Medical Center

Tochigi, Japan

Location

Showa University Hospital

Tokyo, Japan

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Coronary Artery Disease; Inflammation; Diarrhea

Interventions

Colchicine

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Digestive; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Study Officials

• Shinichiro Ueda, PhD

  blessyou@med.u-ryukyu.ac.jp

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 23, 2017
• First Posted: December 18, 2017
• Study Start: June 15, 2017
• Primary Completion: March 4, 2022
• Study Completion: April 1, 2022
• Last Updated: May 12, 2022

Record last verified: 2022-05

Locations

JP (5)