ColchicinePhase 2DRC-04NCT03376698
Dose-finding Study of Colchicine in Type 2 Diabetic Patients With Coronary Artery Disease
A Phase 2 study testing Colchicine 0.5 mg and Colchicine 0.25 mg in people with Colchicine and Diabetes Mellitus, Type 2, run by University of the Ryukyus at 5 sites in Japan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Colchicine, Diabetes Mellitus, Type 2, Coronary Artery Disease
- What is being tested?
- Colchicine 0.5 mg and Colchicine 0.25 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 5 sitesJapan
- Study dates
- 15 Jun 2017to 1 Apr 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
- 1:"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).
- 2:"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.
- 3: 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.
Who cannot join
- 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.
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- 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.
- Patients whom physician in charge considered inappropriate for the study.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Japan5 sites
Hiroshima University Hospital
Hiroshima
Kitasato University Hospital
Kanagawa
Urasoe Sogo Hospital
Okinawa
Dokkyo Medical University Nikko Medical Center
Tochigi
Showa University Hospital
Tokyo
About this study
Official title: 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
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.
Read the 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
- Being tested
- Colchicine 0.5 mg, Colchicine 0.25 mg, Placebo
- Medical subject headings
- Diabetes Mellitus, Type 2, Coronary Artery Disease, Inflammation, Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Colchicine 0.5 mgDrug
oral administration of Colchicine 0.5 mg once daily for 12 weeks
Colchicine 0.25 mgDrug
oral administration of Colchicine 0.25 mg once daily for 12 weeks
PlaceboDrug
oral administration of Placebo once daily for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Colchicine 0.5 mg | Active comparator | Not described Receives: Drug: Colchicine 0.5 mg |
| Colchicine 0.25 mg | Active comparator | Not described Receives: Drug: Colchicine 0.25 mg |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in serum high-sensitivity CRP (mg/dl)
Measured: 4 weeks
Secondary outcomes (5)
Change in serum high-sensitivity CRP (mg/dl)
Measured: 12 weeks
Change in Flow Mediated Dilatation (%)
Measured: 12 weeks
Change in adhesive ability of white blood cell (number/field of view)
Measured: 4 weeks
Change in time through the microchannel of white blood cell (sec)
Measured: 4 weeks
Change in plasma myeloperoxidase level (ng/ml)
Measured: 4 and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2017
- Study start15 Jun 2017
- Primary completion4 Mar 2022
- Study completion1 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ColchicineStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of the Ryukyus
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shinichiro Ueda, University of the Ryukyus
- Investigators
- Shinichiro Ueda, PhD, Principal investigator, blessyou@med.u-ryukyu.ac.jp
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03376698
- Sponsor's protocol ID
- 1195
- Acronym
- DRC-04
- Status last verified
- May 2022
- First submitted
- 23 Oct 2017
- Last updated
- 12 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03376698
- Acronym / sponsor ID
- DRC-04 / 1195
- Conditions
- Colchicine, Diabetes Mellitus, Type 2, Coronary Artery Disease, White Blood Cell, Inflammation, Diarrhea
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- University of the RyukyusUniversity, hospital or other
- Study start
- 15 Jun 2017 (actual)
- Primary completion
- 4 Mar 2022 (actual)
- Study completion
- 1 Apr 2022 (actual)
- First posted
- 18 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- The subjects in this trial must have all of the following criteria.
Key exclusion criteria (16 listed)
- The subjects who conflict with at least one of the following criteria are exclude from this trial.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Colchicine 0.5 mgoral administration of Colchicine 0.5 mg once daily for 12 weeks | Drug | Colchicine 0.5 mg |
| Colchicine 0.25 mgoral administration of Colchicine 0.25 mg once daily for 12 weeks | Drug | Colchicine 0.25 mg |
| Placebooral administration of Placebo once daily for 12 weeks | Drug | Placebo |
Primary outcome
Change in serum high-sensitivity CRP (mg/dl)
Time frame: 4 weeks
5 secondary outcomes
Change in serum high-sensitivity CRP (mg/dl)
Time frame: 12 weeks
Change in Flow Mediated Dilatation (%)
Time frame: 12 weeks
Change in adhesive ability of white blood cell (number/field of view)
Time frame: 4 weeks
Change in time through the microchannel of white blood cell (sec)
Time frame: 4 weeks
Change in plasma myeloperoxidase level (ng/ml)
Time frame: 4 and 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2022.
- Individual participant dataSharing planned: Undecided
Related trials for Colchicine
Not yet recruiting
Hs-CRP-Guided Colchicine Treatment Targets in Very-High-Risk Patients With Coronary Artery Disease After PCI (TARGET-CHD)
Coronary Artery Disease, Atherosclerotic Cardiovascular Disease (ASCVD)
Not yet recruitingPhase 2
REducing Systemic Inflammation With LOw-dose Colchicine to ImproVE Cardiovascular Calcification in Chronic Kidney Disease: A Pilot Randomized Open-Label Trial
Chronic Kidney Disease Mineral and Bone Disorder, Cognitive Function
Not yet recruitingPhase 2
Colchicine in Pulmonary Artery Hypertension Patients
Pulmonary Hypertension
Not yet recruitingPhase 4
Anti-inflammatory and Anti-thrombotic Therapy With colcHicine and Low Dose Rivaroxaban for Major Adverse Cardiovascular Events Reduction in Ischemic Stroke
Ischemic Stroke
Active, not recruitingPhase 4
Pilot Trial of Colchicine for Graft Failure in CABG
CABG, Graft Failure
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shinichiro Ueda, PhD principal investigator
blessyou@med.u-ryukyu.ac.jp
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Colchicine 0.5 mg and Colchicine 0.25 mg in people with Colchicine and Diabetes Mellitus, Type 2, run by University of the Ryukyus at 5 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in serum high-sensitivity CRP (mg/dl) (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2022.