Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05949281
Other study ID # 2022-502038-23-00
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date August 29, 2023
Est. completion date June 15, 2026

Study information

Verified date November 2023
Source University Hospital, Gentofte, Copenhagen
Contact David S. Mathiesen, MD
Phone +4522996739
Email david.siersbaek.mathiesen.02@regionh.dk
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The aim of this clinical trial is to evaluate if colchicine in addition to standard of care improves markers of inflammation and cardiovascular disease in persons with type 1 diabetes. Participants will be assigned to either 0,5 mg colchicine daily or placebo in a 1:1 ratio for 26 weeks.


Description:

The current study aims to evaluate the efficacy of 0.5 mg colchicine once-daily added to existing standard of care in persons with established type 1 diabetes, existing arteriosclerotic cardiovascular disease (CVD) or at high risk thereof and C-reactive protein (CRP) ≥ 2 mg/L. Specifically, the primary objective is to determine the effect of colchicine (0.5 mg/daily) on levels of CRP (as assessed by high-sensitivity assays) as compared with placebo following 26 weeks of treatment. Additionally, the study will investigate the short and long-term effects of colchicine treatment on other markers of CVD and inflammation, markers of metabolism and markers of glycemic control in type 1 diabetes, including glycated hemoglobin (HbA1c), time spent in hypoglycemia (level 1 glucose readings 3.0-3.8 mmol/L and level 2 glucose readings < 3.0 mmol/L), target glycemia (glucose readings 3.9-10 mmol/L) and hyperglycemia (level 1 glucose readings 10.1-13.9 mmol/L and level 2 glucose readings > 13.9 mmol/L) together with measures of glycemic variability evaluated by continuous glucose monitoring (CGM), insulin dosage, risk of hypoglycemia, risk of diabetic ketoacidosis and body weight.


Recruitment information / eligibility

Status Recruiting
Enrollment 100
Est. completion date June 15, 2026
Est. primary completion date June 15, 2026
Accepts healthy volunteers No
Gender All
Age group 35 Years to 80 Years
Eligibility Inclusion Criteria: - Type 1 diabetes for more than five years according to World Health Organization criteria - Age 35-80 years - Hemoglobin A1c < 80 mmol/mol - Stable insulin therapy (defined as no change in insulin brand and no newly initiated continous subcutaneus insulin infusion (CSII) or multiple-daily injection (MDI) therapy) and, if applicable, stable usage of glucose monitoring technology (e.g., continous glucose monitor (CGM) or intermittently scanned CGM) = 3 months with either MDI or CSII - CRP = 2 mg/L (measured by high-sensitivity assay) - eGFR > 50 mL/min/L/1.73 m^2 - Either stable arteriosclerotic cardiovascular disease (ASCVD) (as defined by ischemic heart disease including previous acute myocardial infarction, acute coronary syndrome and coronary revascularization; other arterial revascularization procedures; stroke and transient ischemic attack; aortic aneurysm; peripheral arterial disease, including carotid atherosclerosis) - and/or risk of cardiovascular (CV) death > 5 % within 10 years (i.e., high or very high CV risk) as defined by the European Society of Cardiology or 10-year CV risk = 20 % (i.e., high CV risk) as according to 'Steno Type 1 Diabetes Risk Engine' (https://steno.shinyapps.io/T1RiskEngine/) Exclusion Criteria: - Hypoglycemia unawareness (inability to register low blood glucose) am modum Pedersen-Bjergaard, unless usage of CGM with alarm function - Liver disease with elevated plasma alanine aminotransferase (ALT) > three times the upper limit of normal (measured at screening with the possibility of one repeat analysis within seven days, and the last measured value as being conclusive) - History of cirrhosis, chronic active hepatitis or severe hepatic disease - Inflammatory bowel disease or chronic diarrhea - Pre-existing progressive neuromuscular disease or persons with creatinine kinase levels > three times the upper limit of normal (measured at screening with the possibility of one repeat analysis within a week, and the last measured value as being conclusive) - Cancer or lymphoproliferative disease unless in complete remission for > 5 years - Immunosuppressive therapy or state of chronic immunodeficiency, including infection with human immunodeficiency virus (HIV) - Blood dyscrasias (e.g., myelodysplastic syndromes or related hematological disorders) - Leukocyte cell count < 3.0 X 10^9/L - Thrombocyte count < 110 X 10^9/L - Systemic (oral or intravenous), long-term steroid therapy (topical or inhaled steroids are allowed) - Hemodialysis or peritoneal dialysis therapy (since colchicine cannot be removed by dialysis or exchange transfusion) - Renal or hepatic impairment treated with a P-gp inhibitor or a strong CYP3A4 inhibitor - Intake of grapefruit juice during trial participation - Other concomitant disease or treatment that according to the investigator's assessment makes the person unsuitable for study participation - Alcohol/drug abuse - Fertile women not using hormonal (tablet/pill, depot injection of progesterone, subdermal gestagen implantation, hormone intrauterine devices (IUD), hormonal vaginal ring or transdermal hormonal patch), chemical (copper IUD) or mechanical (condom, femidom, sterilization) contraceptives - Pregnant or nursing women - On permanent treatment with colchicine that is not discontinued within 30 days of screening visit - Known or suspected hypersensitivity to colchicine - Receipt of any investigational drug within 30 days prior to screening visit - Simultaneous participation in any other clinical intervention trial

Study Design


Intervention

Drug:
Colchicine 0.5 MG Oral Tablet
Colchicine 0.5 mg once-daily
Placebo
Placebo tablet once-daily

Locations

Country Name City State
Denmark Center for Clinical Metabolic Research, Gentofte Hospital Hellerup Capital Region

Sponsors (3)

Lead Sponsor Collaborator
Filip Krag Knop Juvenile Diabetes Research Foundation, University of Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type Measure Description Time frame Safety issue
Other Change in fasting serum/plasma concentrations of fibrinogen (µmol/L) %-point From week 0 (baseline) to week 30 (safety follow-up)
Other Change in fasting serum/plasma concentrations of serum amyloid A (mg/L) %-point From week 0 (baseline) to week 30 (safety follow-up)
Other Change in fasting serum/plasma concentrations of haptoglobin (g/L) %-point From week 0 (baseline) to week 30 (safety follow-up)
Other Change in fasting serum/plasma concentrations of interleukin (IL)-1ß (pg/mL) %-point From week 0 (baseline) to week 30 (safety follow-up)
Other Change in fasting serum/plasma concentrations of interleukin (IL)-2 (pg/mL) %-point From week 0 (baseline) to week 30 (safety follow-up)
Other Change in fasting serum/plasma concentrations of intercellular adhesion molecule 1 (ICAM-1) (pg/mL) %-point From week 0 (baseline) to week 30 (safety follow-up)
Other Change in fasting serum/plasma concentrations of vascular cell adhesion molecule 1 (VCAM-1) (pg/mL) %-point From week 0 (baseline) to week 30 (safety follow-up)
Other Change in fasting serum/plasma concentrations of total leukocyte count, including neutrophil, lymphocyte, basophil and eosinophil counts (10^9/L) %-point From week 0 (baseline) to week 30 (safety follow-up)
Other Change in neutrophil:lymphocyte ratio %-point From week 0 (baseline) to week 30 (safety follow-up)
Other Change in fasting serum/plasma concentrations of very low-density lipoprotein (VLDL) cholesterol (mmol/L) %-point From week 0 (baseline) to week 30 (safety follow-up)
Other Change in fasting serum/plasma concentrations of high-density lipoprotein (HDL) cholesterol (mmol/L) %-point From week 0 (baseline) to week 30 (safety follow-up)
Other Change in fasting serum/plasma concentrations of total cholesterol (mmol/L) %-point From week 0 (baseline) to week 30 (safety follow-up)
Other Change in fasting serum/plasma concentrations of triglycerides (mmol/L) %-point From week 0 (baseline) to week 30 (safety follow-up)
Other Change in fasting serum/plasma concentrations of lipoprotein (a) (mg/L) %-point From week 0 (baseline) to week 30 (safety follow-up)
Other Change in thrombocyte function measured by thromboelastography %-point From week 0 (baseline) to week 26 (end of treatment)
Other Change in fasting serum/plasma concentrations of N-terminal pro-brain natriuretic peptide (pro-BNP) (pmol/L) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in consultation blood pressure (mmHg) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in heart rate (beats/minute) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in fasting serum/plasma concentrations of estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in fasting serum/plasma concentrations of albumin (g/L) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in urine albumin-to-creatinine ratio (mg/g) %-point From week 0 (baseline) to week 26 (end of treatment)
Other Change left ventricular (LV) mass index evaluated by cardiovascular ultrasonography (g/m^2) %-point From week 0 (baseline) to week 26 (end of treatment)
Other Change left ventricular (LV) septal wall thickness evaluated by cardiovascular ultrasonography (mm) %-point From week 0 (baseline) to week 26 (end of treatment)
Other Change left ventricular (LV) posterior wall thickness evaluated by cardiovascular ultrasonography (mm) %-point From week 0 (baseline) to week 26 (end of treatment)
Other Change left ventricular (LV) ejection fraction (LVEF) evaluated by cardiovascular ultrasonography (%) %-point From week 0 (baseline) to week 26 (end of treatment)
Other Change ratio of peak velocity blood flow from left ventricular relaxation in early diastole (E) to peak velocity flow in late diastole caused by atrial contraction (A) (E/A ratio) evaluated by cardiovascular ultrasonography %-point From week 0 (baseline) to week 26 (end of treatment)
Other Change early diastolic mitral inflow velocity (e') evaluated by cardiovascular ultrasonography (m/sec) %-point From week 0 (baseline) to week 26 (end of treatment)
Other Change ratio of early diastolic mitral inflow velocity (e') to early diastolic mitral annulus velocity (E) (E/e' ratio) evaluated by cardiovascular ultrasonography %-point From week 0 (baseline) to week 26 (end of treatment)
Other Change ratio of early mitral inflow velocity (E) to global diastolic strain rate (e' sr) (E/e'sr ratio) evaluated by cardiovascular ultrasonography %-point From week 0 (baseline) to week 26 (end of treatment)
Other Change left atrial volume (LAVi) evaluated by cardiovascular ultrasonography (mL) %-point From week 0 (baseline) to week 26 (end of treatment)
Other Change global longitudinal strain (GLS) evaluated by cardiovascular ultrasonography (%) %-point From week 0 (baseline) to week 26 (end of treatment)
Other Change aortic distensibility evaluated by cardiovascular ultrasonography (mmHg^-1) %-point From week 0 (baseline) to week 26 (end of treatment)
Other Change aortic strain evaluated by cardiovascular ultrasonography (%) %-point From week 0 (baseline) to week 26 (end of treatment)
Other Change in mean glucose evaluated by a continous glucose monitor (mmol/L) %-point From week 0 (baseline) to week 26 (end of treatment)
Other Change in standard deviation evaluated by a continous glucose monitor (mmol/L) %-point From week 0 (baseline) to week 26 (end of treatment)
Other Change in coefficient of variance evaluated by a continous glucose monitor (> 0.36 defined as glycemic variability) %-point From week 0 (baseline) to week 26 (end of treatment)
Other Change in glycemic variability (continuous overall net glycemic action (CONGA)) evaluated by a continous glucose monitor %-point From week 0 (baseline) to week 26 (end of treatment)
Other Change in mean amplitude of glycemic excursion evaluated by a continous glucose monitor %-point From week 0 (baseline) to week 26 (end of treatment)
Other Change in diabetes treatment satisfactory questionnaire, status version (DTSQs) (From 0 (min) to 6 (max), higher scores indicate a better outcome ) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in diabetes treatment satisfactory questionnaire, change version (DTSQc) (From -3 (min) to 3 (max), higher scores indicate a better outcome) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in audit of diabetes-dependent quality of life questionnaire (ADDQoL) (From -9 (min) to 9 (max), higher scores indicate a better outcome ) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in fasting serum/plasma concentrations of ketones (mmol/L) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Adverse events As reported by participants From week 0 (baseline) to week 30 (end of treatment)
Other Change in liver fat content as per the CAP score (dB/m) measured by FibroScan® %-point From week 0 (baseline) to week 26 (end of treatment)
Other Change in liver fibrosis score (kPa) measured by FibroScan® %-point From week 0 (baseline) to week 26 (end of treatment)
Other Change in fibrosis-4 (FIB-4) score (numerical scale, higher scores indicate a higher risk of fibrosis) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in fatty liver index (FLI) score (numerical scale, higher scores indicate a higher risk of fibrosis) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in fasting serum/plasma concentrations of hemoglobin (mmol/L) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in fasting serum/plasma concentrations of thrombocytes (10^9/L) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in fasting serum/plasma concentrations of glucose (mmol/L) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in fasting serum/plasma concentrations of potassium (mmol/L) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in fasting serum/plasma concentrations of sodium (mmol/L) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in fasting serum/plasma concentrations of creatinine (umol/L) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in fasting serum/plasma concentrations of alanine aminotransferase (U/L) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in fasting serum/plasma concentrations of aspartate aminotransferase (U/L) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in fasting serum/plasma concentrations of bilirubin (umol/L) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in fasting serum/plasma concentrations of amylase (units/L) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in fasting serum/plasma concentrations of creatine kinase (U/L) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in fasting serum/plasma concentrations of C-peptide (pmol/L) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in fasting serum/plasma concentrations of glucagon (pmol/L) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in fasting serum/plasma concentrations of C-terminal telopeptide (ng/L) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in fasting serum/plasma concentrations of procollagen type 1 N-terminal propeptide (ng/L) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in body composition by bioimpedance analysis %-point (fat free mass, total fat mass, muscle mass, bone mass) From week 0 (baseline) to week 26 (end of treatment)
Other Change in body mass index (kg/m^2) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in waist circumference (cm) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in hip circumference (cm) %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in waist:hip ratio %-point From week 0 (baseline) to week 30 (end of treatment)
Other Change in interleukin messenger ribonucleic acid (mRNA) expression measured by quantitative polymerase chain reaction %-point From week 0 (baseline) to week 26 (end of treatment)
Primary Change in fasting serum/plasma concentrations of C-reactive protein (CRP) measured by a high-sensitivity assay (hsCRP) (mg/L) %-point From week 0 (baseline) to week 26 (end of treatment)
Secondary Change in fasting serum/plasma concentrations of C-reactive protein (CRP) measured by a high-sensitivity assay (hsCRP) (mg/L) %-point From week 0 (baseline) to week 30 (safety follow-up)
Secondary Change in fasting serum/plasma concentrations of hemoglobin A1c (mmol/mol) %-point From week 0 (baseline) to week 30 (safety follow-up)
Secondary Time spent in target blood glucose range (3.9 - 10 mmol/L) evaluated by a continous glucose monitor (CGM) (% of 24 hours) From week 0 (baseline) to week 26 (end of treatment)
Secondary Time spent in hyperglycemia level 1 (10-13.9 mmol/L) evaluated by a continous glucose monitor (CGM) (% of 24 hours) From week 0 (baseline) to week 26 (end of treatment)
Secondary Time spent in hyperglycemia level 2 (> 13.9 mmol/L) evaluated by a continous glucose monitor (CGM) (% of 24 hours) From week 0 (baseline) to week 26 (end of treatment)
Secondary Time spent in hypoglycemia level 1 (3.0-3.8 mmol/L) evaluated by a continous glucose monitor (CGM) (% of 24 hours) From week 0 (baseline) to week 26 (end of treatment)
Secondary Time spent in hypoglycemia level 2 (< 3.0 mmol/L)evaluated by a continous glucose monitor (CGM) (% of 24 hours) From week 0 (baseline) to week 26 (end of treatment)
Secondary Insulin dosage Number of units/day (both long- and short-acting insulin analogues) From week 0 (baseline) to week 30 (safety follow-up)
Secondary Change in body weight (kg) %-point From week 0 (baseline) to week 30 (safety follow-up)
Secondary Change in waist:hip ratio %-point From week 0 (baseline) to week 30 (safety follow-up)
Secondary Change in fasting serum/plasma concentrations of low-density lipoprotein cholesterol (LDL) (mmol/L) %-point From week 0 (baseline) to week 30 (safety follow-up)
Secondary Change in fasting serum/plasma concentrations of interleukin (IL)-6 (pg/mL) %-point From week 0 (baseline) to week 30 (safety follow-up)
Secondary Change in fasting serum/plasma concentrations of tumor necrosis factor alpha (pg/mL) %-point From week 0 (baseline) to week 30 (safety follow-up)
Secondary Safety-related events Serious adverse events (SAE), events of severe hypoglycemia, events of diabetic ketoacidosis From week 0 (baseline) to week 30 (safety follow-up)
See also
  Status Clinical Trial Phase
Recruiting NCT05650307 - CV Imaging of Metabolic Interventions
Recruiting NCT05654272 - Development of CIRC Technologies
Recruiting NCT04515303 - Digital Intervention Participation in DASH
Completed NCT04056208 - Pistachios Blood Sugar Control, Heart and Gut Health Phase 2
Recruiting NCT04417387 - The Genetics and Vascular Health Check Study (GENVASC) Aims to Help Determine Whether Gathering Genetic Information Can Improve the Prediction of Risk of Coronary Artery Disease (CAD)
Not yet recruiting NCT06211361 - Cardiac Rehabilitation Program in Patients With Cardiovascular Disease N/A
Not yet recruiting NCT06032572 - Evaluation of the Safety and Effectiveness of the VRS100 System in PCI (ESSENCE) N/A
Recruiting NCT04514445 - The BRAVE Study- The Identification of Genetic Variants Associated With Bicuspid Aortic Valve Using a Combination of Case-control and Family-based Approaches.
Enrolling by invitation NCT04253054 - Chinese Multi-provincial Cohort Study-Beijing Project
Completed NCT03273972 - INvestigating the Lowest Threshold of Vascular bENefits From LDL Lowering With a PCSK9 InhibiTor in healthY Volunteers N/A
Completed NCT03680638 - The Effect of Antioxidants on Skin Blood Flow During Local Heating Phase 1
Recruiting NCT04843891 - Evaluation of PET Probe [64]Cu-Macrin in Cardiovascular Disease, Cancer and Sarcoidosis. Phase 1
Completed NCT04083872 - Clinical Study to Investigate the Pharmacokinetic Profiles and Safety of Highdose CKD-385 in Healthy Volunteers(Fasting) Phase 1
Completed NCT04083846 - Clinical Study to Investigate the Pharmacokinetic Profiles and Safety of High-dose CKD-385 in Healthy Volunteers(Fed) Phase 1
Completed NCT03619148 - The Incidence of Respiratory Symptoms Associated With the Use of HFNO N/A
Completed NCT03466333 - Postnatal Enalapril to Improve Cardiovascular fUnction Following Preterm Pre-eclampsia Phase 2
Completed NCT03693365 - Fluid Responsiveness Tested by the Effective Pulmonary Blood Flow During a Positive End-expiratory Trial
Completed NCT04082585 - Total Health Improvement Program Research Project
Completed NCT05132998 - Impact of a Comprehensive Cardiac Rehabilitation Program Framework Among High Cardiovascular Risk Cancer Survivors N/A
Completed NCT05067114 - Solutions for Atrial Fibrillation Edvocacy (SAFE)