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| Name | Class |
|---|---|
| University of Copenhagen | OTHER |
| Juvenile Diabetes Research Foundation | OTHER |
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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 with the possibility of an additional 26 week extension of the intervention period. After the treatment period, there will a 5-year follow-up on all available outcome measures via electronic patient records for those who took part in the extension.
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 26-52 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. During the 5-year follow-up, we will collect all available outcome measures via electronic patient records.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Colchicine | Active Comparator | Colchicine tablet 0.5 mg once-daily |
|
| Placebo | Placebo Comparator | Placebo tablet once-daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Colchicine 0.5 MG Oral Tablet | Drug | Colchicine 0.5 mg once-daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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) or to 56 weeks (extension) |
| Change in fasting serum/plasma concentrations of hemoglobin A1c (mmol/mol) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in fasting serum/plasma concentrations of fibrinogen (µmol/L) | %-point | From week 0 (baseline) to week 30 (safety follow-up) or to 56 weeks (extension) |
| Change in fasting serum/plasma concentrations of serum amyloid A (mg/L) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Asger B. Lund, MD, PhD | Center for Clinical Metabolic Research, Gentofte Hospital, Denmark | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Center for Clinical Metabolic Research, Gentofte Hospital | Hellerup | Capital Region | 2900 | Denmark |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D002318 | Cardiovascular Diseases |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D003078 | Colchicine |
| D013607 | Tablets |
| ID | Term |
|---|---|
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
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| Placebo | Drug | Placebo tablet once-daily |
|
%-point |
| From week 0 (baseline) to week 30 (safety follow-up) or to 56 weeks (extension) |
| 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) or to 52 weeks (extension) |
| 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) or to 52 weeks (extension) |
| 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) or to 52 weeks (extension) |
| 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) or to 52 weeks (extension) |
| 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) or to 52 weeks (extension) |
| Insulin dosage | Number of units/day (both long- and short-acting insulin analogues) | From week 0 (baseline) to week 30 (safety follow-up) or to 56 weeks (extension) |
| Change in body weight (kg) | %-point | From week 0 (baseline) to week 30 (safety follow-up) or to 56 weeks (extension) |
| Change in waist:hip ratio | %-point | From week 0 (baseline) to week 30 (safety follow-up) or to 56 weeks (extension) |
| 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) or to 56 weeks (extension) |
| Change in fasting serum/plasma concentrations of interleukin (IL)-6 (pg/mL) | %-point | From week 0 (baseline) to week 30 (safety follow-up) or to 56 weeks (extension) |
| Change in fasting serum/plasma concentrations of tumor necrosis factor alpha (pg/mL) | %-point | From week 0 (baseline) to week 30 (safety follow-up) or to 56 weeks (extension) |
| 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) or to 56 weeks (extension) |
%-point
| From week 0 (baseline) to week 30 (safety follow-up) or to 56 weeks (extension) |
| Change in fasting serum/plasma concentrations of haptoglobin (g/L) | %-point | From week 0 (baseline) to week 30 (safety follow-up) or to 56 weeks (extension) |
| Change in fasting serum/plasma concentrations of interleukin (IL)-1β (pg/mL) | %-point | From week 0 (baseline) to week 30 (safety follow-up) or to 56 weeks (extension) |
| Change in fasting serum/plasma concentrations of interleukin (IL)-2 (pg/mL) | %-point | From week 0 (baseline) to week 30 (safety follow-up) or to 56 weeks (extension) |
| 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) or to 56 weeks (extension) |
| 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) or to 56 weeks (extension) |
| 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) or to 56 weeks (extension) |
| Change in neutrophil:lymphocyte ratio | %-point | From week 0 (baseline) to week 30 (safety follow-up) or to 56 weeks (extension) |
| 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) or to 56 weeks (extension) |
| 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) or to 56 weeks (extension) |
| Change in fasting serum/plasma concentrations of total cholesterol (mmol/L) | %-point | From week 0 (baseline) to week 30 (safety follow-up) or to 56 weeks (extension) |
| Change in fasting serum/plasma concentrations of triglycerides (mmol/L) | %-point | From week 0 (baseline) to week 30 (safety follow-up) or to week 56 (extension) |
| Change in fasting serum/plasma concentrations of lipoprotein (a) (mg/L) | %-point | From week 0 (baseline) to week 30 (safety follow-up) or to week 56 (extension) |
| Change in thrombocyte function measured by thromboelastography | %-point | From week 0 (baseline) to week 26 (end of treatment) or to week 52 (extension) |
| 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) or to week 56 (extension) |
| Change in consultation blood pressure (mmHg) | %-point | From week 0 (baseline) to week 30 (end of treatment) or to week 56 (extension) |
| Change in heart rate (beats/minute) | %-point | From week 0 (baseline) to week 30 (end of treatment) or to week 56 (extension) |
| 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) or to week 56 (extension) |
| Change in fasting serum/plasma concentrations of albumin (g/L) | %-point | From week 0 (baseline) to week 30 (end of treatment) or to week 56 (extension) |
| Change in urine albumin-to-creatinine ratio (mg/g) | %-point | From week 0 (baseline) to week 26 (end of treatment) or to week 56 (extension) |
| Change left ventricular (LV) mass index evaluated by cardiovascular ultrasonography (g/m^2) | %-point | From week 0 (baseline) to week 26 (end of treatment) |
| Change left ventricular (LV) septal wall thickness evaluated by cardiovascular ultrasonography (mm) | %-point | From week 0 (baseline) to week 26 (end of treatment) |
| Change left ventricular (LV) posterior wall thickness evaluated by cardiovascular ultrasonography (mm) | %-point | From week 0 (baseline) to week 26 (end of treatment) |
| Change left ventricular (LV) ejection fraction (LVEF) evaluated by cardiovascular ultrasonography (%) | %-point | From week 0 (baseline) to week 26 (end of treatment) |
| 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) |
| Change early diastolic mitral inflow velocity (e') evaluated by cardiovascular ultrasonography (m/sec) | %-point | From week 0 (baseline) to week 26 (end of treatment) |
| 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) |
| 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) |
| Change left atrial volume (LAVi) evaluated by cardiovascular ultrasonography (mL) | %-point | From week 0 (baseline) to week 26 (end of treatment) |
| Change global longitudinal strain (GLS) evaluated by cardiovascular ultrasonography (%) | %-point | From week 0 (baseline) to week 26 (end of treatment) |
| Change aortic distensibility evaluated by cardiovascular ultrasonography (mmHg^-1) | %-point | From week 0 (baseline) to week 26 (end of treatment) |
| Change aortic strain evaluated by cardiovascular ultrasonography (%) | %-point | From week 0 (baseline) to week 26 (end of treatment) |
| Change in mean glucose evaluated by a continous glucose monitor (mmol/L) | %-point | From week 0 (baseline) to week 26 (end of treatment) or to week 52 (extension) |
| Change in standard deviation evaluated by a continous glucose monitor (mmol/L) | %-point | From week 0 (baseline) to week 26 (end of treatment) or to week 52 (extension) |
| 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) or to week 52 (extension) |
| 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) or to week 52 (extension) |
| Change in mean amplitude of glycemic excursion evaluated by a continous glucose monitor | %-point | From week 0 (baseline) to week 26 (end of treatment) or to week 52 (extension) |
| 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) or to week 56 (extension) |
| 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) or to week 56 (extension) |
| 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) or to week 56 (extension) |
| Change in fasting serum/plasma concentrations of ketones (mmol/L) | %-point | From week 0 (baseline) to week 30 (end of treatment) or to week 56 (extension) |
| Adverse events | As reported by participants | From week 0 (baseline) to week 30 (end of treatment) or to week 56 (extension) |
| 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) or to week 52 (extension) |
| Change in liver fibrosis score (kPa) measured by FibroScan® | %-point | From week 0 (baseline) to week 26 (end of treatment) or to week 52 (extension) |
| 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) or to week 56 (extension) |
| 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) or to week 56 (extension) |
| Change in fasting serum/plasma concentrations of hemoglobin (mmol/L) | %-point | From week 0 (baseline) to week 30 (end of treatment) or to week 56 (extension) |
| Change in fasting serum/plasma concentrations of thrombocytes (10^9/L) | %-point | From week 0 (baseline) to week 30 (end of treatment) or to week 56 (extension) |
| Change in fasting serum/plasma concentrations of glucose (mmol/L) | %-point | From week 0 (baseline) to week 30 (end of treatment) or to week 56 (extension) |
| Change in fasting serum/plasma concentrations of potassium (mmol/L) | %-point | From week 0 (baseline) to week 30 (end of treatment) or to week 56 (extension) |
| Change in fasting serum/plasma concentrations of sodium (mmol/L) | %-point | From week 0 (baseline) to week 30 (end of treatment) or to week 56 (extension) |
| Change in fasting serum/plasma concentrations of creatinine (umol/L) | %-point | From week 0 (baseline) to week 30 (end of treatment) or to week 56 (extension) |
| Change in fasting serum/plasma concentrations of alanine aminotransferase (U/L) | %-point | From week 0 (baseline) to week 30 (end of treatment) or to week 56 (extension) |
| Change in fasting serum/plasma concentrations of aspartate aminotransferase (U/L) | %-point | From week 0 (baseline) to week 30 (end of treatment) or to week 56 (extension) |
| Change in fasting serum/plasma concentrations of bilirubin (umol/L) | %-point | From week 0 (baseline) to week 30 (end of treatment) or to week 56 (extension) |
| Change in fasting serum/plasma concentrations of amylase (units/L) | %-point | From week 0 (baseline) to week 30 (end of treatment) or to week 56 (extension) |
| Change in fasting serum/plasma concentrations of creatine kinase (U/L) | %-point | From week 0 (baseline) to week 30 (end of treatment) or to week 56 (extension) |
| Change in fasting serum/plasma concentrations of C-peptide (pmol/L) | %-point | From week 0 (baseline) to week 30 (end of treatment) or to week 56 (extension) |
| Change in fasting serum/plasma concentrations of glucagon (pmol/L) | %-point | From week 0 (baseline) to week 30 (end of treatment) or to week 56 (extension) |
| Change in fasting serum/plasma concentrations of C-terminal telopeptide (ng/L) | %-point | From week 0 (baseline) to week 30 (end of treatment) or to week 56 (extension) |
| 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) or to week 56 (extension) |
| 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) or to week 52 (extension) |
| Change in body mass index (kg/m^2) | %-point | From week 0 (baseline) to week 30 (end of treatment) or to week 56 (extension) |
| Change in waist circumference (cm) | %-point | From week 0 (baseline) to week 30 (end of treatment) or to week 56 (extension) |
| Change in hip circumference (cm) | %-point | From week 0 (baseline) to week 30 (end of treatment) or to week 56 (extension) |
| Change in waist:hip ratio | %-point | From week 0 (baseline) to week 30 (end of treatment) or to week 56 (extension) |
| 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) or to week 56 (extension) |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |