Repurposing Colchicine for Reduction of Residual Inflammatory Risk in Type 1 Diabetes

NCT05949281 | Active Not Recruiting Phase 2

• 1 other identifier: 2022-502038-23-00
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Type 1 Diabetes; Cardiovascular Diseases; Chronic Inflammation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• Change in fasting serum/plasma concentrations of C-reactive protein (CRP) measured by a high-sensitivity assay (hsCRP) (mg/L)

  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)

  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)

  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)

  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)

  From week 0 (baseline) to week 26 (end of treatment) or to 52 weeks (extension)

Other Outcomes (68)

• Change in fasting serum/plasma concentrations of fibrinogen (µmol/L)

  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)

  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)

  From week 0 (baseline) to week 30 (safety follow-up) or to 56 weeks (extension)

Study Arms (2)

Colchicine

ACTIVE COMPARATOR

Colchicine tablet 0.5 mg once-daily

Drug: Colchicine 0.5 MG Oral Tablet

Placebo

PLACEBO COMPARATOR

Placebo tablet once-daily

Drug: Placebo

Interventions

Colchicine 0.5 MG Oral Tablet DRUG

Colchicine 0.5 mg once-daily

Also known as: Colrefuz

Colchicine

Placebo DRUG

Placebo tablet once-daily

Placebo

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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/)

You may not qualify if:

• 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

Sponsors & Collaborators

• Asger Lund, MD: lead
• University of Copenhagen: collaborator
• Juvenile Diabetes Research Foundation: collaborator

Study Sites (1)

Center for Clinical Metabolic Research, Gentofte Hospital

Hellerup, Capital Region, 2900, Denmark

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Cardiovascular Diseases

Interventions

Colchicine; Tablets

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Asger B. Lund, MD, PhD

  Center for Clinical Metabolic Research, Gentofte Hospital, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Ass. Professor, MD, PhD

Study Record Dates

• First Submitted: June 29, 2023
• First Posted: July 18, 2023
• Study Start: August 29, 2023
• Primary Completion (Estimated): January 15, 2031
• Study Completion (Estimated): January 15, 2031
• Last Updated: January 26, 2026

Record last verified: 2026-01

Locations

DK (1)