The Effect of Colchicine, on Insulin Sensitivity in Individuals With Type 1 Diabetes and Systemic Low-grade Inflammation (INS1GHT)

The Effect of Colchicine, on Insulin Sensitivity in Individuals With Type 1 Diabetes and Systemic Low-grade Inflammation: A Randomized, Double-Blind, Placebo-Controlled, Investigator-Initiated Trial

The aim for this clinical trial is to evaluate if colchicine in addition to standard of care improves insulin sensitivity in individuals with type 1 diabetes, systemic low-grade inflammaiton and reduced insulin sensitivity. The insulin sensitivity will be evaluated by a hyperinsulinemic, euglycemic clamp.

Study Overview

• Status: Recruiting
• Conditions: Type 1 Diabetes; Chronic Inflammation; Insulin Sensitivity
• Intervention / Treatment: Drug: Colchicin 0.5 mg once daily for two weeks, then twice daily for two weeks; Drug: Placebo once daily for two weeks, then twice daily for two weeks; Drug: Placebo once daily for two weeks, then twice daily for two weeks; Drug: Colchicine tablet 0.5 mg once-daily for two weeks, then twice daily for two weeks

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Askee N. Høck, MD; Phone Number: +4561275585; Email: aske.nicolai.hoeck@regionh.dk

Study Locations

• Denmark
  • Gentofte Municipality, Denmark, 2400
    • Recruiting
    • Center for Clinical Metabolic Research, Gentofte Hospital, Hellerup, Capital Region 2900
    • Contact: Asger B Lund, MD, PhD; Phone Number: 004538674266; Email: asger.lund.01@regionh.dk
    • Contact: Aske N Høck, MD; Phone Number: 004561275585; Email: aske.nicolai.hoeck@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Type 1 diabetes for more than five years according to World Health Organization criteria and c-peptid <200 pmol/L
• Age 18-80 years
• User of a continuous glucose monitor (CGM) system
• Glycated hemoglobin A1c (HbA1c) 42-75 mmol/mol
• Stable insulin therapy (defined as no change in insulin brand and no newly initiated Continuous subcutaneous insulin infusion (CSII) or Multiple dose injection (MDI) therapy) and, if applicable, stable usage of glucose monitoring technology (e.g., continuous glucose monitor or intermittently scanned continuous glucose monitor) ≥ 3 months with either multiple daily injections or continuous subcutaneous insulin infusion
• Estimated glomerular filtration rate ≥ 60 mL/min/L/1.73 m²
• Estimated glucose disposal rate (eGDR)* < 8 mg/kg/min OR insulin usage of ≥1 IU/kg pr day
• C-reactive protein (CRP) hsCRP ≥ 2 mg/L, (measured by high-sensitivity assay)**

Exclusion Criteria:

• Hypoglycaemia unawareness (inability to register low blood glucose) ad modum Pedersen-Bjergaard, 24 unless the individual uses a continuous glucose monitor with alarm function
• Liver disease with elevated plasma alanine aminotransferase (ALT) > three times the upper limit of normal (measured at screening visit 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 diarrhoea
• Pre-existing progressive neuromuscular disease or individuals with creatinine kinase levels > three times the upper limit of normal (measured at screening visit 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
• Blood dyscrasias (e.g., myelodysplastic syndromes or related haematological disorders)
• Leukocyte cell count < 3.0 X 109/L
• Thrombocyte count < 110 X 109/L
• Immunosuppressive therapy or state of chronic immunodeficiency, including infection with human immunodeficiency virus (HIV)
• Treatment with anti-inflammatory drugs (e.g., non-steroidal anti-inflammatory drugs (NSAID), acetylsalicylic acid (ASA), prednisone) or whole-body topical steroid during the study or within four weeks before study start. Inhaled steroids are allowed. Short term oral NSAID treatment (≤ 3 days) within four weeks before study start or during the study period is allowed. Treatment of ASA is allowed for up to 1000 mg daily.
• Treatment with colchicine within 60 days of screening visit
• Known or suspected hypersensitivity to colchicine
• Treatment with glucose lowering drugs other than insulin (e.g., Glucagon Like Peptide 1 (GLP-1) receptor agonists, metformin, selective sodium glucose cotransporter-2 (SGLT2)-inhibitors) during the study period or within four weeks before study start
• Haemodialysis or peritoneal dialysis therapy (since colchicine cannot be removed by dialysis or exchange transfusion)
• Treatment with a P-glycoprotein inhibitor (e.g., azithromycin and verapamil) or a strong CYP3A4 inhibitor (e.g., clarithromycin and ritonavir)
• Intake of grapefruit juice
• Other concomitant disease or treatment that according to the investigator's assessment makes the individual unsuitable for study participation
• Alcohol/drug abuse (assessed by the investigator)

• Regarding fertile women:

  • A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
  • Sterilised or postmenopausal women (no menses for 12 months without an alternative medical cause) can be included without the human chorionic gonadotrophin (hCG)-testing during the trial period
  • Women who are pregnant, intend to become pregnant, or are breastfeeding will not be included in the study
  • Female of childbearing potential: must use highly effective contraceptives during the trial and three months after the trial. To exclude pregnancy, urine hCG tests are performed in relation to all visits (V1-V5) and to the phone call in the washout period (P2) and there will be instructions to ensure monthly testing three months after the end of the trial.
  • The following contraceptive methods are considered highly effective and thus adequate for study enrolment for females if maintained throughout the study duration and three months after the trial: Combined hormonal contraception associated with inhibition of ovulation (containing estrogen and progestogen administered oral, intravaginal or transdermal). Progestogen-only hormonal contraception associated with inhibition of ovulation (admninistered oral, injectable or implantable). Intrauterine device (IUD). Intrauterine hormone-releasing system. Bilateral tubal occlusion. Vasectomised partner. Sexual abstinence (sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject).
  • Male participants with partners of childbearing potential: must either use a condom or ensure that their partner uses a highly effective contraceptive method during the trial and six months after the trial.
• Pregnant or nursing women
• Participants unable to speak or understand Danish
• Receipt of any investigational drug within 30 days prior to visit 1
• Simultaneous participation in any other clinical intervention trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Colchicine first period, placebo second period; Colchicine daily for 4 weeks, followed by an 8-week washout period, then placebo for 4 weeks.	Drug: Colchicin 0.5 mg once daily for two weeks, then twice daily for two weeks; Colchicine treatment in the first period; Other Names: Colrefuz; Drug: Placebo once daily for two weeks, then twice daily for two weeks; Placebo treatment in the first period; Drug: Placebo once daily for two weeks, then twice daily for two weeks; Placebo treatment in the second period
Active Comparator: Placebo first period, colchicine second period; Placebo for 4 weeks followed by an 8-week washout period, then Colchicine daily for 4 weeks.	Drug: Placebo once daily for two weeks, then twice daily for two weeks; Placebo treatment in the first period; Drug: Placebo once daily for two weeks, then twice daily for two weeks; Placebo treatment in the second period; Drug: Colchicine tablet 0.5 mg once-daily for two weeks, then twice daily for two weeks; Colchicine treatment in the second period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean difference in M-value	Mean difference in insulin sensitivity is measured by the M-value (glucose infusion rate mg/kg/min) during the last 30 minutes of a 180 minutes hyperinsulinemic euglycemic clamp procedure using insulin infusion rate of 60 mU/m²/min	Four weeks of treatment comparing colchicine to placebo.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean difference in M-value	Measured in mg/m²/min. Adjusted to body surface area (BSA)	After four weeks of placebo/colchicine
Mean difference in M-value (adjusted to fat free mass (FFM))	Measured in mg/kg FFM/min	After four weeks of placebo/colchicine
Mean difference in Insulin Sensitivity Index (ISI)	Glucose infusion rate / Plasma insulin in steady state	After four weeks of placebo/colchicine
Mean difference in average daily insulin dosage	Units/day. Total daily dose, short acting, long acting	During four weeks of placebo/colchicine
Fold difference in Insulin sensitivity by estimated glucose disposal rate (eGDR)	Ratio. It is calculated using clinical variables such as waist circumference, hypertension status, and HbA1c. Higher eGDR values indicate better insulin sensitivity	After four weeks of placebo/colchicine
Fold difference in fasting serum/plasma concentrations of C-reactive protein (CRP) measured by a high-sensitivity assay (hsCRP) (mg/L)	Ratio	After four weeks of placebo/colchicine
Fold difference in in fasting serum/plasma concentrations iInterleukin 6 (IL-6) (pg/mL)	Ratio	After four weeks of placebo/colchicine
Fold difference in in fasting serum/plasma concentrations of tumour necrosis factor alpha (TNF alpha)	Ratio	After four weeks of placebo/colchicine

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean difference in respiratory exchange ratio between basal state and during clamp	Ratio	After four weeks of placebo/colchicine
Adipocyte tissue biopsies	Ratio. Fold difference in Adipocyte size, Inflammation, Glucose metabolism, Extracellular matrix, Oxygen consumption, Transcriptomics, Proteomics	After four weeks of placebo/colchicine
Time spent in target blood glucose range (3.9 - 10 mmol/L) evaluated by a continous glucose monitor (CGM)	Measured in % of 24 hours.	The last 7 days of each treatment period.
Time spent in tight range (3.9 - 7.8 mmol/L) evaluated by a continous glucose monitor (CGM)	Measured in % of 24 hours.	The last 7 days of each treatment period.
Time spent in hyperglycemia level 1 (10-13.9 mmol/L) evaluated by a continous glucose monitor (CGM)	Measured in % of 24 hours.	The last 7 days of each treatment period.
Time spent in hyperglycemia level 2 (> 13.9 mmol/L) evaluated by a continous glucose monitor (CGM)	Measured in % of 24 hours.	The last 7 days of each treatment period.
Time spent in hypoglycemia level 1 (3.0-3.8 mmol/L) evaluated by a continous glucose monitor (CGM)	Measured in % of 24 hours.	The last 7 days of each treatment period.
Time spent in hypoglycemia level 2 (< 3.0 mmol/L)evaluated by a continous glucose monitor (CGM)	Measured in % of 24 hours.	The last 7 days of each treatment period.
Change in glycaemic variability assessed as coefficient of variance (CV)	%-point	The last 7 days of each treatment period.
Change in standard deviation evaluated by a continous glucose monitor (mmol/L)	%-point	The last 7 days of each treatment period.
Mean difference in Body mass index (BMI)	kg/m²	After four weeks of placebo/colchicine
Fold difference in waist-hip ratio	After four weeks of placebo/colchicine	ratio
Mean difference in waist circumference	Cm	After four weeks of placebo/colchicine
Mean difference in systolic blood pressure	mmHg	After four weeks of placebo/colchicine
Mean difference in diastolic blood pressure	mmHg	After four weeks of placebo/colchicine
Mean difference in heart rate	beats per minute	After four weeks of placebo/colchicine
Fold difference in body composition (fat-free mass, total fat mass, visceral fat mass rating and bone mass) as measured by bioimpedance	Ratio	After four weeks of placebo/colchicine
Fold difference in fasting serum/plasma concentrations of inflammatory biomarkers	Ratio. Interleukines and other cytokines	After four weeks of placebo/colchicine
Fold difference in fasting serum/plasma concentrations of total leukocyte count, including neutrophil, lymphocyte, basophil and eosinophil counts (10^9/L)	Ratio.	After four weeks of placebo/colchicine
Fold difference in fasting serum/plasma concentrations of very low-density lipoprotein (VLDL) cholesterol (mmol/L)	Ratio.	After four weeks of placebo/colchicine
Fold difference in fasting serum/plasma concentrations of hemoglobin A1c (mmol/mol)	Ratio	After four weeks of placebo/colchicine
Fold difference in fasting serum/plasma concentrations of insulin (pmol/L)	Ratio	After four weeks of placebo/colchicine
Fold difference fasting serum/plasma concentrations of C-peptide (pmol/L)	Ratio	After four weeks of placebo/colchicine
Fold difference in fasting serum/plasma concentrations of glucagon (pmol/L)	Ratio	After four weeks of placebo/colchicine
Mean difference in resting energy expenditure ratio between basal state and during clamp	Ratio. Participants undergo indirect calorimetry in the basal state and during the clamp (from 120-150 minutes)	After four weeks of placebo/colchicine
Fold difference in FibroScan®-assessed liver steatosis (dB/m)	Ratio. Measured before- and after each treatment period.	After four weeks of placebo/colchicine
Fold difference in Fatty Liver Index (FLI, range 0-100; higher scores indicate greater likelihood of fatty liver)	Ratio	After four weeks of placebo/colchicine Ratio
Fold difference in Fibrosis-4 (FIB-4) score	Ratio. The Fibrosis-4 score is a non-invasive index used to estimate liver fibrosis. It is calculated using age, aspartate aminotransferase, alanine aminotransferase, and platelet count. Scale range: Typically from 0 to greater than 3.25	After four weeks of placebo/colchicine
Fold difference in fasting coagulability as measured by thromboelastography (TEG)	Ratio. Measured before and after each treatment period.	After four weeks of placebo/colchicine
Fold difference in fasting serum/plasma concentrations of hormones during the HIE clamp	Ratio. Insulin, C-peptide and other counter-regulatory hormones	After four weeks of placebo/colchicine
Difference in rate of treatment-emergent AEs	Rate ratio	From signed consent form to last clamp day (week 16-18)
Difference in rate of serious AEs (SAEs)	Rate ratio	From signed consent form to last clamp day (week 16-18)
Difference in rate of severe hypoglycaemia (defined as hypoglycaemia with need of external assistance)	Rate ratio	From signed consent form to last clamp day (week 16-18)
Difference in rate of diabetic ketoacidosis	Rate ratio	From signed consent form to last clamp day (week 16-18)
Change in diabetes treatment satisfactory questionnaire, status version (DTSQs) (From 0 (min) to 6 (max), higher scores indicate a better outcome )	%-point	At Visit 2 (week 0), Visit 3 (week 4), Visit 4 (week 12) and Visit 5 (week 16)
Change in diabetes treatment satisfactory questionnaire, change version (DTSQc) (From -3 (min) to 3 (max), higher scores indicate a better outcome	%-point	At Visit 3 (week 4) and Visit 5 (week 16)
Change in fasting serum/plasma concentrations of hemoglobin (mmol/L)	%-point	After four weeks of placebo/colchicine
Change in fasting serum/plasma concentrations of thrombocytes (10^9/L)	%-point	After four weeks of placebo/colchicine
Change in fasting serum/plasma concentrations of albumin (g/L)	%-point	After four weeks of placebo/colchicine
Change in fasting serum/plasma concentrations of potassium (mmol/L)	%-point	After four weeks of placebo/colchicine
Change in fasting serum/plasma concentrations of sodium (mmol/L)	%-point	After four weeks of placebo/colchicine
Change in fasting serum/plasma concentrations of creatinine (umol/L)	%-point	After four weeks of placebo/colchicine
Change in fasting serum/plasma concentrations of creatine kinase (U/L)	%-point	After four weeks of placebo/colchicine
Change in fasting serum/plasma concentrations of estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2)	%-point	After four weeks of placebo/colchicine
Change in fasting serum/plasma concentrations of alanine aminotransferase (U/L)	%-point	After four weeks of placebo/colchicine
Change in fasting serum/plasma concentrations of aspartate aminotransferase (U/L)	%-point	After four weeks of placebo/colchicine
Change in fasting serum/plasma concentrations of bilirubin (umol/L)	%-point	After four weeks of placebo/colchicine
Change in fasting serum/plasma concentrations of amylase (units/L)	%-point	After four weeks of placebo/colchicine
Fold difference in fasting serum/plasma concentrations of high-density lipoprotein (HDL) cholesterol (mmol/L)	Ratio.	After four weeks of placebo/colchicine
Fold difference in fasting serum/plasma concentrations of total cholesterol (mmol/L)	Ratio.	After four weeks of placebo/colchicine
Fold difference in fasting serum/plasma concentrations of triglycerides (mmol/L)	Ratio.	After four weeks of placebo/colchicine
in fasting serum/plasma concentrations of lipoprotein (a) (mg/L)	Ratio.	After four weeks of placebo/colchicine

Collaborators and Investigators

• Sponsor: Asger Lund, MD
• Collaborators: University of Copenhagen
• Investigators: Principal Investigator: Asger B Lund, MD, PhD, Center for Clinical Metabolic Research, Gentofte Hospital, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2025
• Primary Completion (Estimated): December 22, 2026
• Study Completion (Estimated): June 22, 2027

Study Registration Dates

• First Submitted: September 29, 2025
• First Submitted That Met QC Criteria: November 20, 2025
• First Posted (Estimated): November 25, 2025

Study Record Updates

• Last Update Posted (Actual): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 22, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Hyperinsulinism; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 1; Insulin Resistance; Heterocyclic Compounds; Alkaloids; Colchicine
• Other Study ID Numbers: 2025-522528-29-00

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: At this stage, no final decision has been made regarding the sharing of individual participant data (IPD). While sharing de-identified data may contribute to transparency, reproducibility, and collaborative progress in type 1 diabetes and metabolic research, several factors must be considered. These include ethical and legal obligations related to participant confidentiality, the need for appropriate data-use agreements, and institutional policies on data governance. The possibility of sharing IPD will be revisited upon study completion, in alignment with ethical approvals, and journal publication policies.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No