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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Colchicin 0.5 mg once daily for two weeks, then twice daily for two weeks
  Colchicine treatment in the first period
• Препарат Placebo once daily for two weeks, then twice daily for two weeks
  Placebo treatment in the first period
• Препарат Colchicine tablet 0.5 mg once-daily for two weeks, then twice daily for two weeks
  Colchicine treatment in the second period
• Препарат Placebo once daily for two weeks, then twice daily for two weeks
  Placebo treatment in the second period

Первичные конечные точки

• Mean difference in M-value [Срок оценки: Four weeks of treatment comparing colchicine to placebo.]

Вторичные конечные точки (8)

• Mean difference in M-value [Срок оценки: After four weeks of placebo/colchicine]
• Mean difference in M-value (adjusted to fat free mass (FFM)) [Срок оценки: After four weeks of placebo/colchicine]
• Mean difference in Insulin Sensitivity Index (ISI) [Срок оценки: After four weeks of placebo/colchicine]
• Mean difference in average daily insulin dosage [Срок оценки: During four weeks of placebo/colchicine]
• Fold difference in Insulin sensitivity by estimated glucose disposal rate (eGDR) [Срок оценки: 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) [Срок оценки: After four weeks of placebo/colchicine]
• Fold difference in in fasting serum/plasma concentrations iInterleukin 6 (IL-6) (pg/mL) [Срок оценки: After four weeks of placebo/colchicine]
• Fold difference in in fasting serum/plasma concentrations of tumour necrosis factor alpha (TNF alpha) [Срок оценки: After four weeks of placebo/colchicine]

Критерии участия

Критерии включения

• 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)\*\*

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Дания · 1 центр

• Center for Clinical Metabolic Research, Gentofte Hospital, Hellerup, Capital Region 2900 — Gentofte Municipality

Идентификаторы

NCT: NCT07247734 · 2025-522528-29-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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