The effect of colchicine, on insulin sensitivity in individuals with type 1 diabetes and systemic low-grade inflammation (INS1GHT)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Change in M-value after four weeks of placebo/colchicine
研究概览
简要总结
This randomised, double-blind, placebo-controlled, crossover study will investigate the effect of four weeks of colchicine adjunctive to standard care (SoC) on insulin sensitivity in persons with T1D, systemic low-grade inflammation and reduced insulin sensitivity. Colchicine is taken as a tablet of 0.5 mg once daily (OD) for two weeks followed by 0.5 mg twice daily (BID) for two weeks. Systemic low-grade inflammation is assessed by a high-sensitivity CRP (hsCRP) assay ≥2 mg/dl and insulin sensitivity is assessed by an estimated glucose disposal rate (eGDR) <8 mg/kg/min OR insulin usage of ≥1 insulin units (IU)/kg pr day. The primary aim is to evaluate the effect of colchicine on insulin sensitivity expressed as the average glucose infusion rate (M-value [mg/kg/min]) during a hyperinsulinaemic-euglycaemic (HIE) clamp as compared to placebo treatment.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •T1D for more than five years and c-peptid <200 pmol/L
- •Age 18–80 years
- •User of a CGM system
- •HbA1c 42-75 mmol/mol
- •Stable insulin therapy
- •eGFR ≥ 60 mL/min/L/1.73 m²
- •hsCRP ≥ 2 mg/L
排除标准
- •Hypoglycaemia unawareness
- •Immunosuppressive therapy or state of chronic immunodeficiency, including infection with human immunodeficiency virus (HIV)
- •Treatment with anti-inflammatory drugs
- •Treatment with colchicine within 60 days of screening visit
- •Known or suspected hypersensitivity to colchicine
- •Treatment with glucose lowering drugs other than insulin
- •Haemodialysis or peritoneal dialysis therapy
- •Treatment with a P-glycoprotein inhibitor or a strong CYP3A4 inhibitor
- •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
- •Liver disease with elevated plasma alanine aminotransferase (ALT) > three times the upper limit of normal
- •Pregnant or nursing women
- •Receipt of any investigational drug within 30 days prior to visit 1
- •Simultaneous participation in any other clinical intervention trial
- •Women of child bearing potential not using contraceptive
- •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
- •Cancer or lymphoproliferative disease unless in complete remission for > 5 years
- •Blood dyscrasias
- •Leukocyte cell count < 3.0 X 109/L
- •Thrombocyte count < 110 X 109/L
结局指标
主要结局
Change in M-value after four weeks of placebo/colchicine
Change in M-value after four weeks of placebo/colchicine
次要结局
- Mean difference in M-value (adjusted to body surface area (BSA)
- Mean difference in M-value (adjusted to fat free mass)
- Mean difference in Insulin Sensitivity Index (ISI)
- Mean difference in average daily insulin dosage
- Fold difference in Insulin sensitivity by estimated glucose disposal rate (eGDR)
- Fold difference in in fasting serum/plasma concentrations of inflammation markers hsCRP, IL-6, Tumour necrosis factor α
研究者
Center for Clinical Metabolic Research
Scientific
Gentofte Hospital