Repurposing colchicine for reduction of residual inflammatory risk in type 1 diabetes (REC1TE): a randomized, double-blind, placebo-controlled, investigator-initiated trial

The primary objective of this study is to evaluate the effect of **colchicine** on levels of high-sensitivity C-reactive protein (hs-CRP) in patients with **Type 1 diabetes** over a 26-week treatment period, compared to a placebo. This is clinically relevant as hs-CRP is a marker of inflammation, and reducing inflammation may help mitigate cardiovascular risks associated with Type 1 diabetes. The study is designed as a randomized, double-blind, placebo-controlled trial to ensure the reliability of the results.

The clinical trial involves participants diagnosed with **Type 1 diabetes** for more than five years, as per World Health Organization criteria. The study population includes both male and female subjects, aged between 18 and 80 years. Participants are required to have an HbA1c level of less than 80 mmol/mol and must be on stable insulin therapy, with no recent changes in insulin brand or initiation of continuous subcutaneous insulin infusion or multiple daily injections. Additionally, if applicable, the usage of glucose monitoring technology should be stable for at least three months. The trial also considers individuals with a **C-reactive protein** level of 2 mg/l or higher, measured by a high-sensitivity assay, and an estimated glomerular filtration rate greater than 50 ml/min/1.73 m². Participants either have stable atherosclerotic cardiovascular disease or are at high risk thereof, as defined by the European Society of Cardiology or the Steno Type 1 Diabetes Risk Engine. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the effect of **colchicine** on high-sensitivity C-reactive protein levels in individuals with type 1 diabetes. This study is a randomized, double-blind, placebo-controlled trial, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thus minimizing bias. The trial is expected to last for 26 weeks, with participants receiving either colchicine or a placebo in tablet form, administered orally. The primary objective is to assess the estimated treatment difference in high-sensitivity C-reactive protein levels between the colchicine and placebo groups after the treatment period.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as having type 1 diabetes for more than five years, being aged 18-80 years, and having stable insulin therapy. Follow-up visits will occur periodically throughout the trial to monitor safety, adherence, and efficacy endpoints, including glycated hemoglobin levels, time spent in target glycemia, and insulin dosage. The end-of-study visit will conclude the trial, where final assessments will be conducted to evaluate the primary and secondary endpoints.

The expected length of participant involvement is approximately 30 weeks, accounting for the treatment period and additional time for follow-up assessments. Conditions that may lead to early termination from the study include significant adverse events, non-compliance with the study protocol, or withdrawal of consent by the participant. The trial aims to provide valuable insights into the potential repurposing of colchicine for reducing residual inflammatory risk in type 1 diabetes, contributing to the broader understanding of managing this chronic condition.

The clinical trial involves the administration of **Colchicine**, marketed under the name Colrefuz, in tablet form. The pharmaceutical form is a coated tablet designed to be indistinguishable from the placebo. The active substance, **Colchicine**, is of chemical origin and is classified under the ATC code M04AC01. The maximum daily dose is 0.5 mg, with the same amount being the total daily dose. The treatment period extends up to 26 weeks. The route of administration is oral, and the medication is provided by ACTAVIS GROUP PTC EHF. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen.

The comparator treatment in this study is a placebo designed to match the appearance of the Colrefuz tablets. The placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The placebo is administered orally, following the same dosing schedule as the active treatment, to serve as a control for evaluating the effect of Colchicine on high-sensitivity C-reactive protein levels in participants with type 1 diabetes. The placebo is manufactured to be chemically inert, containing no active pharmaceutical ingredients.

Efficacy in the clinical trial titled "Repurposing colchicine for reduction of residual inflammatory risk in type 1 diabetes (REC1TE)" will be assessed primarily by measuring the effect of **colchicine** on levels of high-sensitivity C-reactive protein (hs-CRP) in comparison to placebo after 26 weeks of treatment. The primary endpoint is the estimated treatment difference in hs-CRP levels (mg/l) between the colchicine and placebo groups. Secondary endpoints include hs-CRP levels measured at week 30, glycated hemoglobin (mmol/mol; %-point), and various metrics related to glycemic control such as time spent in target glycemia and different levels of hyperglycemia and hypoglycemia, all assessed by continuous glucose monitoring. Additional secondary endpoints include insulin dosage (both long-acting and short-acting), body weight, waist-to-hip ratio, low-density lipoprotein cholesterol, interleukin-6, tumor necrosis factor alpha, serious adverse events, and events of severe hypoglycemia and diabetic ketoacidosis.