Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD): a phase 2, multicentre, double-blind, randomized, placebo-controlled trial

Abstract

Type 1 diabetes is a common autoimmune disease due to destruction of pancreatic β cells, resulting in lifelong need for insulin. Evidence suggest that maintaining residual β-cell function can improve glucose control and reduce risk of hypoglycaemia and vascular complications. Non-clinical, preclinical and some preliminary clinical data suggest that low-dose interleukin-2 (IL-2) therapy could block pancreatic β cells destruction by increasing the number of functional regulatory T cells (Tregs) that inhibit islet-specific autoreactive effector T cells (Teffs). However, there is lack of data on the effect of low-dose IL-2 in newly diagnosed children and adolescents with T1D as well as lack of specific data on its potential effect on β-cell function. The ‘Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD)’ is a phase 2, multicentre, double-blind, randomised, placebo-controlled trial in children and adolescents (6-18 years; having detectable C-peptide) initiated within 6 weeks of T1D diagnosis. A total of 45 participants will be randomised in a 2:1 ratio to receive either ultra-low dose IL-2 (aldesleukin), at a dose of 0.2 x 106 IU/m2 twice-weekly, given subcutaneously, or placebo, for 6 months. The primary objective is to assess the effects of ultra-low dose aldesleukin administration on endogenous β-cell function as measured by frequent home dried blood spot (DBS) fasting and post-prandial C-peptide in children and adolescents with newly diagnosed T1D. The secondary objectives are: 1) to assess the efficacy of regular dosing of aldesleukin in increasing Treg levels; 2) to confirm the clinical safety and tolerability of ultra-low dose aldesleukin; 3) to assess changes in the immune system indicating benefit or potential risk for future gains/loss in β-cell function and immune function; 4) to assess treatment effect on glycaemic control. Trial registration: EudraCT 2017-002126-20 (06/02/2019)

Beta cell and immune cell interactions in autoimmune type 1 diabetes: How they meet and talk to each other

“…The daily administration of low-dose IL-2 for five consecutive days effectively expanded Tregs in peripheral blood, with almost no effect on effector T cells or NK cells, which was not the case with administration of higher doses. An ongoing trial (Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD)) is now assessing the effect of low-dose IL-2 on endogenous beta cell function in newly diagnosed children and adolescents (aged 6-18 y) [ 118 ].…”

Therapeutic Strategies for Diabetes: Immune Modulation in Pancreatic β Cells

“…In NOD studies, low-dose of IL-2 increased Treg population to prevent the progression of diabetes (95). Furthermore, administration of low dose of aldesleukin, a recombinant IL-2, increased the population of Treg without drug-relative adverse effects in T1D patients versus placebo (96). Currently, a phase 2 clinical trial evaluating the FIGURE 2 | Schematic view of gut microbiota dysbiosis contributing to both type 1 and type2 diabetes.…”

The Potential Mechanisms of High-Velocity, Low-Amplitude, Controlled Vertebral Thrusts on Neuroimmune Function: A Narrative Review

“…It also promotes self-tolerance and inhibits the growth of some human tumor cells [79]. IL-2 is currently being used to treat auto-immune disorders and various cancers [84][85][86]. However, there are still unanswered questions about whether this increase has a clinically relevant impact on immunity, whether a similar increase can be seen in people with various pathological conditions, how long this effect lasts, and whether it has a positive impact in patients with autoimmune conditions, or cancer patients, or whether it has an anti-inflammatory effect.…”