Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD): a phase 2, multicentre, double-blind, randomized, placebo-controlled trial
| Autor: | Susan J Dutton, John A. Todd, Linda S. Wicker, Johnson Prv., Claire Scudder, M. L. Marcovecchio, S Kopijasz, David B. Dunger |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty type 1 diabetes medicine.medical_treatment Placebo-controlled study Medicine (miscellaneous) 030209 endocrinology & metabolism Placebo General Biochemistry Genetics and Molecular Biology Study Protocol 03 medical and health sciences 0302 clinical medicine children Aldesleukin Internal medicine Diabetes mellitus medicine adolescents Autoimmune disease Type 1 diabetes business.industry Beta cells Articles Immunotherapy medicine.disease Treg 030104 developmental biology Tolerability Interleukin-2 immunotherapy aldesleukin C-peptide business |
| Zdroj: | Wellcome Open Research |
| ISSN: | 2398-502X |
| DOI: | 10.12688/wellcomeopenres.15697.1 |
| Popis: | 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) |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|