Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD): a phase 2, multicentre, double-blind, randomized, placebo-controlled trial
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, preclinic...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
F1000 Research Ltd
2020
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| _version_ | 1797055003530100736 |
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| author | Marcovecchio, ML Wicker, LS Dunger, DB Dutton, SJ Kopijasz, S Scudder, C Todd, JA Johnson, PRV |
| author_facet | Marcovecchio, ML Wicker, LS Dunger, DB Dutton, SJ Kopijasz, S Scudder, C Todd, JA Johnson, PRV |
| author_sort | Marcovecchio, ML |
| collection | OXFORD |
| description | 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) |
| first_indexed | 2024-03-06T19:05:19Z |
| format | Journal article |
| id | oxford-uuid:14ed5607-4214-4da1-af7f-42ce98f5bc00 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:05:19Z |
| publishDate | 2020 |
| publisher | F1000 Research Ltd |
| record_format | dspace |
| spelling | oxford-uuid:14ed5607-4214-4da1-af7f-42ce98f5bc002022-03-26T10:22:35ZInterleukin-2 Therapy of Autoimmunity in Diabetes (ITAD): a phase 2, multicentre, double-blind, randomized, placebo-controlled trial Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:14ed5607-4214-4da1-af7f-42ce98f5bc00EnglishSymplectic ElementsF1000 Research Ltd2020Marcovecchio, MLWicker, LSDunger, DBDutton, SJKopijasz, SScudder, CTodd, JAJohnson, PRVType 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) |
| spellingShingle | Marcovecchio, ML Wicker, LS Dunger, DB Dutton, SJ Kopijasz, S Scudder, C Todd, JA Johnson, PRV Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD): a phase 2, multicentre, double-blind, randomized, placebo-controlled trial |
| title | Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD): a phase 2, multicentre, double-blind, randomized, placebo-controlled trial |
| title_full | Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD): a phase 2, multicentre, double-blind, randomized, placebo-controlled trial |
| title_fullStr | Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD): a phase 2, multicentre, double-blind, randomized, placebo-controlled trial |
| title_full_unstemmed | Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD): a phase 2, multicentre, double-blind, randomized, placebo-controlled trial |
| title_short | Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD): a phase 2, multicentre, double-blind, randomized, placebo-controlled trial |
| title_sort | interleukin 2 therapy of autoimmunity in diabetes itad a phase 2 multicentre double blind randomized placebo controlled trial |
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