التفاصيل البيبلوغرافية
| العنوان: |
Study protocol : Minimum effective low dose: anti-human thymocyte globulin (MELD-ATG): phase II, dose ranging, efficacy study of antithymocyte globulin (ATG) within 6 weeks of diagnosis of type 1 diabetes |
| المؤلفون: |
Wilhelm-Benartzi, Charlotte S., Miller, Sarah E., Bruggraber, Sylvaine, Picton, Diane, Wilson, Mark, Gatley, Katrina, Chhabra, Anita, Marcovecchio, M. Loredana, Hendriks, A. Emile J., Morobe, Hilde, Chmura, Piotr Jaroslaw, Bond, Simon, Aschemeier-Fuchs, Barbel, Knip, Mikael, Tree, Timothy, Overbergh, Lut, Pall, Jaivier, Arnaud, Olivier, Haller, Michael J., Nitsche, Almut, Schulte, Anke M., Mathieu, Chantal, Mander, Adrian, Dunger, David |
| المساهمون: |
HUS Children and Adolescents, Children's Hospital, Research Programs Unit, CAMM - Research Program for Clinical and Molecular Metabolism |
| بيانات النشر: |
BMJ Publishing Group Ltd |
| سنة النشر: |
2022 |
| المجموعة: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| مصطلحات موضوعية: |
BETA-CELL FUNCTION, RECENT-ONSET, DOUBLE-BLIND, C-PEPTIDE, THERAPY, PREVALENCE, DURATION, 3121 General medicine, internal medicine and other clinical medicine |
| الوصف: |
Introduction Type 1 diabetes (T1D) is a chronic autoimmune disease, characterised by progressive destruction of the insulin-producing beta cells of the pancreas. One immunosuppressive agent that has recently shown promise in the treatment of new-onset T1D subjects aged 12-45 years is antithymocyte globulin (ATG), Thymoglobuline, encouraging further exploration in lower age groups. Methods and analysis Minimal effective low dose (MELD)-ATG is a phase 2, multicentre, randomised, double-blind, placebo-controlled, multiarm parallel-group trial in participants 5-25 years diagnosed with T1D within 3-9 weeks of planned treatment day 1. A total of 114 participants will be recruited sequentially into seven different cohorts with the first cohort of 30 participants being randomised to placebo, 2.5 mg/kg, 1.5 mg/kg, 0.5 mg/kg and 0.1 mg/kg ATG total dose in a 1:1:1:1:1 allocation ratio. The next six cohorts of 12-15 participants will be randomised to placebo, 2.5 mg/kg, and one or two selected middle ATG total doses in a 1:1:1:1 or 1:1:1 allocation ratio, as dependent on the number of middle doses, given intravenously over two consecutive days. The primary objective will be to determine the changes in stimulated C-peptide response over the first 2 hours of a mixed meal tolerance test at 12 months for 2.5 mg/kg ATG arm vs the placebo. Conditional on finding a significant difference at 2.5 mg/kg, a minimally effective dose will be sought. Secondary objectives include the determination of the effects of a particular ATG treatment dose on (1) stimulated C-peptide, (2) glycated haemoglobin, (3) daily insulin dose, (4) time in range by intermittent continuous glucose monitoring measures, (5) fasting and stimulated dry blood spot (DBS) C-peptide measurements. Ethics and dissemination MELD-ATG received first regulatory and ethical approvals in Belgium in September 2020 and from the German and UK regulators as of February 2021. The publication policy is set in the INNODIA (An innovative approach towards understanding and arresting ... |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
This clinical trial is funded by Innovative Medicine Initiative 2 Joint Undertaking (IMI2 JU) INNODIA under grant agreement no 115797. This Joint Undertaking receives support from the Union's Horizon 2020 research and innovation program and 'EFPIA', 'JDRF' and `The Leona M. and Harry B. Helmsley Charitable Trust'. The IMP is supplied by INNODIA member Sanofi. The CE-marked CGM devices are provided by DexCom (USA). supported by IMI2-JU under grant agreement No 115797 (INNODIA) and No 945268 (INNODIA HARVEST). DD was supported by the UK NIHR Cambridge Biomedical Research Centre.The sponsor is Universitaire Ziekenhuizen Leuven (UZL), Leuven, Belgium. Sponsor Number: S63466. Central Coordination is done on behalf of the sponsor by the University of Cambridge, UK (MELD-ATG@medschl.cam.ac.uk).The EudraCT Number is 2019-003265-17.; Wilhelm-Benartzi , C S , Miller , S E , Bruggraber , S , Picton , D , Wilson , M , Gatley , K , Chhabra , A , Marcovecchio , M L , Hendriks , A E J , Morobe , H , Chmura , P J , Bond , S , Aschemeier-Fuchs , B , Knip , M , Tree , T , Overbergh , L , Pall , J , Arnaud , O , Haller , M J , Nitsche , A , Schulte , A M , Mathieu , C , Mander , A & Dunger , D 2021 , ' Study protocol : Minimum effective low dose: anti-human thymocyte globulin (MELD-ATG): phase II, dose ranging, efficacy study of antithymocyte globulin (ATG) within 6 weeks of diagnosis of type 1 diabetes ' , BMJ Open , vol. 11 , no. 12 , 053669 . https://doi.org/10.1136/bmjopen-2021-053669Test; 2ea7f5a7-f008-4f85-a9ee-ab631f0269ab; http://hdl.handle.net/10138/338177Test; 000730060800005 |
| الإتاحة: |
http://hdl.handle.net/10138/338177Test |
| حقوق: |
cc_by ; openAccess ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: |
edsbas.BE8FE46F |
| قاعدة البيانات: |
BASE |
