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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.

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cam.depositDate2021-12-13
cam.issuedOnline2021-12-07
dc.contributor.authorWilhelm-Benartzi, Charlotte S
dc.contributor.authorMiller, Sarah E
dc.contributor.authorBruggraber, Sylvaine
dc.contributor.authorPicton, Diane
dc.contributor.authorWilson, Mark
dc.contributor.authorGatley, Katrina
dc.contributor.authorChhabra, Anita
dc.contributor.authorMarcovecchio, M Loredana
dc.contributor.authorHendriks, A Emile J
dc.contributor.authorMorobé, Hilde
dc.contributor.authorChmura, Piotr Jaroslaw
dc.contributor.authorBond, Simon
dc.contributor.authorAschemeier-Fuchs, Bärbel
dc.contributor.authorKnip, Mikael
dc.contributor.authorTree, Timothy
dc.contributor.authorOverbergh, Lut
dc.contributor.authorPall, Jaivier
dc.contributor.authorArnaud, Olivier
dc.contributor.authorHaller, Michael J
dc.contributor.authorNitsche, Almut
dc.contributor.authorSchulte, Anke M
dc.contributor.authorMathieu, Chantal
dc.contributor.authorMander, Adrian
dc.contributor.authorDunger, David
dc.contributor.orcidWilhelm-Benartzi, Charlotte S [0000-0003-4927-6158]
dc.contributor.orcidDunger, David [0000-0002-2566-9304]
dc.date.accessioned2021-12-14T00:31:30Z
dc.date.available2021-12-14T00:31:30Z
dc.date.issued2021-12-07
dc.date.updated2021-12-13T08:17:30Z
dc.description.abstractINTRODUCTION: Type 1 diabetes (T1D) is a chronic autoimmune disease, characterised by progressive destruction of the insulin-producing β 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 Type 1 diabetes consortium) grant agreement (www.innodia.eu). TRIAL REGISTRATION NUMBER: NCT03936634; Pre-results.
dc.identifier.doi10.17863/CAM.78832
dc.identifier.eissn2044-6055
dc.identifier.issn2044-6055
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331381
dc.language.isoeng
dc.publisherBMJ
dc.publisher.departmentDepartment of Paediatrics
dc.publisher.urlhttp://dx.doi.org/10.1136/bmjopen-2021-053669
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectgeneral diabetes
dc.subjectpaediatric endocrinology
dc.subjectstatistics & research methods
dc.subjectAdolescent
dc.subjectAdult
dc.subjectAntilymphocyte Serum
dc.subjectBlood Glucose
dc.subjectBlood Glucose Self-Monitoring
dc.subjectChild
dc.subjectClinical Trials, Phase II as Topic
dc.subjectDiabetes Mellitus, Type 1
dc.subjectHumans
dc.subjectMiddle Aged
dc.subjectMulticenter Studies as Topic
dc.subjectRandomized Controlled Trials as Topic
dc.subjectThymocytes
dc.subjectTreatment Outcome
dc.subjectYoung Adult
dc.titleStudy 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.
dc.typeArticle
prism.issueIdentifier12
prism.publicationDate2021
prism.publicationNameBMJ Open
prism.startingPagee053669
prism.volume11
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Societal Challenges (115797 INNODIA)
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
pubs.licence-identifierapollo-deposit-licence-2-1
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1136/bmjopen-2021-053669

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