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Phase II multicentre, double-blind, randomised trial of ustekinumab in adolescents with new-onset type 1 diabetes (USTEK1D): trial protocol

John W Gregory, Kym Carter Orcid Logo, Ivy Cheung, Gail Holland Orcid Logo, Jane Bowen-Morris, Steve Luzio Orcid Logo, Gareth Dunseath Orcid Logo, Timothy Tree, Jennie Hsiu Mien Yang, Ashish Marwaha, Mohammad Alhadj Ali, Nadim Bashir, Hayley Hutchings Orcid Logo, Greg Fegan Orcid Logo, Rachel Stenson, Steve Hiles, Susie Marques-Jones, Amy Brown, Danijela Tatovic, Colin Dayan

BMJ Open, Volume: 11, Issue: 10, Start page: e049595

Swansea University Authors: Kym Carter Orcid Logo, Ivy Cheung, Gail Holland Orcid Logo, Steve Luzio Orcid Logo, Gareth Dunseath Orcid Logo, Nadim Bashir, Hayley Hutchings Orcid Logo, Greg Fegan Orcid Logo, Steve Hiles

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Abstract

Introduction Most individuals newly diagnosed with type 1 diabetes (T1D) have 10%–20% of beta-cell function remaining at the time of diagnosis. Preservation of residual beta-cell function at diagnosis may improve glycaemic control and reduce longer-term complications.Immunotherapy has the potential...

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Published in: BMJ Open
ISSN: 2044-6055 2044-6055
Published: BMJ 2021
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Preservation of residual beta-cell function at diagnosis may improve glycaemic control and reduce longer-term complications.Immunotherapy has the potential to preserve endogenous beta-cell function and thereby improve metabolic control even in poorly compliant individuals. We propose to test ustekinumab (STELARA), a targeted and well-tolerated therapy that may halt T-cell and cytokine-mediated destruction of beta-cells in the pancreas at the time of diagnosis.Methods and analysis This is a double-blind phase II study to assess the safety and efficacy of ustekinumab in 72 children and adolescents aged 12&#x2013;18 with new-onset T1D.Participants should have evidence of residual functioning beta-cells (serum C-peptide level &gt;0.2nmol/L in the mixed-meal tolerance test (MMTT) and be positive for at least one islet autoantibody (GAD, IA-2, ZnT8) to be eligible.Participants will be given ustekinumab/placebo subcutaneously at weeks 0, 4 and 12, 20, 28, 36 and 44 in a dose depending on the body weight and will be followed for 12 months after dose 1.MMTTs will be used to measure the efficacy of ustekinumab for preserving C-peptide area under the curve at week 52 compared with placebo. Secondary objectives include further investigations into the efficacy and safety of ustekinumab, patient and parent questionnaires, alternative methods for measuring insulin production and exploratory mechanistic work.</abstract><type>Journal Article</type><journal>BMJ Open</journal><volume>11</volume><journalNumber>10</journalNumber><paginationStart>e049595</paginationStart><paginationEnd/><publisher>BMJ</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>2044-6055</issnPrint><issnElectronic>2044-6055</issnElectronic><keywords/><publishedDay>18</publishedDay><publishedMonth>10</publishedMonth><publishedYear>2021</publishedYear><publishedDate>2021-10-18</publishedDate><doi>10.1136/bmjopen-2021-049595</doi><url/><notes/><college>COLLEGE NANME</college><department>Health Data Science</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>HDAT</DepartmentCode><institution>Swansea University</institution><apcterm>External research funder(s) paid the OA fee (includes OA grants disbursed by the Library)</apcterm><funders>This project (project reference 16/36/01) is funded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership.</funders><lastEdited>2021-11-17T13:27:30.1236513</lastEdited><Created>2021-10-20T10:08:48.8064193</Created><path><level id="1">Swansea University Medical School</level><level id="2">Medicine</level></path><authors><author><firstname>John W</firstname><surname>Gregory</surname><order>1</order></author><author><firstname>Kym</firstname><surname>Carter</surname><orcid>0000-0003-0691-6282</orcid><order>2</order></author><author><firstname>Ivy</firstname><surname>Cheung</surname><order>3</order></author><author><firstname>Gail</firstname><surname>Holland</surname><orcid>0000-0002-6924-2521</orcid><order>4</order></author><author><firstname>Jane</firstname><surname>Bowen-Morris</surname><order>5</order></author><author><firstname>Steve</firstname><surname>Luzio</surname><orcid>0000-0002-7206-6530</orcid><order>6</order></author><author><firstname>Gareth</firstname><surname>Dunseath</surname><orcid>0000-0001-6022-862X</orcid><order>7</order></author><author><firstname>Timothy</firstname><surname>Tree</surname><order>8</order></author><author><firstname>Jennie Hsiu Mien</firstname><surname>Yang</surname><order>9</order></author><author><firstname>Ashish</firstname><surname>Marwaha</surname><order>10</order></author><author><firstname>Mohammad Alhadj</firstname><surname>Ali</surname><order>11</order></author><author><firstname>Nadim</firstname><surname>Bashir</surname><orcid/><order>12</order></author><author><firstname>Hayley</firstname><surname>Hutchings</surname><orcid>0000-0003-4155-1741</orcid><order>13</order></author><author><firstname>Greg</firstname><surname>Fegan</surname><orcid>0000-0002-2663-2765</orcid><order>14</order></author><author><firstname>Rachel</firstname><surname>Stenson</surname><order>15</order></author><author><firstname>Steve</firstname><surname>Hiles</surname><order>16</order></author><author><firstname>Susie</firstname><surname>Marques-Jones</surname><order>17</order></author><author><firstname>Amy</firstname><surname>Brown</surname><order>18</order></author><author><firstname>Danijela</firstname><surname>Tatovic</surname><order>19</order></author><author><firstname>Colin</firstname><surname>Dayan</surname><order>20</order></author></authors><documents><document><filename>58417__21274__d037da2bcd4c44da99924701eac681ac.pdf</filename><originalFilename>e049595.full.pdf</originalFilename><uploaded>2021-10-22T10:20:18.9884515</uploaded><type>Output</type><contentLength>1127836</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><documentNotes>&#xA9; Author(s) (or their employer(s)) 2021. 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spelling 2021-11-17T13:27:30.1236513 v2 58417 2021-10-20 Phase II multicentre, double-blind, randomised trial of ustekinumab in adolescents with new-onset type 1 diabetes (USTEK1D): trial protocol 1b1870c5c1ec66eed0bf209e50a6ee25 0000-0003-0691-6282 Kym Carter Kym Carter true false a9142ffd398f89eff40ada503e315639 Ivy Cheung Ivy Cheung true false b9f3a8bf7478db012c8856b7bbbc7597 0000-0002-6924-2521 Gail Holland Gail Holland true false 01491e1cd582746a654fad9addf0de16 0000-0002-7206-6530 Steve Luzio Steve Luzio true false fccbba9edcaee08a839a3c5cff8cbe19 0000-0001-6022-862X Gareth Dunseath Gareth Dunseath true false c122102db1b11ced54987fb408dff69d Nadim Bashir Nadim Bashir true false bdf5d5f154d339dd92bb25884b7c3652 0000-0003-4155-1741 Hayley Hutchings Hayley Hutchings true false a9005418b89918776f3d8895ba42e850 0000-0002-2663-2765 Greg Fegan Greg Fegan true false 5ecd70f8c0f27219f84a7f297d99b22b Steve Hiles Steve Hiles true false 2021-10-20 HDAT Introduction Most individuals newly diagnosed with type 1 diabetes (T1D) have 10%–20% of beta-cell function remaining at the time of diagnosis. Preservation of residual beta-cell function at diagnosis may improve glycaemic control and reduce longer-term complications.Immunotherapy has the potential to preserve endogenous beta-cell function and thereby improve metabolic control even in poorly compliant individuals. We propose to test ustekinumab (STELARA), a targeted and well-tolerated therapy that may halt T-cell and cytokine-mediated destruction of beta-cells in the pancreas at the time of diagnosis.Methods and analysis This is a double-blind phase II study to assess the safety and efficacy of ustekinumab in 72 children and adolescents aged 12–18 with new-onset T1D.Participants should have evidence of residual functioning beta-cells (serum C-peptide level >0.2nmol/L in the mixed-meal tolerance test (MMTT) and be positive for at least one islet autoantibody (GAD, IA-2, ZnT8) to be eligible.Participants will be given ustekinumab/placebo subcutaneously at weeks 0, 4 and 12, 20, 28, 36 and 44 in a dose depending on the body weight and will be followed for 12 months after dose 1.MMTTs will be used to measure the efficacy of ustekinumab for preserving C-peptide area under the curve at week 52 compared with placebo. Secondary objectives include further investigations into the efficacy and safety of ustekinumab, patient and parent questionnaires, alternative methods for measuring insulin production and exploratory mechanistic work. Journal Article BMJ Open 11 10 e049595 BMJ 2044-6055 2044-6055 18 10 2021 2021-10-18 10.1136/bmjopen-2021-049595 COLLEGE NANME Health Data Science COLLEGE CODE HDAT Swansea University External research funder(s) paid the OA fee (includes OA grants disbursed by the Library) This project (project reference 16/36/01) is funded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership. 2021-11-17T13:27:30.1236513 2021-10-20T10:08:48.8064193 Swansea University Medical School Medicine John W Gregory 1 Kym Carter 0000-0003-0691-6282 2 Ivy Cheung 3 Gail Holland 0000-0002-6924-2521 4 Jane Bowen-Morris 5 Steve Luzio 0000-0002-7206-6530 6 Gareth Dunseath 0000-0001-6022-862X 7 Timothy Tree 8 Jennie Hsiu Mien Yang 9 Ashish Marwaha 10 Mohammad Alhadj Ali 11 Nadim Bashir 12 Hayley Hutchings 0000-0003-4155-1741 13 Greg Fegan 0000-0002-2663-2765 14 Rachel Stenson 15 Steve Hiles 16 Susie Marques-Jones 17 Amy Brown 18 Danijela Tatovic 19 Colin Dayan 20 58417__21274__d037da2bcd4c44da99924701eac681ac.pdf e049595.full.pdf 2021-10-22T10:20:18.9884515 Output 1127836 application/pdf Version of Record true © Author(s) (or their employer(s)) 2021. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license true eng https://creativecommons.org/licenses/by/4.0/
title Phase II multicentre, double-blind, randomised trial of ustekinumab in adolescents with new-onset type 1 diabetes (USTEK1D): trial protocol
spellingShingle Phase II multicentre, double-blind, randomised trial of ustekinumab in adolescents with new-onset type 1 diabetes (USTEK1D): trial protocol
Kym Carter
Ivy Cheung
Gail Holland
Steve Luzio
Gareth Dunseath
Nadim Bashir
Hayley Hutchings
Greg Fegan
Steve Hiles
title_short Phase II multicentre, double-blind, randomised trial of ustekinumab in adolescents with new-onset type 1 diabetes (USTEK1D): trial protocol
title_full Phase II multicentre, double-blind, randomised trial of ustekinumab in adolescents with new-onset type 1 diabetes (USTEK1D): trial protocol
title_fullStr Phase II multicentre, double-blind, randomised trial of ustekinumab in adolescents with new-onset type 1 diabetes (USTEK1D): trial protocol
title_full_unstemmed Phase II multicentre, double-blind, randomised trial of ustekinumab in adolescents with new-onset type 1 diabetes (USTEK1D): trial protocol
title_sort Phase II multicentre, double-blind, randomised trial of ustekinumab in adolescents with new-onset type 1 diabetes (USTEK1D): trial protocol
author_id_str_mv 1b1870c5c1ec66eed0bf209e50a6ee25
a9142ffd398f89eff40ada503e315639
b9f3a8bf7478db012c8856b7bbbc7597
01491e1cd582746a654fad9addf0de16
fccbba9edcaee08a839a3c5cff8cbe19
c122102db1b11ced54987fb408dff69d
bdf5d5f154d339dd92bb25884b7c3652
a9005418b89918776f3d8895ba42e850
5ecd70f8c0f27219f84a7f297d99b22b
author_id_fullname_str_mv 1b1870c5c1ec66eed0bf209e50a6ee25_***_Kym Carter
a9142ffd398f89eff40ada503e315639_***_Ivy Cheung
b9f3a8bf7478db012c8856b7bbbc7597_***_Gail Holland
01491e1cd582746a654fad9addf0de16_***_Steve Luzio
fccbba9edcaee08a839a3c5cff8cbe19_***_Gareth Dunseath
c122102db1b11ced54987fb408dff69d_***_Nadim Bashir
bdf5d5f154d339dd92bb25884b7c3652_***_Hayley Hutchings
a9005418b89918776f3d8895ba42e850_***_Greg Fegan
5ecd70f8c0f27219f84a7f297d99b22b_***_Steve Hiles
author Kym Carter
Ivy Cheung
Gail Holland
Steve Luzio
Gareth Dunseath
Nadim Bashir
Hayley Hutchings
Greg Fegan
Steve Hiles
author2 John W Gregory
Kym Carter
Ivy Cheung
Gail Holland
Jane Bowen-Morris
Steve Luzio
Gareth Dunseath
Timothy Tree
Jennie Hsiu Mien Yang
Ashish Marwaha
Mohammad Alhadj Ali
Nadim Bashir
Hayley Hutchings
Greg Fegan
Rachel Stenson
Steve Hiles
Susie Marques-Jones
Amy Brown
Danijela Tatovic
Colin Dayan
format Journal article
container_title BMJ Open
container_volume 11
container_issue 10
container_start_page e049595
publishDate 2021
institution Swansea University
issn 2044-6055
2044-6055
doi_str_mv 10.1136/bmjopen-2021-049595
publisher BMJ
college_str Swansea University Medical School
hierarchytype
hierarchy_top_id swanseauniversitymedicalschool
hierarchy_top_title Swansea University Medical School
hierarchy_parent_id swanseauniversitymedicalschool
hierarchy_parent_title Swansea University Medical School
department_str Medicine{{{_:::_}}}Swansea University Medical School{{{_:::_}}}Medicine
document_store_str 1
active_str 0
description Introduction Most individuals newly diagnosed with type 1 diabetes (T1D) have 10%–20% of beta-cell function remaining at the time of diagnosis. Preservation of residual beta-cell function at diagnosis may improve glycaemic control and reduce longer-term complications.Immunotherapy has the potential to preserve endogenous beta-cell function and thereby improve metabolic control even in poorly compliant individuals. We propose to test ustekinumab (STELARA), a targeted and well-tolerated therapy that may halt T-cell and cytokine-mediated destruction of beta-cells in the pancreas at the time of diagnosis.Methods and analysis This is a double-blind phase II study to assess the safety and efficacy of ustekinumab in 72 children and adolescents aged 12–18 with new-onset T1D.Participants should have evidence of residual functioning beta-cells (serum C-peptide level >0.2nmol/L in the mixed-meal tolerance test (MMTT) and be positive for at least one islet autoantibody (GAD, IA-2, ZnT8) to be eligible.Participants will be given ustekinumab/placebo subcutaneously at weeks 0, 4 and 12, 20, 28, 36 and 44 in a dose depending on the body weight and will be followed for 12 months after dose 1.MMTTs will be used to measure the efficacy of ustekinumab for preserving C-peptide area under the curve at week 52 compared with placebo. Secondary objectives include further investigations into the efficacy and safety of ustekinumab, patient and parent questionnaires, alternative methods for measuring insulin production and exploratory mechanistic work.
published_date 2021-10-18T04:15:06Z
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