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Phase II multicentre, double-blind, randomised trial of ustekinumab in adolescents with new-onset type 1 diabetes (USTEK1D): trial protocol
BMJ Open, Volume: 11, Issue: 10, Start page: e049595
Swansea University Authors:
Kym Carter , Ivy Cheung, Gail Holland
, Steve Luzio
, Gareth Dunseath
, Nadim Bashir, Hayley Hutchings
, Greg Fegan, Steve Hiles
-
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DOI (Published version): 10.1136/bmjopen-2021-049595
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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<?xml version="1.0"?><rfc1807><datestamp>2021-11-17T13:27:30.1236513</datestamp><bib-version>v2</bib-version><id>58417</id><entry>2021-10-20</entry><title>Phase II multicentre, double-blind, randomised trial of ustekinumab in adolescents with new-onset type 1 diabetes (USTEK1D): trial protocol</title><swanseaauthors><author><sid>1b1870c5c1ec66eed0bf209e50a6ee25</sid><ORCID>0000-0003-0691-6282</ORCID><firstname>Kym</firstname><surname>Carter</surname><name>Kym Carter</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>a9142ffd398f89eff40ada503e315639</sid><firstname>Ivy</firstname><surname>Cheung</surname><name>Ivy Cheung</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>b9f3a8bf7478db012c8856b7bbbc7597</sid><ORCID>0000-0002-6924-2521</ORCID><firstname>Gail</firstname><surname>Holland</surname><name>Gail Holland</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>01491e1cd582746a654fad9addf0de16</sid><ORCID>0000-0002-7206-6530</ORCID><firstname>Steve</firstname><surname>Luzio</surname><name>Steve Luzio</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>fccbba9edcaee08a839a3c5cff8cbe19</sid><ORCID>0000-0001-6022-862X</ORCID><firstname>Gareth</firstname><surname>Dunseath</surname><name>Gareth Dunseath</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>c122102db1b11ced54987fb408dff69d</sid><ORCID/><firstname>Nadim</firstname><surname>Bashir</surname><name>Nadim Bashir</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>bdf5d5f154d339dd92bb25884b7c3652</sid><ORCID>0000-0003-4155-1741</ORCID><firstname>Hayley</firstname><surname>Hutchings</surname><name>Hayley Hutchings</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>a9005418b89918776f3d8895ba42e850</sid><firstname>Greg</firstname><surname>Fegan</surname><name>Greg Fegan</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>5ecd70f8c0f27219f84a7f297d99b22b</sid><firstname>Steve</firstname><surname>Hiles</surname><name>Steve Hiles</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2021-10-20</date><deptcode>HDAT</deptcode><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 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.</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">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - 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><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>© Author(s) (or their employer(s)) 2021. 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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 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 Faculty of Medicine, Health and Life Sciences 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 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 |
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BMJ Open |
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e049595 |
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2021 |
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Swansea University |
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2044-6055 2044-6055 |
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10.1136/bmjopen-2021-049595 |
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BMJ |
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Faculty of Medicine, Health and Life Sciences |
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Faculty of Medicine, Health and Life Sciences |
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Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine |
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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 |
2021-10-18T04:14:56Z |
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11.021648 |