PMID- 34663658
OWN - NLM
STAT- MEDLINE
DCOM- 20211102
LR  - 20211103
IS  - 2044-6055 (Electronic)
IS  - 2044-6055 (Linking)
VI  - 11
IP  - 10
DP  - 2021 Oct 18
TI  - Phase II multicentre, double-blind, randomised trial of ustekinumab in 
      adolescents with new-onset type 1 diabetes (USTEK1D): trial protocol.
PG  - e049595
LID - 10.1136/bmjopen-2021-049595 [doi]
LID - e049595
AB  - 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. ETHICS AND DISSEMINATION: 
      This trial received research ethics approval from the Wales Research Ethics 
      Committee 3 in September 2018 and began recruiting in December 2018.The results 
      will be disseminated using highly accessed, peer-reviewed medical journals and 
      presented at conferences. TRIAL REGISTRATION NUMBER: ISRCTN14274380.
CI  - (c) Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published 
      by BMJ.
FAU - Gregory, John W
AU  - Gregory JW
AUID- ORCID: 0000-0001-5189-3812
AD  - Division of Population Medicine, Cardiff University, Cardiff, South Glamorgan, 
      UK.
FAU - Carter, Kymberley
AU  - Carter K
AUID- ORCID: 0000-0003-0691-6282
AD  - Swansea Trials Unit (STU), Swansea University, Swansea, West Glamorgan, UK 
      k.carter@swansea.ac.uk.
FAU - Cheung, Wai Yee
AU  - Cheung WY
AUID- ORCID: 0000-0002-0915-9312
AD  - Diabetes Research Unit Cymru (DRUC), Swansea University, Swansea, West Glamorgan, 
      UK.
FAU - Holland, Gail
AU  - Holland G
AUID- ORCID: 0000-0002-6924-2521
AD  - Swansea Trials Unit (STU), Swansea University, Swansea, West Glamorgan, UK.
FAU - Bowen-Morris, Jane
AU  - Bowen-Morris J
AD  - Diabetes Research Group, Cardiff University, Cardiff, South Glamorgan, UK.
FAU - Luzio, Stephen
AU  - Luzio S
AUID- ORCID: 0000-0002-7206-6530
AD  - Diabetes Research Unit Cymru (DRUC), Swansea University, Swansea, West Glamorgan, 
      UK.
FAU - Dunseath, Gareth
AU  - Dunseath G
AUID- ORCID: 0000-0001-6022-862X
AD  - Diabetes Research Unit Cymru (DRUC), Swansea University, Swansea, West Glamorgan, 
      UK.
FAU - Tree, Timothy
AU  - Tree T
AUID- ORCID: 0000-0002-6973-5377
AD  - Peter Gorer Department of Immunobiology, King's College London, London, UK.
AD  - National Institute for Health Research (NIHR) Biomedical Research Center (BRC), 
      Guy's and St Thomas' NHS Foundation Trust and King's College London, London, UK.
FAU - Yang, Jennie Hsiu Mien
AU  - Yang JHM
AUID- ORCID: 0000-0001-6171-833X
AD  - Peter Gorer Department of Immunobiology, King's College London, London, UK.
AD  - National Institute for Health Research (NIHR) Biomedical Research Center (BRC), 
      Guy's and St Thomas' NHS Foundation Trust and King's College London, London, UK.
FAU - Marwaha, Ashish
AU  - Marwaha A
AUID- ORCID: 0000-0003-1234-0224
AD  - Department of Molecular Genetics, Cumming School of Medicine, The University of 
      Calgary, Calgary, Alberta, Canada.
FAU - Ali, Mohammad Alhadj
AU  - Ali MA
AD  - Diabetes Research Group, Cardiff University, Cardiff, South Glamorgan, UK.
FAU - Bashir, Nadim
AU  - Bashir N
AUID- ORCID: 0000-0003-0501-1342
AD  - Swansea Trials Unit (STU), Swansea University, Swansea, West Glamorgan, UK.
FAU - Hutchings, Hayley Anne
AU  - Hutchings HA
AUID- ORCID: 0000-0003-4155-1741
AD  - Swansea Trials Unit (STU), Swansea University, Swansea, West Glamorgan, UK.
FAU - Fegan, Greg W
AU  - Fegan GW
AUID- ORCID: 0000-0002-2663-2765
AD  - Swansea Trials Unit (STU), Swansea University, Swansea, West Glamorgan, UK.
FAU - Stenson, Rachel
AU  - Stenson R
AD  - Diabetes Research Group, Cardiff University, Cardiff, South Glamorgan, UK.
FAU - Hiles, Stephen
AU  - Hiles S
AUID- ORCID: 0000-0002-8376-4377
AD  - Swansea Trials Unit (STU), Swansea University, Swansea, West Glamorgan, UK.
FAU - Marques-Jones, Susie
AU  - Marques-Jones S
AD  - Patient and Public Representative, Ammanford, West Glamorgan, UK.
FAU - Brown, Amy
AU  - Brown A
AD  - Patient and Public Representative, Cardiff, UK.
FAU - Tatovic, Danijela
AU  - Tatovic D
AD  - Diabetes Research Group, Cardiff University, Cardiff, South Glamorgan, UK.
FAU - Dayan, Colin
AU  - Dayan C
AUID- ORCID: 0000-0002-6557-3462
AD  - Diabetes Research Group, Cardiff University, Cardiff, South Glamorgan, UK.
LA  - eng
PT  - Clinical Trial Protocol
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211018
PL  - England
TA  - BMJ Open
JT  - BMJ open
JID - 101552874
RN  - 0 (C-Peptide)
RN  - 0 (Insulin)
RN  - FU77B4U5Z0 (Ustekinumab)
SB  - IM
MH  - Adolescent
MH  - C-Peptide
MH  - Clinical Trials, Phase II as Topic
MH  - *Diabetes Mellitus, Type 1/drug therapy
MH  - Double-Blind Method
MH  - Humans
MH  - Insulin
MH  - Multicenter Studies as Topic
MH  - Randomized Controlled Trials as Topic
MH  - Treatment Outcome
MH  - *Ustekinumab/therapeutic use
PMC - PMC8524290
OTO - NOTNLM
OT  - diabetes & endocrinology
OT  - paediatric endocrinology
OT  - statistics & research methods
COIS- Competing interests: None declared.
EDAT- 2021/10/20 06:00
MHDA- 2021/11/03 06:00
PMCR- 2021/10/18
CRDT- 2021/10/19 05:54
PHST- 2021/10/19 05:54 [entrez]
PHST- 2021/10/20 06:00 [pubmed]
PHST- 2021/11/03 06:00 [medline]
PHST- 2021/10/18 00:00 [pmc-release]
AID - bmjopen-2021-049595 [pii]
AID - 10.1136/bmjopen-2021-049595 [doi]
PST - epublish
SO  - BMJ Open. 2021 Oct 18;11(10):e049595. doi: 10.1136/bmjopen-2021-049595.