TY - JOUR
T1 - Phase II multicentre, double-blind, randomised trial of ustekinumab in adolescents with new-onset type 1 diabetes (USTEK1D)
T2 - Trial protocol
AU - Gregory, John W.
AU - Carter, Kymberley
AU - Cheung, Wai Yee
AU - Holland, Gail
AU - Bowen-Morris, Jane
AU - Luzio, Stephen
AU - Dunseath, Gareth
AU - Tree, Timothy
AU - Yang, Jennie Hsiu Mien
AU - Marwaha, Ashish
AU - Ali, Mohammad Alhadj
AU - Bashir, Nadim
AU - Hutchings, Hayley Anne
AU - Fegan, Greg W.
AU - Stenson, Rachel
AU - Hiles, Stephen
AU - Marques-Jones, Susie
AU - Brown, Amy
AU - Tatovic, Danijela
AU - Dayan, Colin
N1 - Funding Information:
Funding This project (project reference 16/36/01) is funded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership. Additional funding for mechanistic laboratory tests has been provided by JDRF (Juvenile Diabetes Research Foundation) International Award 3-SRA-2018–629 s-B.
Publisher Copyright:
© 2021 Author(s). Published by BMJ.
PY - 2021/10/18
Y1 - 2021/10/18
N2 - 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.
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.
KW - diabetes & endocrinology
KW - paediatric endocrinology
KW - statistics & research methods
UR - http://www.scopus.com/inward/record.url?scp=85117754491&partnerID=8YFLogxK
U2 - 10.1136/bmjopen-2021-049595
DO - 10.1136/bmjopen-2021-049595
M3 - Article
AN - SCOPUS:85117754491
SN - 2044-6055
VL - 11
JO - BMJ Open
JF - BMJ Open
IS - 10
M1 - e049595
ER -
