PMID- 38096190
OWN - NLM
STAT- MEDLINE
DCOM- 20231216
LR  - 20231216
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 18
IP  - 12
DP  - 2023
TI  - Testing a new platform to screen disease-modifying therapy in type 1 diabetes.
PG  - e0293268
LID - 10.1371/journal.pone.0293268 [doi]
LID - e0293268
AB  - Studies of new therapies to preserve insulin secretion in early type 1 diabetes 
      require several years to recruit eligible subjects and to see a treatment effect; 
      thus, there is interest in alternative study designs to speed this process. Most 
      people with longstanding type 1 diabetes no longer secrete insulin. However, 
      studies from pancreata of those with longstanding T1D show that beta cells 
      staining for insulin can persist for decades after diagnosis, and this is 
      paralleled in work showing proinsulin secretion in individuals with longstanding 
      disease; collectively this suggests that there is a reserve of alive but 
      "sleeping" beta cells. Here, we designed a novel clinical trial platform to test 
      whether a short course of therapy with an agent known to have effects in type 1 
      diabetes with residual endogenous insulin could transiently induce insulin 
      secretion in those who no longer produce insulin. A therapy that transiently 
      "wakes up" sleeping beta cells might be tested next in a fully powered trial in 
      those with endogenous insulin secretion. In this three-arm non-randomized pilot 
      study, we tested three therapies known to impact disease: two beta-cell 
      supportive agents, liraglutide and verapamil, and an immunomodulatory agent, 
      golimumab. The golimumab treated arm was not fully enrolled due to uncertainties 
      about immunotherapy during the COVID-19 pandemic. Participants had mixed-meal 
      tolerance test (MMTT)-stimulated C-peptide below the quantitation limit (<0.02 
      ng/mL) at enrollment and received 8 to 12 weeks of therapy. At the completion of 
      therapy, none of the individuals achieved the primary outcome of MMTT-stimulated 
      C-peptide >/= 0.02 ng/mL. An exploratory outcome of the verapamil arm was 
      MRI-assessed pancreas size, diffusion, and longitudinal relaxation time, which 
      showed repeatability of these measures but no treatment effect. The liraglutide 
      and golimumab arms were registered on clinicaltrials.gov under accession number 
      NCT03632759 and the verapamil arm under accession number NCT05847413. Trail 
      registration: Protocols are registered in ClinicalTrials.gov under accession 
      numbers NCT03632759 and NCT05847413.
CI  - Copyright: (c) 2023 Lord et al. This is an open access article distributed under 
      the terms of the Creative Commons Attribution License, which permits unrestricted 
      use, distribution, and reproduction in any medium, provided the original author 
      and source are credited.
FAU - Lord, Sandra M
AU  - Lord SM
AUID- ORCID: 0000-0003-3508-0402
AD  - Center for Interventional Immunology, Benaroya Research Institute at Virginia 
      Mason, Seattle, WA, United States of America.
FAU - Bahnson, Henry T
AU  - Bahnson HT
AD  - Center for Interventional Immunology, Benaroya Research Institute at Virginia 
      Mason, Seattle, WA, United States of America.
FAU - Greenbaum, Carla J
AU  - Greenbaum CJ
AD  - Center for Interventional Immunology, Benaroya Research Institute at Virginia 
      Mason, Seattle, WA, United States of America.
FAU - Liljenquist, David R
AU  - Liljenquist DR
AD  - Rocky Mountain Diabetes Center, Idaho Falls, ID, United States of America.
FAU - Virostko, John
AU  - Virostko J
AUID- ORCID: 0000-0003-3413-8801
AD  - Dell Medical School, University of Texas at Austin, Austin, TX, United States of 
      America.
FAU - Speake, Cate
AU  - Speake C
AUID- ORCID: 0000-0003-1480-4272
AD  - Center for Interventional Immunology, Benaroya Research Institute at Virginia 
      Mason, Seattle, WA, United States of America.
LA  - eng
SI  - ClinicalTrials.gov/NCT03632759
SI  - ClinicalTrials.gov/NCT05847413
PT  - Journal Article
DEP - 20231214
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (C-Peptide)
RN  - 839I73S42A (Liraglutide)
RN  - 0 (Insulin)
RN  - CJ0O37KU29 (Verapamil)
SB  - IM
MH  - Humans
MH  - *Diabetes Mellitus, Type 1/drug therapy
MH  - C-Peptide
MH  - Liraglutide
MH  - Pilot Projects
MH  - Pandemics
MH  - Insulin/therapeutic use
MH  - Verapamil
PMC - PMC10721089
COIS- We have read the journal's policy and the authors of this manuscript have the 
      following competing interests: CS participates on an advisory board for Vertex 
      Pharmaceuticals. This does not alter our adherence to PLOS ONE policies on 
      sharing data and materials.
EDAT- 2023/12/14 18:43
MHDA- 2023/12/17 16:21
PMCR- 2023/12/14
CRDT- 2023/12/14 13:44
PHST- 2023/05/19 00:00 [received]
PHST- 2023/10/06 00:00 [accepted]
PHST- 2023/12/17 16:21 [medline]
PHST- 2023/12/14 18:43 [pubmed]
PHST- 2023/12/14 13:44 [entrez]
PHST- 2023/12/14 00:00 [pmc-release]
AID - PONE-D-23-14158 [pii]
AID - 10.1371/journal.pone.0293268 [doi]
PST - epublish
SO  - PLoS One. 2023 Dec 14;18(12):e0293268. doi: 10.1371/journal.pone.0293268. 
      eCollection 2023.