Evidence map›Paper›PMID 26646829›Full record

ArticleBMJ open2015

Protocol of the adaptive study of IL-2 dose frequency on regulatory T cells in type 1 diabetes (DILfrequency): a mechanistic, non-randomised, repeat dose, open-label, response-adaptive study.

Lucy A Truman, Marcin L Pekalski, Paula Kareclas, Marina Evangelou, Neil M Walker, James Howlett, Adrian P Mander, Jane Kennet, Linda S Wicker, Simon Bond and 2 more

Registry-linked trialOpen access · goldAbstract readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in BMJ open, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02265809 (Adaptive Study of IL-2 Dose Frequency on Regulatory T Cells in Type 1 Diabetes), which is not on this map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.7field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02265809 phase1 / phase2completednot on this map

Adaptive Study of IL-2 Dose Frequency on Regulatory T Cells in Type 1 Diabetes (DILfrequency)

TypeinterventionalSponsorCambridge University Hospitals NHS Foundation TrustRan2014 to 2016Enrolled41ConditionsType 1 DiabetesArmsAldesleukin
3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 22 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Low-dose IL-2 reduces IL-21Nature communications · 2022
    Article
  5. Review
  6. Review
  7. Review
  8. Challenges to Reshape the Future of Type 1 Diabetes Research.The Journal of clinical endocrinology and metabolism · 2018
    Review
  9. Review
  10. Article
  11. Restoring Regulatory T Cells in Type 1 Diabetes.Current diabetes reports · 2016
    Review
  12. Review
  13. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 1 country.

Lucy A TrumanJDRF/Wellcome Trust Diabetes and Inflammation Laboratory, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK.
Marcin L PekalskiJDRF/Wellcome Trust Diabetes and Inflammation Laboratory, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK.
Paula KareclasNational Institute for Health Research Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK.
Marina EvangelouJDRF/Wellcome Trust Diabetes and Inflammation Laboratory, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK Department of Mathematics, Imperial College, London, UK.
Neil M WalkerJDRF/Wellcome Trust Diabetes and Inflammation Laboratory, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK.
James HowlettNational Institute for Health Research Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK MRC Biostatistics Unit Hub for Trials Methodology Research, Cambridge Institute of Public Health, Cambridge, UK.
Adrian P ManderMRC Biostatistics Unit Hub for Trials Methodology Research, Cambridge Institute of Public Health, Cambridge, UK.
Jane KennetJDRF/Wellcome Trust Diabetes and Inflammation Laboratory, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK.
Linda S WickerJDRF/Wellcome Trust Diabetes and Inflammation Laboratory, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK.
Simon BondNational Institute for Health Research Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK MRC Biostatistics Unit Hub for Trials Methodology Research, Cambridge Institute of Public Health, Cambridge, UK.
John A ToddJDRF/Wellcome Trust Diabetes and Inflammation Laboratory, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK.
Frank Waldron-LynchJDRF/Wellcome Trust Diabetes and Inflammation Laboratory, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK.
National Institute for Health Research · GBUniversity of Cambridge · GBWellcome Trust · GBCambridge University Hospitals NHS Foundation Trust · GBImperial College London · GBMRC Biostatistics Unit · GB

Funding

Medical Research Council G0800860Wellcome TrustWellcome Trust 091157Wellcome Trust 100140
6 · The paper itself

Abstract

introductionType 1 diabetes (T1D) is caused by autoimmune destruction of the insulin-producing β cells in the pancreatic islets, leading to insulinopenia and hyperglycaemia. Genetic analyses indicate that alterations of the interleukin-2 (IL-2) pathway mediating immune activation and tolerance predispose to T1D, specifically the polymorphic expression of the IL-2 receptor-α chain (CD25) on T lymphocytes. Replacement of physiological doses of IL-2 could restore self-tolerance and prevent further autoimmunity by enhancing the function of CD4(+) T regulatory cells (Tregs) to limit the activation of auto reactive T effector cells (Teffs). In this experimental medicine study, we use an adaptive trial design to determine the optimal dosing regimen for IL-2 to improve Treg function while limiting activation of Teffs in participants with T1D. METHODS AND ANALYSIS: The Adaptive study of IL-2 dose frequency on Tregs in type 1 diabetes(DILfrequency) is a mechanistic, non-randomised, repeat dose open-label, response-adaptive study of 36 participants with T1D. The objective is to establish the optimal dose and frequency of ultra-low dose IL-2: to increase Treg frequency within the physiological range, to increase CD25 expression on Tregs, without increasing CD4(+) Teffs. DILfrequency has an initial learning phase where 12 participants are allocated to six different doses and frequencies followed by an interim statistical analysis. After analysis of the learning phase, the Dose and Frequency Committee will select the optimal targets for Treg frequency, Treg CD25 expression and Teff frequency. Three groups of eight participants will be treated consecutively in the confirming phase. Each dose and frequency selected will be based on statistical analysis of all data collected from the previous groups. ETHICS: Ethical approval for DILfrequency was granted on 12 August 2014.

resultsThe results of this study will be reported, through peer-reviewed journals, conference presentations and an internal organisational report. TRIAL REGISTRATION NUMBERS: NCT02265809, ISRCTN40319192, CRN17571.

Indexed as

AdolescentAdultAgedClinical Trials, Phase I as TopicClinical Trials, Phase II as TopicDiabetes Mellitus, Type 1FemaleHumansInterleukin-2Interleukin-2 Receptor alpha SubunitMaleMiddle AgedNon-Randomized Controlled Trials as TopicT-Lymphocytes, RegulatoryYoung AdultInterleukin-2Interleukin-2 Receptor alpha SubunitDIABETES & ENDOCRINOLOGYGENETICSIMMUNOLOGY

Identifiers

PMID26646829
PMCPMC4679899
OpenAlexW2277210590

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.