Trial reportJCI insight2018
The DILfrequency study is an adaptive trial to identify optimal IL-2 dosing in patients with type 1 diabetes.
Trial report in JCI insight, 2018. 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 26 papers.
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.
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.
Adaptive Study of IL-2 Dose Frequency on Regulatory T Cells in Type 1 Diabetes (DILfrequency)
Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Low-dose IL-2 in children with recently diagnosed type 1 diabetes: a Phase I/II randomised, double-blind, placebo-controlled, dose-finding study.Diabetologia · 2020Trial
- Artificial intelligence in immunotherapy: revolutionizing diagnostic and therapeutic applications in cancer and autoimmune diseases.Clinical and experimental medicine · 2026Review
- The Role of Adaptive and Innovative Trial Designs in Diabetes Research: A Scoping Review.Diabetes care · 2026Article
- Article
- Leveraging artificial intelligence and machine learning to accelerate discovery of disease-modifying therapies in type 1 diabetes.Diabetologia · 2025Review
- Immunotherapies for prevention and treatment of type 1 diabetes.Immunotherapy · 2025Review
- The IL-2 SYNTHORIN molecule promotes functionally adapted Tregs in a preclinical model of type 1 diabetes.JCI insight · 2024Article
- Assessing the effectiveness of Interleukin-2 therapy in experimental type 1 diabetes.Endocrine · 2024Article
- The immunology of type 1 diabetes.Nature reviews. Immunology · 2024Review
- IL-2-driven CD8Trends in immunology · 2023Review
- SARS-CoV-2 infection induces a long-lived pro-inflammatory transcriptional profile.Genome medicine · 2023Article
- Prevention of Type 1 Diabetes in Children: A Worthy Challenge?International journal of environmental research and public health · 2023Review
- Low-dose IL-2 enhances the generation of IL-10-producing immunoregulatory B cells.Nature communications · 2023Article
- IL-2-based approaches to Treg enhancement.Clinical and experimental immunology · 2023Review
- Regulatory T cell adoptive transfer alters uterine immune populations, increasing a novel MHC-IIFrontiers in immunology · 2023Article
- Low-dose IL-2 reduces IL-21Nature communications · 2022Article
- Self-Antigens Targeted by Regulatory T Cells in Type 1 Diabetes.International journal of molecular sciences · 2022Review
- Guidelines for standardizing T-cell cytometry assays to link biomarkers, mechanisms, and disease outcomes in type 1 diabetes.European journal of immunology · 2022Article
- Diabetes type 1: Can it be treated as an autoimmune disorder?Reviews in endocrine & metabolic disorders · 2021Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 2 institutions in 3 countries.
Funding
Abstract
backgroundType 1 diabetes (T1D) results from loss of immune regulation, leading to the development of autoimmunity to pancreatic β cells, involving autoreactive T effector cells (Teffs). Tregs, which prevent autoimmunity, require IL-2 for maintenance of immunosuppressive functions. Using a response-adaptive design, we aimed to determine the optimal regimen of aldesleukin (recombinant human IL-2) to physiologically enhance Tregs while limiting expansion of Teffs.
methodsDILfrequency is a nonrandomized, open-label, response-adaptive study of participants, aged 18-70 years, with T1D. The initial learning phase allocated 12 participants to 6 different predefined regimens. Then, 3 cohorts of 8 participants were sequentially allocated dose frequencies, based on repeated interim analyses of all accumulated trial data. The coprimary endpoints were percentage change in Tregs and Teffs and CD25 (α subunit of the IL-2 receptor) expression by Tregs, from baseline to steady state.
resultsThirty-eight participants were enrolled, with thirty-six completing treatment. The optimal regimen to maintain a steady-state increase in Tregs of 30% and CD25 expression of 25% without Teff expansion is 0.26 × 106 IU/m2 (95% CI -0.007 to 0.485) every 3 days. Tregs and CD25 were dose-frequency responsive, Teffs were not. The commonest adverse event was injection site reaction (464 of 694 events).
conclusionsUsing a response-adaptive design, aldesleukin treatment can be optimized. Our methodology can generally be employed to immediately access proof of mechanism, thereby leading to more efficient and safe drug development.
trial registrationInternational Standard Randomised Controlled Trial Number Register, ISRCTN40319192; ClinicalTrials.gov, NCT02265809.
fundingSir Jules Thorn Trust, the Swiss National Science Foundation, Wellcome, JDRF, and NIHR Cambridge Biomedical Research Centre.
Indexed as
Identifiers
What OpenQuestion holds
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.