Trial reportDiabetes2012
Rapamycin/IL-2 combination therapy in patients with type 1 diabetes augments Tregs yet transiently impairs β-cell function.
Trial report in Diabetes, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00525889 (A Phase I Trial of Proleukin and Rapamune in Recent-onset Type 1 Diabetes Mellitus), which is not on this map. Cited by 197 papers, 1 of them a synthesis that pooled 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.
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.
A Phase I Trial of Proleukin and Rapamune in Recent-onset Type 1 Diabetes Mellitus (ITN018AI)
Who cites it
197 citing papers in PubMed, 1 synthesis or guideline pooled it, 307 citations in OpenAlex.
- Immune checkpoint inhibitors and type 1 diabetes mellitus: a case report and systematic review.European journal of endocrinology · 2019Pooled it
- Trial
- Exhausted-like CD8+ T cell phenotypes linked to C-peptide preservation in alefacept-treated T1D subjects.JCI insight · 2021Trial
- 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
- Immunomodulatory activity of humanized anti-IL-7R monoclonal antibody RN168 in subjects with type 1 diabetes.JCI insight · 2019Trial
- The DILfrequency study is an adaptive trial to identify optimal IL-2 dosing in patients with type 1 diabetes.JCI insight · 2018Trial
- Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial.PLoS medicine · 2016Trial
- Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients.The Journal of clinical investigation · 2015Trial
- Low-dose interleukin-2 fosters a dose-dependent regulatory T cell tuned milieu in T1D patients.Journal of autoimmunity · 2015Trial
- Anti-thymocyte globulin/G-CSF treatment preserves β cell function in patients with established type 1 diabetes.The Journal of clinical investigation · 2015Trial
- Trial
- Antithymocyte globulin treatment for patients with recent-onset type 1 diabetes: 12-month results of a randomised, placebo-controlled, phase 2 trial.The lancet. Diabetes & endocrinology · 2013Trial
- Metabolic switch: lymphocytes and the onset of T-cell-mediated autoimmunity.Cellular & molecular immunology · 2026Review
- Cytokine-independent activation of STAT5 promotes the persistence and function of CD4Molecular therapy. Advances · 2026Article
- Regulatory T cell induction strategies and applications in the treatment of immune and non-immune diseases.Signal transduction and targeted therapy · 2026Review
- Review
- Regulatory T cells in cancer and inflammation.Signal transduction and targeted therapy · 2026Review
- New and emerging therapies in type 1 diabetes mellitus.The Journal of clinical investigation · 2026Review
- Artificial intelligence in immunotherapy: revolutionizing diagnostic and therapeutic applications in cancer and autoimmune diseases.Clinical and experimental medicine · 2026Review
- Toward Disease-Modifying Therapies in Type 1 Diabetes: Focus on Teplizumab.Diabetes care · 2026Review
137 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 9 institutions in 1 country.
Funding
Abstract
Rapamycin/interleukin-2 (IL-2) combination treatment of NOD mice effectively treats autoimmune diabetes. We performed a phase 1 clinical trial to test the safety and immunologic effects of rapamycin/IL-2 combination therapy in type 1 diabetic (T1D) patients. Nine T1D subjects were treated with 2-4 mg/day rapamycin orally for 3 months and 4.5 × 10(6) IU IL-2 s.c. three times per week for 1 month. β-Cell function was monitored by measuring C-peptide. Immunologic changes were monitored using flow cytometry and serum analyses. Regulatory T cells (Tregs) increased within the first month of therapy, yet clinical and metabolic data demonstrated a transient worsening in all subjects. The increase in Tregs was transient, paralleling IL-2 treatment, whereas the response of Tregs to IL-2, as measured by STAT5 phosphorylation, increased and persisted after treatment. No differences were observed in effector T-cell subset frequencies, but an increase in natural killer cells and eosinophils occurred with IL-2 therapy. Rapamycin/IL-2 therapy, as given in this phase 1 study, resulted in transient β-cell dysfunction despite an increase in Tregs. Such results highlight the difficulties in translating therapies to the clinic and emphasize the importance of broadly interrogating the immune system to evaluate the effects of therapy.
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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.