Evidence map›Paper›PMID 32651161›Full record

Trial reportEBioMedicine2020

Repeated 5-day cycles of low dose aldesleukin in amyotrophic lateral sclerosis (IMODALS): A phase 2a randomised, double-blind, placebo-controlled trial.

William Camu, Marius Mickunas, Jean-Luc Veyrune, Christine Payan, Cecilia Garlanda, Massimo Locati, Raul Juntas-Morales, Nicolas Pageot, Andrea Malaspina, Ulf Andreasson and 11 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02059759 (Immuno-modulation in Amyotrophic Lateral Sclerosis- a Phase II Study of Safety and Activity of Low Dose Interleukin-2), which is not on this map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
3.4field-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.

NCT02059759 phase2completednot on this map

Immuno-modulation in Amyotrophic Lateral Sclerosis- a Phase II Study of Safety and Activity of Low Dose Interleukin-2

TypeinterventionalSponsorCentre Hospitalier Universitaire de NīmesRan2015 to 2016Enrolled36ConditionsAmyotrophic Lateral SclerosisArmsPlacebo, 1.0 MIU IL-2 per day, 2.0 MIU IL-2 per day
3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 79 citations in OpenAlex.

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  3. Safety and efficacy of dimethyl fumarate in ALS: randomised controlled study.Annals of clinical and translational neurology · 2021
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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

21 authors at 11 institutions in 4 countries.

William CamuClinique du Motoneurone, CHU Gui de Chauliac, University of Montpellier, Montpellier, France.
Marius MickunasDepartment Immunobiology, Faculty of Life Sciences and Medicine, King's College London, London, UK; NIHR Biomedical Research Centre, Guy's and St Thomas' NHS Foundation Trust and King's College London, London, UK.
Jean-Luc VeyruneDepartment of Cell and Tisue Engineering, University of Montpellier, CHU Montpellier, Montpellier France.
Christine PayanDepartment of Biostatistics, Clinical Epidemiology, Public Health and Innovation in Methodology (BESPIM), Nîmes University Hospital, Nîmes, France; Department of Pharmacology, AP-HP.Sorbonne Université, Pitié-Salpêtrière Hospital, 47, Bd de l'Hôpital, F-75013 Paris, France.
Cecilia GarlandaIRCCS Humanitas Clinical & Research Institute, Milan, Italy; Humanitas University, Pieve Emanuele, Milan, Italy.
Massimo LocatiIRCCS Humanitas Clinical & Research Institute, Milan, Italy; Department of Medical Biotechnologies and Translational Medicine, University Milan, Milan Italy.
Raul Juntas-MoralesClinique du Motoneurone, CHU Gui de Chauliac, University of Montpellier, Montpellier, France.
Nicolas PageotClinique du Motoneurone, CHU Gui de Chauliac, University of Montpellier, Montpellier, France.
Andrea MalaspinaNeuroscience and Trauma Centre, Institute of Cell and Molecular Medicine, Department of Neuroimmunology, Barts and the London School of Medicine and Dentistry, London, UK.
Ulf AndreassonDepartment of Psychiatry & Neurochemistry, University of Gothenburg, Mölndal, Sweden.
Janine KirbySheffield Institute for Translational Neuroscience, Department of Neuroscience, University of Sheffield, Sheffield, UK.
Carey SuehsDepartments of Medical Information and Respiratory Diseases, University of Montpellier, CHU Montpellier, Montpellier, France.
Safa SakerDNA and Cell Bank, Genethon, Evry, France.
Christophe MasseguinDelegation for Clinical Research and Innovation, Nîmes University Hospital, Nîmes, France.
John De VosDepartment of Cell and Tisue Engineering, University of Montpellier, CHU Montpellier, Montpellier France.
Henrik ZetterbergDepartment of Psychiatry & Neurochemistry, University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK; UK Dementia Research Institute at UCL, London, UK.
Pamela J ShawSheffield Institute for Translational Neuroscience, Department of Neuroscience, University of Sheffield, Sheffield, UK.
Ammar Al-ChalabiInstitute of Psychiatry Psychology and Neuroscience, Department of Basic and Clinical Neuroscience, King's College London, London, UK; Department of Neurology, King's College Hospital, London, UK.
P Nigel LeighThe Trafford Centre for Biomedical Research, Brighton and Sussex Medical School, Falmer, Brighton BN1 9RY, UK.
Timothy TreeDepartment Immunobiology, Faculty of Life Sciences and Medicine, King's College London, London, UK; NIHR Biomedical Research Centre, Guy's and St Thomas' NHS Foundation Trust and King's College London, London, UK. Electronic address: timothy.tree@kcl.ac.uk.
Gilbert BensimonDepartment of Biostatistics, Clinical Epidemiology, Public Health and Innovation in Methodology (BESPIM), Nîmes University Hospital, Nîmes, France; Department of Pharmacology, AP-HP.Sorbonne Université, Pitié-Salpêtrière Hospital, 47, Bd de l'Hôpital, F-75013 Paris, France; Department of Pharmacology, Sorbonne Université Médecine, F-75013 Paris, France. Electronic address: gbensimon.psl@gmail.com.
Université de Montpellier · FRKing's College London · GBHumanitas University · ITSorbonne Université · FRUniversity of Sheffield · GBBrighton and Sussex Medical School · GBCentre Hospitalier Universitaire de Nîmes · FRGenethon (France) · FRQueen Mary University of London · GBUK Dementia Research Institute · GBUniversity of Gothenburg · SE

Funding

Motor Neurone Disease Association ALCHALABI-TALBOT/APR14/926-794
6 · The paper itself

Abstract

backgroundLow-dose interleukin-2 (ld-IL-2) enhances regulatory T-cell (Treg) function in auto-inflammatory conditions. Neuroinflammation being a pathogenic feature of amyotrophic lateral sclerosis (ALS), we evaluated the pharmacodynamics and safety of ld-IL-2 in ALS subjects.

methodsWe performed a single centre, parallel three-arm, randomised, double-blind, placebo-controlled study. Eligibility criteria included age < 75 years, disease duration < 5 years, riluzole treatment > 3 months, and a slow vital capacity ≥ 70% of normal. Patients were randomised (1:1:1) to aldesleukin 2 MIU, 1 MIU, or placebo once daily for 5 days every 4 weeks for 3 cycles. Primary outcome was change from baseline in Treg percentage of CD4

findingsAll randomised patients (12 per group), recruited from October 2015 to December 2015, were alive at the end of follow-up and included in the intent-to-treat (ITT) analysis. No drug-related serious adverse event was observed. Non-serious adverse events occurred more frequently with the 1 and 2 MIU IL-2 doses compared to placebo, including injection site reactions and flu-like symptoms. Primary outcome analysis showed a significant increase (p < 0·0001) in %Tregs in the 2 MIU and 1 MIU arms (mean [SD]: 2 MIU: +6·2% [2·2]; 1 MIU: +3·9% [1·2]) as compared to placebo (mean [SD]: -0·49% [1·3]). Effect sizes (ES) were large in treated groups: 2 MIU ES=3·7 (IC95%: 2·3-4·9) and 1 MIU ES=3·5 (IC95%: 2·1-4·6). Secondary outcomes showed a significant increase in %Tregs following repeated cycles (p < 0·0001) as compared to placebo, and a dose-dependent decrease in plasma CCL2 (p = 0·0049). There were no significant differences amongst the three groups on plasma NFL levels.

interpretationLd-IL-2 is well tolerated and immunologically effective in subjects with ALS. These results warrant further investigation into their eventual therapeutic impact on slowing ALS disease progression.

fundingThe French Health Ministry (PHRC-I-14-056), EU H2020 (grant #633413), and the Association pour la Recherche sur la SLA (ARSLA).

Indexed as

AgedAged, 80 and overAmyotrophic Lateral SclerosisAntineoplastic AgentsBiomarkersChemokinesCytokinesFemaleHumansImmunophenotypingInterleukin-2MaleMiddle AgedRecombinant ProteinsT-Lymphocytes, RegulatoryT-Lymphocyte SubsetsaldesleukinAntineoplastic AgentsBiomarkersChemokinesCytokinesInterleukin-2Recombinant ProteinsAmyotrophic lateral sclerosisBiomarkersLow dose interleukin-2Neuro-inflammationRandomised clinical trialRegulatory T cells

Identifiers

PMID32651161
PMCPMC7502670
OpenAlexW3039341768

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

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.