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Repeated 5-day cycl...
Repeated 5-day cycles of low dose aldesleukin in amyotrophic lateral sclerosis (IMODALS): A phase 2a randomised, double-blind, placebo-controlled trial
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Camu, W. (författare)
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Mickunas, M. (författare)
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Veyrune, J. L. (författare)
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visa fler...
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Payan, C. (författare)
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Garlanda, C. (författare)
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Locati, M. (författare)
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Juntas-Morales, R. (författare)
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Pageot, N. (författare)
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Malaspina, A. (författare)
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- Andreasson, Ulf, 1968 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Kirby, J. (författare)
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Suehs, C. (författare)
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Saker, S. (författare)
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Masseguin, C. (författare)
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De Vos, J. (författare)
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- Zetterberg, Henrik, 1973 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Shaw, P. J. (författare)
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Al-Chalabi, A. (författare)
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Leigh, P. N. (författare)
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Tree, T. (författare)
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Bensimon, G. (författare)
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(creator_code:org_t)
- Elsevier BV, 2020
- 2020
- Engelska.
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 59
- Relaterad länk:
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http://www.thelancet...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: Low-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. Methods: We 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+ T cells (%Tregs) following a first cycle. Secondary laboratory outcomes included: %Treg and Treg number following repeated cycles, and plasma CCL2 and neurofilament light chain protein (NFL) concentrations as surrogate markers of efficacy. Safety outcomes included motor-function (ALSFRS-R), slow vital capacity (SVC), and adverse event reports. This trial is registered with ClinicalTrials.gov, NCT02059759. Findings: All 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. Interpretation: Ld-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. Funding: : The French Health Ministry (PHRC-I-14-056), EU H2020 (grant #633413), and the Association pour la Recherche sur la SLA (ARSLA). © 2020 The Authors
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Amyotrophic lateral sclerosis
- Biomarkers
- Low dose interleukin-2
- Neuro-inflammation
- Randomised clinical trial
- Regulatory T cells
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Camu, W.
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Mickunas, M.
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Veyrune, J. L.
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Payan, C.
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Garlanda, C.
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Locati, M.
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visa fler...
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Juntas-Morales, ...
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Pageot, N.
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Malaspina, A.
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Andreasson, Ulf, ...
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Kirby, J.
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Suehs, C.
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Saker, S.
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Masseguin, C.
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De Vos, J.
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Zetterberg, Henr ...
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Shaw, P. J.
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Al-Chalabi, A.
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Leigh, P. N.
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Tree, T.
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Bensimon, G.
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Neurovetenskaper
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EBioMedicine
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Göteborgs universitet