Low-dose interleukin-2 in patients with stable ischaemic heart disease and acute coronary syndromes (LILACS): protocol and study rationale for a randomised, double-blind, placebo-controlled, phase I/II clinical trial.
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Authors
Kostapanos, Michalis
Griffiths, Charmaine
Arbon, Emma L
Hubsch, Annette
Kaloyirou, Fotini
Helmy, Joanna
Hoole, Stephen P
Rudd, James HF
Wood, Graham
Burling, Keith
Bond, Simon
Cheriyan, Joseph
Mallat, Ziad
Publication Date
2018-09-17Journal Title
BMJ Open
ISSN
2044-6055
Publisher
BMJ
Volume
8
Issue
9
Pages
e022452
Language
eng
Type
Article
Physical Medium
Electronic
Metadata
Show full item recordCitation
Zhao, T. X., Kostapanos, M., Griffiths, C., Arbon, E. L., Hubsch, A., Kaloyirou, F., Helmy, J., et al. (2018). Low-dose interleukin-2 in patients with stable ischaemic heart disease and acute coronary syndromes (LILACS): protocol and study rationale for a randomised, double-blind, placebo-controlled, phase I/II clinical trial.. BMJ Open, 8 (9), e022452. https://doi.org/10.1136/bmjopen-2018-022452
Abstract
INTRODUCTION: Inflammation and dysregulated immune responses play a crucial role in atherosclerosis, underlying ischaemic heart disease (IHD) and acute coronary syndromes (ACSs). Immune responses are also major determinants of the postischaemic injury in myocardial infarction. Regulatory T cells (CD4+CD25+FOXP3+; Treg) induce immune tolerance and preserve immune homeostasis. Recent in vivo studies suggested that low-dose interleukin-2 (IL-2) can increase Treg cell numbers. Aldesleukin is a human recombinant form of IL-2 that has been used therapeutically in several autoimmune diseases. However, its safety and efficacy is unknown in the setting of coronary artery disease. METHOD AND ANALYSIS: Low-dose interleukin-2 in patients with stable ischaemic heart disease and acute coronary syndromes is a single-centre, first-in-class, dose-escalation, two-part clinical trial. Patients with stable IHD (part A) and ACS (part B) will be randomised to receive either IL-2 (aldesleukin; dose range 0.3-3×106 IU) or placebo once daily, given subcutaneously, for five consecutive days. Part A will have five dose levels with five patients in each group. Group 1 will receive a dose of 0.3×106 IU, while the dose for the remaining four groups will be determined on completion of the preceding group. Part B will have four dose levels with eight patients in each group. The dose of the first group will be based on part A. Doses for each of the subsequent three groups will similarly be determined after completion of the previous group. The primary endpoint is safety and tolerability of aldesleukin and to determine the dose that increases mean circulating Treg levels by at least 75%. ETHICS AND DISSEMINATION: The study received a favourable opinion by the Greater Manchester Central Research Ethics Committee, UK (17/NW/0012). The results of this study will be reported through peer-reviewed journals, conference presentations and an internal organisational report. TRIAL REGISTRATION NUMBER: NCT03113773; Pre-results.
Keywords
Humans, Myocardial Ischemia, Natriuretic Peptide, Brain, C-Reactive Protein, Troponin, Recombinant Proteins, Interleukin-2, Interleukin-6, Immunologic Factors, Lymphocyte Count, Double-Blind Method, T-Lymphocytes, Regulatory, Randomized Controlled Trials as Topic, Clinical Trials, Phase I as Topic, Clinical Trials, Phase II as Topic, Acute Coronary Syndrome
Sponsorship
Medical Research Council (MR/N028015/1)
Engineering and Physical Sciences Research Council (EP/N014588/1)
British Heart Foundation (None)
British Heart Foundation (None)
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
British Heart Foundation (RG/15/11/31593)
Identifiers
External DOI: https://doi.org/10.1136/bmjopen-2018-022452
This record's URL: https://www.repository.cam.ac.uk/handle/1810/284745
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