Literature DB >> 33407796

Safety and clinical efficacy of the secretome of stressed peripheral blood mononuclear cells in patients with diabetic foot ulcer-study protocol of the randomized, placebo-controlled, double-blind, multicenter, international phase II clinical trial MARSYAS II.

Alfred Gugerell1,2, Ghazaleh Gouya-Lechner2, Helmut Hofbauer1,2, Maria Laggner1,2, Franz Trautinger3, Gabriele Almer4, Anja Peterbauer-Scherb5, Marcus Seibold2,5, Wolfram Hoetzenecker6, Christiane Dreschl7, Michael Mildner8, Hendrik Jan Ankersmit9,10.   

Abstract

BACKGROUND: Diabetes and its sequelae such as diabetic foot ulcer are rising health hazards not only in western countries but all over the world. Effective, yet safe treatments are desperately sought for by physicians, healthcare providers, and of course patients. METHODS/
DESIGN: APOSEC, a novel, innovative drug, is tested in the phase I/II study MARSYAS II, where its efficacy to promote healing of diabetic foot ulcers will be determined. To this end, the cell-free secretome of peripheral blood mononuclear cells (APOSEC) blended with a hydrogel will be applied topically three times weekly for 4 weeks. APOSEC is predominantly effective in hypoxia-induced tissue damages by modulating the immune system and enhancing angiogenesis, whereby its anti-microbial ability and neuro-regenerative capacity will exert further positive effects. In total, 132 patients will be enrolled in the multicenter, randomized, double-blind, placebo-controlled, parallel group, dose-ranging phase I/II study and treated with APOSEC at three dose levels or placebo for 4 weeks, followed by an 8-week follow-up period to evaluate safety and efficacy of the drug. Wound area reduction after 4 weeks of treatment will serve as the primary endpoint.
CONCLUSION: We consider our study protocol to be suitable to test topically administered APOSEC in patients suffering from diabetic foot ulcers in a clinical phase I/II trial. TRIAL REGISTRATION: EudraCT 2018-001653-27 . Registered on 30 July 2019. ClinicalTrials.gov NCT04277598 . Registered on 20 February 2020. TITLE: "A randomized, placebo-controlled, double-blind study to evaluate safety and dose-dependent clinical efficacy of APO-2 at three different doses in patients with diabetic foot ulcer (MARSYAS II)".

Entities:  

Keywords:  (Impaired) wound healing; Biological; Clinical trial protocol; Diabetic foot ulcer; Hydrogel; Inflammation; Peripheral blood mononuclear cells; Randomized controlled trial; Secretome-based therapy; Skin

Mesh:

Year:  2021        PMID: 33407796      PMCID: PMC7789696          DOI: 10.1186/s13063-020-04948-1

Source DB:  PubMed          Journal:  Trials        ISSN: 1745-6215            Impact factor:   2.279


  34 in total

1.  Practical guidelines on the management and prevention of the diabetic foot 2011.

Authors:  K Bakker; J Apelqvist; N C Schaper
Journal:  Diabetes Metab Res Rev       Date:  2012-02       Impact factor: 4.876

2.  Outcomes in controlled and comparative studies on non-healing wounds: recommendations to improve the quality of evidence in wound management.

Authors:  F Gottrup; J Apelqvist; P Price
Journal:  J Wound Care       Date:  2010-06       Impact factor: 2.072

3.  Stem cells conditioned medium: a new approach to skin wound healing management.

Authors:  Pukana Jayaraman; Prakash Nathan; Punitha Vasanthan; Sabri Musa; Vijayendran Govindasamy
Journal:  Cell Biol Int       Date:  2013-06-24       Impact factor: 3.612

4.  Diabetic foot syndrome.

Authors:  S Morbach; E Müller; H Reike; A Risse; G Rümenapf; M Spraul
Journal:  Exp Clin Endocrinol Diabetes       Date:  2014-07-11       Impact factor: 2.949

5.  Bone marrow cells are a rich source of growth factors and cytokines: implications for cell therapy trials after myocardial infarction.

Authors:  Mortimer Korf-Klingebiel; Tibor Kempf; Thomas Sauer; Eva Brinkmann; Philipp Fischer; Gerd P Meyer; Arnold Ganser; Helmut Drexler; Kai C Wollert
Journal:  Eur Heart J       Date:  2008-10-25       Impact factor: 29.983

6.  Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies.

Authors:  N Sarwar; P Gao; S R Kondapally Seshasai; R Gobin; S Kaptoge; E Di Angelantonio; E Ingelsson; D A Lawlor; E Selvin; M Stampfer; C D A Stehouwer; S Lewington; L Pennells; A Thompson; N Sattar; I R White; K K Ray; J Danesh
Journal:  Lancet       Date:  2010-06-26       Impact factor: 202.731

7.  Treatment of non-healing skin ulcers with autologous activated mononuclear cells.

Authors:  C Holzinger; A Zuckermann; C Kopp; A Schöllhammer; M Imhof; W Zwölfer; I Baumgartner; H Magometschnigg; E Weissinger; E Wolner
Journal:  Eur J Vasc Surg       Date:  1994-05

8.  Safety and tolerability of topically administered autologous, apoptotic PBMC secretome (APOSEC) in dermal wounds: a randomized Phase 1 trial (MARSYAS I).

Authors:  Elisabeth Simader; Denise Traxler; Mohammad Mahdi Kasiri; Helmut Hofbauer; Michael Wolzt; Christoph Glogner; Angela Storka; Michael Mildner; Ghazaleh Gouya; Alexandra Geusau; Carola Fuchs; Claudia Eder; Alexandra Graf; Michaela Schaden; Bahar Golabi; Marie-Bernadette Aretin; Susanne Suessner; Christian Gabriel; Walter Klepetko; Erwin Tschachler; Hendrik Jan Ankersmit
Journal:  Sci Rep       Date:  2017-07-24       Impact factor: 4.379

9.  Toxicological testing of allogeneic secretome derived from peripheral mononuclear cells (APOSEC): a novel cell-free therapeutic agent in skin disease.

Authors:  Silvio Wuschko; Alfred Gugerell; Monika Chabicovsky; Helmut Hofbauer; Maria Laggner; Michael Erb; Tobias Ostler; Anja Peterbauer; Susanne Suessner; Svitlana Demyanets; Jost Leuschner; Bernhard Moser; Michael Mildner; Hendrik J Ankersmit
Journal:  Sci Rep       Date:  2019-04-03       Impact factor: 4.379

10.  Analysis of the Secretome of Apoptotic Peripheral Blood Mononuclear Cells: Impact of Released Proteins and Exosomes for Tissue Regeneration.

Authors:  Lucian Beer; Matthias Zimmermann; Andreas Mitterbauer; Adolf Ellinger; Florian Gruber; Marie-Sophie Narzt; Maria Zellner; Mariann Gyöngyösi; Sibylle Madlener; Elisabeth Simader; Christian Gabriel; Michael Mildner; Hendrik Jan Ankersmit
Journal:  Sci Rep       Date:  2015-11-16       Impact factor: 4.379

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  4 in total

Review 1.  Future Directions in Research in Transcriptomics in the Healing of Diabetic Foot Ulcers.

Authors:  Brandon J Sumpio; Zhuqing Li; Enya Wang; Ikram Mezghani; Georgios Theocharidis; Aristidis Veves
Journal:  Adv Ther       Date:  2022-10-20       Impact factor: 4.070

2.  Paracrine Factors of Stressed Peripheral Blood Mononuclear Cells Activate Proangiogenic and Anti-Proteolytic Processes in Whole Blood Cells and Protect the Endothelial Barrier.

Authors:  Dragan Copic; Martin Direder; Klaudia Schossleitner; Maria Laggner; Katharina Klas; Daniel Bormann; Hendrik Jan Ankersmit; Michael Mildner
Journal:  Pharmaceutics       Date:  2022-07-30       Impact factor: 6.525

3.  Secretome of Stressed Peripheral Blood Mononuclear Cells Alters Transcriptome Signature in Heart, Liver, and Spleen after an Experimental Acute Myocardial Infarction: An In Silico Analysis.

Authors:  Caterina Selina Mildner; Dragan Copic; Matthias Zimmermann; Michael Lichtenauer; Martin Direder; Katharina Klas; Daniel Bormann; Alfred Gugerell; Bernhard Moser; Konrad Hoetzenecker; Lucian Beer; Mariann Gyöngyösi; Hendrik Jan Ankersmit; Maria Laggner
Journal:  Biology (Basel)       Date:  2022-01-13

Review 4.  Polymeric Hydrogels as Mesenchymal Stem Cell Secretome Delivery System in Biomedical Applications.

Authors:  Mia Arifka; Gofarana Wilar; Khaled M Elamin; Nasrul Wathoni
Journal:  Polymers (Basel)       Date:  2022-03-17       Impact factor: 4.329

  4 in total

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