Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05191381
Other study ID # Lung fibrosis in COVID19
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date December 22, 2021
Est. completion date December 31, 2026

Study information

Verified date January 2024
Source University of Ulm
Contact Manfred Weiss, MD
Phone +49(0)731500
Email manfred.weiss@uniklinik-ulm.de
Is FDA regulated No
Health authority
Study type Observational [Patient Registry]

Clinical Trial Summary

Following whole blood stimulation with mesenchymal stem cell derived exosomes, immune phenotype, cytokine release and mRNA expression patterns from critically ill patients with COVID-19 will be determined.


Description:

Critically ill patients with COVID-19 may develop lung failure and require extracorporal oxygenation due to hyperinflammation and progressive lung fibrosis. The anti-inflammatory and immune modulatory function of mesenchymal stem cells will be investigated by whole blood stimulation experiments using stem cell derived exosomes. Exosome preparations have been characterized by miRNA and protein expression patterns and suggest their tissue regenerative capacity. The hypothesis of the present study is that mesenchymal stem cell derived exosomes attenuate inflammation and support anti-fibrotic pathways.


Recruitment information / eligibility

Status Recruiting
Enrollment 40
Est. completion date December 31, 2026
Est. primary completion date July 31, 2025
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 90 Years
Eligibility Inclusion Criteria: - Critically ill COVID-19 patients with lung dysfunction - COVID-19 WHO severity degree >= 4, ARDS (WHO Definition 13 March 2020) - Body weight > 50 kg - Informed consent Exclusion Criteria: - Pregnant or breast feeding women

Study Design


Intervention

Biological:
Application of exosomes in a whole blood assay
Co-incubation of patient-derived whole blood samples with mesenchymal stem cell derived exosomes and read-out of biomarkers, RNA and immune phenotypes after 24h.

Locations

Country Name City State
Germany Ulm University Hospital, Clinic of Anesthesiology and Intensive Care Medicine Ulm

Sponsors (1)

Lead Sponsor Collaborator
University of Ulm

Country where clinical trial is conducted

Germany, 

References & Publications (17)

Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017 Jul;39(5):529-539. doi: 10.1007/s00281-017-0629-x. Epub 2017 May 2. — View Citation

Di Rocco G, Baldari S, Toietta G. Towards Therapeutic Delivery of Extracellular Vesicles: Strategies for In Vivo Tracking and Biodistribution Analysis. Stem Cells Int. 2016;2016:5029619. doi: 10.1155/2016/5029619. Epub 2016 Nov 23. — View Citation

Geistlinger J, Du W, Groll J, Liu F, Hoegel J, Foehr KJ, Pasquarelli A, Schneider EM. P2RX7 genotype association in severe sepsis identified by a novel Multi-Individual Array for rapid screening and replication of risk SNPs. Clin Chim Acta. 2012 Jan 18;413(1-2):39-47. doi: 10.1016/j.cca.2011.05.023. Epub 2011 May 25. — View Citation

Giamarellos-Bourboulis EJ, Netea MG, Rovina N, Akinosoglou K, Antoniadou A, Antonakos N, Damoraki G, Gkavogianni T, Adami ME, Katsaounou P, Ntaganou M, Kyriakopoulou M, Dimopoulos G, Koutsodimitropoulos I, Velissaris D, Koufargyris P, Karageorgos A, Katrini K, Lekakis V, Lupse M, Kotsaki A, Renieris G, Theodoulou D, Panou V, Koukaki E, Koulouris N, Gogos C, Koutsoukou A. Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure. Cell Host Microbe. 2020 Jun 10;27(6):992-1000.e3. doi: 10.1016/j.chom.2020.04.009. Epub 2020 Apr 21. — View Citation

Gotts JE, Matthay MA. Endogenous and exogenous cell-based pathways for recovery from acute respiratory distress syndrome. Clin Chest Med. 2014 Dec;35(4):797-809. doi: 10.1016/j.ccm.2014.08.015. Epub 2014 Sep 24. — View Citation

Haberle H, Magunia H, Lang P, Gloeckner H, Korner A, Koeppen M, Backchoul T, Malek N, Handgretinger R, Rosenberger P, Mirakaj V. Mesenchymal Stem Cell Therapy for Severe COVID-19 ARDS. J Intensive Care Med. 2021 Jun;36(6):681-688. doi: 10.1177/0885066621997365. Epub 2021 Mar 5. — View Citation

J. Bindja, M. E. Weiss, M. Schmolz, G. M. Stein, J. Mapes, N. Schneiderhan-Marra, T. O. Joos, E. M. Schneider. Synthetic ligands against TLR2-9 in TruCultureā„¢ - whole blood assays distinguish clinical stages of SIRS (trauma) and sepsis.Trauma, Shock, Inflammation and Sepsis.Trauma, Shock, Inflammation and Sepsis - TSIS 2010; 55 - 63

Lai RC, Arslan F, Lee MM, Sze NS, Choo A, Chen TS, Salto-Tellez M, Timmers L, Lee CN, El Oakley RM, Pasterkamp G, de Kleijn DP, Lim SK. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res. 2010 May;4(3):214-22. doi: 10.1016/j.scr.2009.12.003. Epub 2010 Jan 4. — View Citation

Leng Z, Zhu R, Hou W, Feng Y, Yang Y, Han Q, Shan G, Meng F, Du D, Wang S, Fan J, Wang W, Deng L, Shi H, Li H, Hu Z, Zhang F, Gao J, Liu H, Li X, Zhao Y, Yin K, He X, Gao Z, Wang Y, Yang B, Jin R, Stambler I, Lim LW, Su H, Moskalev A, Cano A, Chakrabarti S, Min KJ, Ellison-Hughes G, Caruso C, Jin K, Zhao RC. Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia. Aging Dis. 2020 Mar 9;11(2):216-228. doi: 10.14336/AD.2020.0228. eCollection 2020 Apr. — View Citation

Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0. Epub 2020 Mar 16. No abstract available. — View Citation

Monsel A, Zhu YG, Gudapati V, Lim H, Lee JW. Mesenchymal stem cell derived secretome and extracellular vesicles for acute lung injury and other inflammatory lung diseases. Expert Opin Biol Ther. 2016 Jul;16(7):859-71. doi: 10.1517/14712598.2016.1170804. Epub 2016 Apr 12. — View Citation

Sanders J., Schneider E.M. How severe RNA virus infections such as SARS-CoV-2 disrupt tissue and organ barriers-Reconstitution by mesenchymal stem cell-derived exosomes. Tissue Barriers in Disease, Injury and Regeneration 2021:95-113. doi: 10.1016/B978-0-

Shah TG, Predescu D, Predescu S. Mesenchymal stem cells-derived extracellular vesicles in acute respiratory distress syndrome: a review of current literature and potential future treatment options. Clin Transl Med. 2019 Sep 12;8(1):25. doi: 10.1186/s40169-019-0242-9. — View Citation

Shi L, Huang H, Lu X, Yan X, Jiang X, Xu R, Wang S, Zhang C, Yuan X, Xu Z, Huang L, Fu JL, Li Y, Zhang Y, Yao WQ, Liu T, Song J, Sun L, Yang F, Zhang X, Zhang B, Shi M, Meng F, Song Y, Yu Y, Wen J, Li Q, Mao Q, Maeurer M, Zumla A, Yao C, Xie WF, Wang FS. Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients: a randomized, double-blind, placebo-controlled phase 2 trial. Signal Transduct Target Ther. 2021 Feb 10;6(1):58. doi: 10.1038/s41392-021-00488-5. — View Citation

Shi L, Wang L, Xu R, Zhang C, Xie Y, Liu K, Li T, Hu W, Zhen C, Wang FS. Mesenchymal stem cell therapy for severe COVID-19. Signal Transduct Target Ther. 2021 Sep 8;6(1):339. doi: 10.1038/s41392-021-00754-6. — View Citation

Shi Y, Wang Y, Shao C, Huang J, Gan J, Huang X, Bucci E, Piacentini M, Ippolito G, Melino G. COVID-19 infection: the perspectives on immune responses. Cell Death Differ. 2020 May;27(5):1451-1454. doi: 10.1038/s41418-020-0530-3. Epub 2020 Mar 23. No abstract available. — View Citation

Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 May;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5. Epub 2020 Feb 24. Erratum In: Lancet Respir Med. 2020 Apr;8(4):e26. — View Citation

* Note: There are 17 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Cytokine profile in supernatants Quantification of pro- and anti-inflammatory biomarkers after 24 hours of whole blood culture 24 hours, 1 year
Secondary Immune phenotyping Immune phenotypes related to type I interferon signaling 1 year
Secondary Genetic predisposition to hyperinflammation Determination of functional single nucleotide polymorphisms of inflammatory genes and receptors 1 year
See also
  Status Clinical Trial Phase
Withdrawn NCT06065033 - Exercise Interventions in Post-acute Sequelae of Covid-19 N/A
Completed NCT06267534 - Mindfulness-based Mobile Applications Program N/A
Completed NCT05047601 - A Study of a Potential Oral Treatment to Prevent COVID-19 in Adults Who Are Exposed to Household Member(s) With a Confirmed Symptomatic COVID-19 Infection Phase 2/Phase 3
Recruiting NCT05323760 - Functional Capacity in Patients Post Mild COVID-19 N/A
Recruiting NCT04481633 - Efficacy of Pre-exposure Treatment With Hydroxy-Chloroquine on the Risk and Severity of COVID-19 Infection N/A
Completed NCT04612972 - Efficacy, Safety and Immunogenicity of Inactivated SARS-CoV-2 Vaccines (Vero Cell) to Prevent COVID-19 in Healthy Adult Population In Peru Healthy Adult Population In Peru Phase 3
Completed NCT04537949 - A Trial Investigating the Safety and Effects of One BNT162 Vaccine Against COVID-19 in Healthy Adults Phase 1/Phase 2
Recruiting NCT05494424 - Cognitive Rehabilitation in Post-COVID-19 Condition N/A
Active, not recruiting NCT06039449 - A Study to Investigate the Prevention of COVID-19 withVYD222 in Adults With Immune Compromise and in Participants Aged 12 Years or Older Who Are at Risk of Exposure to SARS-CoV-2 Phase 3
Enrolling by invitation NCT05589376 - You and Me Healthy
Completed NCT05158816 - Extracorporal Membrane Oxygenation for Critically Ill Patients With COVID-19
Recruiting NCT04341506 - Non-contact ECG Sensor System for COVID19
Completed NCT04512079 - FREEDOM COVID-19 Anticoagulation Strategy Phase 4
Completed NCT04384445 - Zofin (Organicell Flow) for Patients With COVID-19 Phase 1/Phase 2
Completed NCT05975060 - A Study to Evaluate the Safety and Immunogenicity of an (Omicron Subvariant) COVID-19 Vaccine Booster Dose in Previously Vaccinated Participants and Unvaccinated Participants. Phase 2/Phase 3
Active, not recruiting NCT05542862 - Booster Study of SpikoGen COVID-19 Vaccine Phase 3
Withdrawn NCT05621967 - Phonation Therapy to Improve Symptoms and Lung Physiology in Patients Referred for Pulmonary Rehabilitation N/A
Terminated NCT05487040 - A Study to Measure the Amount of Study Medicine in Blood in Adult Participants With COVID-19 and Severe Kidney Disease Phase 1
Terminated NCT04498273 - COVID-19 Positive Outpatient Thrombosis Prevention in Adults Aged 40-80 Phase 3
Active, not recruiting NCT06033560 - The Effect of Non-invasive Respiratory Support on Outcome and Its Risks in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2)-Related Hypoxemic Respiratory Failure