COVID-19IMECOV19NCT05191381
Immune Modulation by Exosomes in COVID-19
An observational study of COVID-19 and Critical Illness, run by University of Ulm at 1 site in Germany.
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. Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- COVID-19, Critical Illness, Hypercytokinemia
- What is being tested?
- Application of exosomes in a whole blood assay
- How many people
- 40 participants
- Where
- 1 siteGermany
- Study dates
- 22 Dec 2021to 31 Dec 2026
- How long will I take part?
- 12 Months
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Critically ill COVID-19 patients, COVID-19 WHO severity degree >= 4, ARDS (WHO Definition 13 March 2020)
Who may be able to join
- 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
Who cannot join
- Pregnant or breast feeding women
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Germany1 site, 1 recruiting
- Recruiting
Ulm University Hospital, Clinic of Anesthesiology and Intensive Care Medicine
Ulm, 89070
Manfred Weiss, MD, MBA, +49-(0)731-500-60226, manfred.weiss@uniklinik-ulm.de
Marion Schneider, PhD, +49-(0)731-500-60080, marion.schneider@uni-ulm.de
About this study
Official title: Immune Modulation by Stem Cell Derived Exosomes in Critically Ill COVID-19
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.
Read the detailed 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.
- Conditions
- COVID-19, Critical Illness, Hypercytokinemia, Lung Fibrosis
- Being tested
- Application of exosomes in a whole blood assay
- Keywords
- COVID-19, Critical illness, Hypercytokinemia, Exosomes, Mesenchymal stem cells, Tissue reconstitution, Immune modulation, Sepsis
- Medical subject headings
- COVID-19, Critical Illness, Cytokine Release Syndrome, Pulmonary Fibrosis, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Application of exosomes in a whole blood assayBiological
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.
What is being measured
The primary outcome is the main question the study is designed to answer.
Cytokine profile in supernatants
Quantification of pro- and anti-inflammatory biomarkers after 24 hours of whole blood culture
Measured: 24 hours, 1 year
Secondary outcomes (2)
Immune phenotyping
Immune phenotypes related to type I interferon signaling
Measured: 1 year
Genetic predisposition to hyperinflammation
Determination of functional single nucleotide polymorphisms of inflammatory genes and receptors
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2022
- Study start22 Dec 2021
- Primary completion31 Jul 2025 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
- Target duration
- 12 Months
Sponsor and investigators
- Lead sponsor
- University of Ulm
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Manfred Weiss, University of Ulm
- Investigators
- Manfred Weiss, MD, Principal investigator, Clinic of Anaesthesiology and Intensive Care MedicineMarion Schneider, PhD, Principal investigator, Clinic of Anaesthesiology and Intensive Care Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05191381
- Sponsor's protocol ID
- Lung fibrosis in COVID19
- Acronym
- IMECOV19
- Status last verified
- Jan 2024
- First submitted
- 12 Jan 2022
- Last updated
- 17 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 28466096Di 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.
PubMed 27994623Geistlinger 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.
PubMed 21640086Giamarellos-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.
PubMed 32320677Gotts 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.
PubMed 25453426Haberle 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.
PubMed 33663244Lai 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.
PubMed 20138817Leng 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.
PubMed 32257537Mehta 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.
PubMed 32192578Monsel 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.
PubMed 27011289Shah 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.
PubMed 31512000Shi 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.
PubMed 32205856Shi 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.
PubMed 33568628Shi 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.
PubMed 34497264Yang 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.
PubMed 32105632
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immune Modulation by Stem Cell Derived Exosomes in Critically Ill COVID-19
- ClinicalTrials.gov ID
- NCT05191381
- Acronym / sponsor ID
- IMECOV19 / Lung fibrosis in COVID19
- Conditions
- COVID-19, Critical Illness, Hypercytokinemia, Lung Fibrosis
- Keywords
- COVID-19, Critical illness, Hypercytokinemia, Exosomes, Mesenchymal stem cells, Tissue reconstitution, Immune modulation, Sepsis
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of UlmUniversity, hospital or other
- Study start
- 22 Dec 2021 (actual)
- Primary completion
- 31 Jul 2025 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 13 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 12 Months
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Critically ill COVID-19 patients, COVID-19 WHO severity degree >= 4, ARDS (WHO Definition 13 March 2020)
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (1 listed)
- Pregnant or breast feeding women
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Application of exosomes in a whole blood assayCo-incubation of patient-derived whole blood samples with mesenchymal stem cell derived exosomes and read-out of biomarkers, RNA and immune phenotypes after 24h. | Biological | – |
Primary outcome
Cytokine profile in supernatants
Time frame: 24 hours, 1 year
Quantification of pro- and anti-inflammatory biomarkers after 24 hours of whole blood culture
2 secondary outcomes
Immune phenotyping
Time frame: 1 year
Genetic predisposition to hyperinflammation
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2024.
- Background: PubMed 28466096Channappanavar 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.
- Background: PubMed 27994623Di 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.
- Background: PubMed 21640086Geistlinger 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.
- Background: PubMed 32320677Giamarellos-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.
- Background: PubMed 25453426Gotts 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.
- Background: PubMed 33663244Haberle 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.
- Background: PubMed 20138817Lai 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.
- Background: PubMed 32257537Leng 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.
- Background: PubMed 32192578Mehta 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.
- Background: PubMed 27011289Monsel 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.
- Background: PubMed 31512000Shah 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.
- Background: PubMed 32205856Shi 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Manfred Weiss, MD principal investigator
Clinic of Anaesthesiology and Intensive Care Medicine
Marion Schneider, PhD principal investigator
Clinic of Anaesthesiology and Intensive Care Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COVID-19 and Critical Illness, run by University of Ulm at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Manfred Weiss, MD (+49(0)731500 ext. 60226, manfred.weiss@uniklinik-ulm.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cytokine profile in supernatants (time frame: 24 hours, 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05191381, which also lists 17 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jan 2024.