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Adipose Mesenchymal Cells for Abatement of SARS-CoV-2 Respiratory Compromise in COVID-19 Disease

Primary Purpose

Covid-19 Pneumonia, Cyotokine Storm

Status

Not yet recruiting

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

Autologous Adipose MSC's

About this trial

This is an interventional treatment trial for Covid-19 Pneumonia focused on measuring Coronavirus, SARS-CoV-2, ARDS, Pandemic

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female patients ≥ 18 years of and less than 90
COVID 19 diagnosis confirmed
Ability to give informed consent
Hospitalized

Exclusion Criteria:

Mild Illness
1. Patients with uncomplicated upper respiratory tract viral infection, may have non-specific symptoms such as fever, fatigue, cough (with or without sputum production), anorexia, malaise, muscle pain, sore throat, dyspnea, nasal congestion, or headache. Rarely, patients may also present with diarrhea, nausea and vomiting.
2. The elderly and immunosuppressed candidates may present with atypical symptoms. Symptoms due to physiologic adaptations of pregnancy or adverse pregnancy events, such as e.g. dyspnea, fever, GI-symptoms or fatigue, may overlap with COVID-19 symptoms. Still, they will be excluded, unless they progress to Inclusion Criteria within 72 hours from recruitment.
Pneumonia (uncomplicated):
a. Adults with pneumonia but no signs of severe pneumonia AND NO need for supplemental oxygen
Reported pregnant or positive pregnancy test
Other chronic respiratory disorders such as COPD, emphysema, lung cancer, or cystic fibrosis
BMI lower than 21
Skinfold test < 3 cm at harvest area
Patients with Do-Not-Resuscitate orders that limit mechanical ventilation assistance in place at hospital admission
Males and females < 18 years of age
Patients who are currently breastfeeding
Co-Infection of HIV, tuberculosis, influenza virus, adenovirus and other respiratory infection viruses.
History of systemic malignant neoplasms within the last 5 years.
Subject is in the opinion of the Investigator or designee, unable to comply with the requirements of the study protocol or is unsuitable for the study for any reason
Participating in another clinical research study
History of Bleeding disorder which in PI's opinion would render the patient unsuitable for the study
PT (plasma) < 9 or >11.6 seconds and in the opinion of the PI and attending physician that lipoaspiration would be contraindicated. May be eligible for re-screening if coagulopathy improves within 72 hours of consent
PTT < 23 or >32 seconds and in the opinion of the PI and attending physician that lipoaspiration would be contraindicated. May be eligible for re-screening if coagulopathy improves within 72 hours of consent
Platelets count less than 70,0000
History of DVT

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Autologous Adipose Derived Mesenchymal Cells

Untreated

Arm Description

Conventional treatment plus MSC's IV

Conventional treatment only

Outcomes

Primary Outcome Measures

Safety - Incidence of unexpected adverse events

Incidence of unexpected adverse events within 28 days following IV administration of MSCs.

Efficacy - Frequency of progression to mechanical ventilation

Changes in progression or rate of subjects progressing to mechanical ventilation

Efficacy - Changes in length of mechanical ventilation

Changes in time subjects remain on mechanical ventilation

Efficacy - Changes in length of weaning of mechanical ventilation

Changes in length of time subjects wean off of mechanical ventilation

Efficacy - Changes in length of hospital stay

Length of Hospital Stay

Efficacy - Changes in mortality rate

Mortality rate from all causes

Secondary Outcome Measures

Full Information

NCT ID

NCT04352803

First Posted

April 16, 2020

Last Updated

April 17, 2020

Sponsor

Regeneris Medical

1. Study Identification

Unique Protocol Identification Number

NCT04352803

Brief Title

Adipose Mesenchymal Cells for Abatement of SARS-CoV-2 Respiratory Compromise in COVID-19 Disease

Official Title

IV Infusion of Autologous Adipose Derived Mesenchymal Cells for Abatement of Respiratory Compromise in SARS-CoV-2 Pandemic (COVID-19)

Study Type

Interventional

2. Study Status

Record Verification Date

April 2020

Overall Recruitment Status

Not yet recruiting

Study Start Date

April 2020 (Anticipated)

Primary Completion Date

April 2024 (Anticipated)

Study Completion Date

April 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Regeneris Medical

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The aim of this study is to evaluate the safety and efficacy of autologous adipose-derived mesenchymal cells for treating confirmed or suspected patients with SARS-CoV-2 and compromised respiratory function requiring hospitalization. The hypothesis of the Study is autologous adipose-derived mesenchymal cells given IV to eligible patients will improve clinical outcomes of COVID 19 positive patients with severe pneumonia or ARDS by reducing or avoiding cytokine storm.

Detailed Description

While most patients with SARS-CoV-2 present with mild respiratory disease with the most common symptoms of fever and cough, approximately 14 % progress to severe pneumonia and ARDS. The overall mortality rate is 2% but varies by country and age of the patient. In COVID-19 ARDS standard supportive care and treatment for underlying illnesses remain the mainstay with limited success. Numerous antiviral medications including remdesivir, lopinavir-ritonavir or lopinavir-ritonavir and interferon Beta-1a are in clinical trials but safety and efficacy remain unclear. Inflammation associated with a cytokine storm begins at a local site and spreads throughout the body via systemic circulation. The lungs and other organs are damaged with progressive inflammation. Mesenchymal cells offer the potential to treat viral infection both directly and through reducing the immune response. MSCs play a role as an immunomodulator, which is safe and effective as demonstrated in numerous clinical trials. Mesenchymal cells are a potential privileged cell-based therapy in SARS-CoV-2. MSCs derived extracellular vesicles have demonstrated comparable and sometimes more effective effects in ameliorating lung inflammation and injury.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Covid-19 Pneumonia, Cyotokine Storm

Keywords

Coronavirus, SARS-CoV-2, ARDS, Pandemic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Model Description

This is an Interventional, Prospective, Open label (Voluntary Assignment), single to multiple center expansion, unmatched controlled, Sequentially Interim analysis tested Trial

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Autologous Adipose Derived Mesenchymal Cells

Arm Type

Experimental

Arm Description

Conventional treatment plus MSC's IV

Arm Title

Untreated

Arm Type

No Intervention

Arm Description

Conventional treatment only

Intervention Type

Biological

Intervention Name(s)

Autologous Adipose MSC's

Intervention Description

Autologous Adipose Derived Mesenchymal Cells 500,000/kg IV

Primary Outcome Measure Information:

Title

Safety - Incidence of unexpected adverse events

Description

Incidence of unexpected adverse events within 28 days following IV administration of MSCs.

Time Frame

up to 28 days

Title

Efficacy - Frequency of progression to mechanical ventilation

Description

Changes in progression or rate of subjects progressing to mechanical ventilation

Time Frame

up to 28 days

Title

Efficacy - Changes in length of mechanical ventilation

Description

Changes in time subjects remain on mechanical ventilation

Time Frame

up to 28 days

Title

Efficacy - Changes in length of weaning of mechanical ventilation

Description

Changes in length of time subjects wean off of mechanical ventilation

Time Frame

up to 28 days

Title

Efficacy - Changes in length of hospital stay

Description

Length of Hospital Stay

Time Frame

up to 28 days

Title

Efficacy - Changes in mortality rate

Description

Mortality rate from all causes

Time Frame

up to 28 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female patients ≥ 18 years of and less than 90 COVID 19 diagnosis confirmed Ability to give informed consent Hospitalized Exclusion Criteria: Mild Illness Patients with uncomplicated upper respiratory tract viral infection, may have non-specific symptoms such as fever, fatigue, cough (with or without sputum production), anorexia, malaise, muscle pain, sore throat, dyspnea, nasal congestion, or headache. Rarely, patients may also present with diarrhea, nausea and vomiting. The elderly and immunosuppressed candidates may present with atypical symptoms. Symptoms due to physiologic adaptations of pregnancy or adverse pregnancy events, such as e.g. dyspnea, fever, GI-symptoms or fatigue, may overlap with COVID-19 symptoms. Still, they will be excluded, unless they progress to Inclusion Criteria within 72 hours from recruitment. Pneumonia (uncomplicated): a. Adults with pneumonia but no signs of severe pneumonia AND NO need for supplemental oxygen Reported pregnant or positive pregnancy test Other chronic respiratory disorders such as COPD, emphysema, lung cancer, or cystic fibrosis BMI lower than 21 Skinfold test < 3 cm at harvest area Patients with Do-Not-Resuscitate orders that limit mechanical ventilation assistance in place at hospital admission Males and females < 18 years of age Patients who are currently breastfeeding Co-Infection of HIV, tuberculosis, influenza virus, adenovirus and other respiratory infection viruses. History of systemic malignant neoplasms within the last 5 years. Subject is in the opinion of the Investigator or designee, unable to comply with the requirements of the study protocol or is unsuitable for the study for any reason Participating in another clinical research study History of Bleeding disorder which in PI's opinion would render the patient unsuitable for the study PT (plasma) < 9 or >11.6 seconds and in the opinion of the PI and attending physician that lipoaspiration would be contraindicated. May be eligible for re-screening if coagulopathy improves within 72 hours of consent PTT < 23 or >32 seconds and in the opinion of the PI and attending physician that lipoaspiration would be contraindicated. May be eligible for re-screening if coagulopathy improves within 72 hours of consent Platelets count less than 70,0000 History of DVT

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ryan Welter, MD PhD

Phone

(508) 576-8325

r.welter@regenerismedical.com

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

32109013

Citation

Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28.

Results Reference

background

PubMed Identifier

22797452

Citation

ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669.

Results Reference

background

PubMed Identifier

31986261

Citation

Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, Xing F, Liu J, Yip CC, Poon RW, Tsoi HW, Lo SK, Chan KH, Poon VK, Chan WM, Ip JD, Cai JP, Cheng VC, Chen H, Hui CK, Yuen KY. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020 Feb 15;395(10223):514-523. doi: 10.1016/S0140-6736(20)30154-9. Epub 2020 Jan 24.

Results Reference

background

PubMed Identifier

32081636

Citation

Lai CC, Shih TP, Ko WC, Tang HJ, Hsueh PR. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges. Int J Antimicrob Agents. 2020 Mar;55(3):105924. doi: 10.1016/j.ijantimicag.2020.105924. Epub 2020 Feb 17.

Results Reference

background

PubMed Identifier

32031570

Citation

Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585. Erratum In: JAMA. 2021 Mar 16;325(11):1113.

Results Reference

background

PubMed Identifier

32192578

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.

Results Reference

background

PubMed Identifier

32257537

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.

Results Reference

background

PubMed Identifier

24704622

Citation

Mohammadzadeh A, Pourfathollah AA, Shahrokhi S, Hashemi SM, Moradi SL, Soleimani M. Immunomodulatory effects of adipose-derived mesenchymal stem cells on the gene expression of major transcription factors of T cell subsets. Int Immunopharmacol. 2014 Jun;20(2):316-21. doi: 10.1016/j.intimp.2014.03.003. Epub 2014 Apr 3.

Results Reference

background

PubMed Identifier

11304456

Citation

Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001 Apr;7(2):211-28. doi: 10.1089/107632701300062859.

Results Reference

background

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Adipose Mesenchymal Cells for Abatement of SARS-CoV-2 Respiratory Compromise in COVID-19 Disease

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