search
Back to results

Use of cSVF Via IV Deployment for Residual Lung Damage After Symptomatic COVID-19 Infection (GARM-COVID19)

Primary Purpose

Pulmonary Alveolar Proteinosis, COPD, Idiopathic Pulmonary Fibrosis

Status
Enrolling by invitation
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Microcannula Harvest Adipose Derived tissue stromal vascular fraction (tSVF)
Centricyte 1000
IV Deployment Of cSVF In Sterile Normal Saline IV Solution
Liberase Enzyme (Roche)
Sterile Normal Saline for Intravenous Use
Sponsored by
Black Tie Medical, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Alveolar Proteinosis

Eligibility Criteria

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

Inclusion Criteria:

  • Must have confirmed and documented Coronaviral (COVID-19) infection history with involvement of lung tissues
  • Must be clear of any viral shed residual confirmed by negative viral testing protocol accepted by the Center for Disease Control (CDC) and/or the FDA
  • Must have discharge confirmation from infectious disease managing Provider declaring freedom of viral load or active infection
  • Must have a written Medical History of Physical and discharge summary (if hospitalized) from appropriate Center or Licensed Medical Provider
  • Must agree to provide a HRCT LUNG study done at baseline (before), 3 months and 6 months
  • Must be able to provide full Informed Consent (ICF)

Exclusion Criteria:

  • Active or positive testing of COVID-19 With Clinical Report and Discharge Summary from Hospital or Treatment Facility
  • Lung disorder without prior confirmation by approved test protocol of history of COVID-19
  • Patient health or condition deemed dangerous or inappropriate for transport, exceeding acceptable stress for transport or care needed to achieve access to the clinical facility, at the discretion of the Providers
  • Expected lifespan of < 6 months
  • Serious of life threatening co-morbidities, that in the opinion of the investigators, may compromise the safety or compliance with the study guidelines and tracking

Sites / Locations

  • Robert W. Alexander, MD, FICS, LLC

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Other

Other

Arm Label

Lipoaspiration

Isolation & Concentration of cSVF

Delivery cSVF via Intravenous

Liberase TM

Sterile Normal Saline

Arm Description

Closed sterile, disposable microcannula of small volume adipose tissue, including the stromal vascular fraction (SVF) (cells and stromal tissue

Isolation & Concentration of cellular stromal vascular fraction (cSVF) using Healeon Centricyte 1000 Centrifuge, incubator and shaker plate with sterile Liberase enzyme (Roche Medical) per manufacturer protocols

cSVF from Arm 2 is suspended in a 250 cc of sterile Normal Saline IV solution and deployed though 150 micron in-line filtration and intravenous route over 30-60 minute timeframe

Use of sterile Liberase TM enzyme to allow cSVF separation and isolation

250 cc of sterile Normal Saline for Intravenous with sterile 150 micron in-line filtration for suspension of the concentrated cSVF and deployment IV

Outcomes

Primary Outcome Measures

Incidence of Treatment-Emergent Adverse Events
Reporting of Adverse Events or Severe Adverse Events Assessed by CTCAE v4.0

Secondary Outcome Measures

Pulmonary Function Analysis
High Resolution Computerized Tomography of Lung (HRCT Lung) for Fluidda Analysis comparative at baseline and 3 and 6 months post-treatment comparative analytics
Digital Oximetry
Finger Pulse Oximetry taken before and after 6 minute walk on level ground, compare desaturation tendency

Full Information

First Posted
March 26, 2020
Last Updated
February 21, 2023
Sponsor
Black Tie Medical, Inc.
Collaborators
Robert W. Alexander, MD
search

1. Study Identification

Unique Protocol Identification Number
NCT04326036
Brief Title
Use of cSVF Via IV Deployment for Residual Lung Damage After Symptomatic COVID-19 Infection
Acronym
GARM-COVID19
Official Title
Use of cSVF For Residual Lung Damage (COPD/Fibrotic Lung Disease After Symptomatic COVID-19 Infection For Residual Pulmonary Injury or Post-Adult Respiratory Distress Syndrome Following Viral (SARS-Co-2) Infection
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
March 25, 2020 (Actual)
Primary Completion Date
August 1, 2023 (Anticipated)
Study Completion Date
January 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Black Tie Medical, Inc.
Collaborators
Robert W. Alexander, MD

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
COVID-19 Viral Global Pandemic resulting in post-infection pulmonary damage, including Fibrotic Lung Disease due to inflammatory and reactive protein secretions damaging pulmonary alveolar structure and functionality. A short review includes: Early December, 2019 - A pneumonia of unknown cause was detected in Wuhan, China, and was reported to the World Health Organization (WHO) Country Office. January 30th, 2020 - The outbreak was declared a Public Health Emergency of International Concern. February 7th, 2020 - 34-year-old Ophthalmologist who first identified a SARS-like coronavirus) dies from the same virus. February 11th, 2020 - WHO announces a name for the new coronavirus disease: COVID-19. February 19th, 2020 - The U.S. has its first outbreak in a Seattle nursing home which were complicated with loss of lives.. March 11th, 2020 - WHO declares the virus a pandemic and in less than three months, from the time when this virus was first detected, the virus has spread across the entire planet with cases identified in every country including Greenland. March 21st, 2020 - Emerging Infectious Disease estimates the risk for death in Wuhan reached values as high as 12% in the epicenter of the epidemic and ≈1% in other, more mildly affected areas. The elevated death risk estimates are probably associated with a breakdown of the healthcare system, indicating that enhanced public health interventions, including social distancing and movement restrictions, should be implemented to bring the COVID-19 epidemic under control." March 21st 2020 -Much of the United States is currently under some form of self- or mandatory quarantine as testing abilities ramp up.. March 24th, 2020 - Hot spots are evolving and identified, particularly in the areas of New York-New Jersey, Washington, and California. Immediate attention is turned to testing, diagnosis, epidemiological containment, clinical trials for drug testing started, and work on a long-term vaccine started. The recovering patients are presenting with mild to severe lung impairment as a result of the viral attack on the alveolar and lung tissues. Clinically significant impairment of pulmonary function appears to be a permanent finding as a direct result of the interstitial lung damage and inflammatory changes that accompanied. This Phase 0, first-in-kind for humans, is use of autologous, cellular stromal vascular fraction (cSVF) deployed intravenously to examine the anti-inflammatory and structural potential to improve the residual, permanent damaged alveolar tissues of the lungs.
Detailed Description
COVID-19 Viral Global Pandemic resulting in post-infection pulmonary damage, including Fibrotic Lung Disease due to inflammatory and reactive protein secretions damaging pulmonary alveolar structure and functionality. A short review includes: Early December, 2019 - A pneumonia of unknown cause was detected in Wuhan, China, and was reported to the World Health Organization (WHO) Country Office. January 30th, 2020 - The outbreak was declared a Public Health Emergency of International Concern. February 7th, 2020 - 34-year-old Ophthalmologist who first identified a SARS-like coronavirus) dies from the same virus. February 11th, 2020 - WHO announces a name for the new coronavirus disease: COVID-19. February 19th, 2020 - The U.S. has its first outbreak in a Seattle nursing home which were complicated with loss of lives.. March 11th, 2020 - WHO declares the virus a pandemic and in less than three months, from the time when this virus was first detected, the virus has spread across the entire planet with cases identified in every country including Greenland. March 11th, 2020 - As of this date, Over 60% of all COVID-19 deaths in the U.S. can be traced to that single nursing home in Seattle. March 11th, 2020 - Dr. Fauci from the National Institutes of Health (NIH) states, "If you count all the estimated cases of people who may have it but haven't been diagnosed yet, the mortality rate is probably closer to 1%," he said, "which means it's 10 times more lethal than the seasonal flu." March 21st, 2020 - The U.S. has 24,105 active cases, 301 deaths, and 171 patients declared recovered, a number which has since massively increased within the United States and Globally. March 21st, 2020 - Emerging Infectious Disease estimates the risk for death in Wuhan reached values as high as 12% in the epicenter of the epidemic and ≈1% in other, more mildly affected areas. The elevated death risk estimates are probably associated with a breakdown of the healthcare system, indicating that enhanced public health interventions, including social distancing and movement restrictions, should be implemented to bring the COVID-19 epidemic under control." March 21st 2020 -Much of the United States is currently under some form of self- or mandatory quarantine as testing abilities ramp up.. March 24th, 2020 - Hot spots are evolving and identified, particularly in the areas of New York-New Jersey, Washington, and California Immediate attention is turned to testing, diagnosis, epidemiological containment, clinical trials for drug testing started, and work on a long-term vaccine started. The recovering patients are presenting with mild to severe lung impairment as a result of the viral attack on the alveolar and lung tissues. Clinically significant impairment of pulmonary function appears to be a permanent finding as a direct result of the interstitial lung damage and inflammatory changes that accompanied. This Phase 0, first-in-kind for humans, is use of autologous, cSVF deployed intravenously to examine the anti-inflammatory and structural potential to improve the residual damaged tissues. Previous utilization of cSVF remains in Clinical Trials at this moment for uses in Chronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrotic Lung disorders, showing encouraging safety profile and clinical efficacy. It is the intention of this study, driven by the ongoing pandemic as a direct causative etiology for permanent lung damage within the oxygen/carbon dioxide exchange resulting the the direct alveolar disruption and scarring reaction. The inflammatory mediation, autoimmune modulatory capabilities, and revascularization potentials of the cSVF is becoming well recognized and documented in peer-reviewed literature and in scientific studies. Due to the urgency presented from the ongoing CoronaVirus pandemic, many patients that survive experience demonstrate direct pulmonary damage residua. There is available a relative new technology offered by Fluidda Inc in European Union (EU) known as "Functional Respiratory Imaging (FRI) and examines pulmonary function and vascular capabilities in damaged lung tissues. This study examines the lung baseline (post-infection), and at 3 and 6 month intervals post-cSVF treatment to examine the functional airway configuration and efficiency at those intervals. Sporadic reports of use of stem cells or stem/stromal cells have revealed some positive clinical outcomes, although not within a traditional randomized trial format at this point in time. This study proposed in the specific situation of permanent residual dysfunction created by the SARS-Co2 (Coronavirus) infection is felt to warrant a pilot study using the cSVF that is in current Clinical Trials, which, at this point presents a very good safety profile with the absence of adverse event (AE) or severe adverse events (SAE) as yet reported by the trials.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Alveolar Proteinosis, COPD, Idiopathic Pulmonary Fibrosis, Viral Pneumonia, Coronavirus Infection, Interstitial Lung Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Lipoaspiration
Arm Type
Experimental
Arm Description
Closed sterile, disposable microcannula of small volume adipose tissue, including the stromal vascular fraction (SVF) (cells and stromal tissue
Arm Title
Isolation & Concentration of cSVF
Arm Type
Experimental
Arm Description
Isolation & Concentration of cellular stromal vascular fraction (cSVF) using Healeon Centricyte 1000 Centrifuge, incubator and shaker plate with sterile Liberase enzyme (Roche Medical) per manufacturer protocols
Arm Title
Delivery cSVF via Intravenous
Arm Type
Experimental
Arm Description
cSVF from Arm 2 is suspended in a 250 cc of sterile Normal Saline IV solution and deployed though 150 micron in-line filtration and intravenous route over 30-60 minute timeframe
Arm Title
Liberase TM
Arm Type
Other
Arm Description
Use of sterile Liberase TM enzyme to allow cSVF separation and isolation
Arm Title
Sterile Normal Saline
Arm Type
Other
Arm Description
250 cc of sterile Normal Saline for Intravenous with sterile 150 micron in-line filtration for suspension of the concentrated cSVF and deployment IV
Intervention Type
Procedure
Intervention Name(s)
Microcannula Harvest Adipose Derived tissue stromal vascular fraction (tSVF)
Intervention Description
Use of Disposable Microcannula Closed System (Tulip Med, 2.2 mm) Harvest of Autologous Adipose Stroma and Stem/Stromal Cell Content
Intervention Type
Device
Intervention Name(s)
Centricyte 1000
Intervention Description
Centricyte 1000 (Healeon Medical) Digestive (sterile Roche Liberase TM) Isolation/Concentration Protocol, Rinsing/Neutralization, and Pelletize the cSVF For Deployment Via Sterile Saline IV fluid Standard Protocol
Intervention Type
Procedure
Intervention Name(s)
IV Deployment Of cSVF In Sterile Normal Saline IV Solution
Intervention Description
Sterile Normal Saline Suspension cSVF in 250cc for Intravenous Delivery Including Use of 150 micron in-line filtration
Intervention Type
Drug
Intervention Name(s)
Liberase Enzyme (Roche)
Other Intervention Name(s)
Proteolytic Emzyme
Intervention Description
Sterile Collagenase Blend to separate cSVF from the AD-SVF
Intervention Type
Drug
Intervention Name(s)
Sterile Normal Saline for Intravenous Use
Other Intervention Name(s)
Suspensory Fluid for cSVF
Intervention Description
Sterile Normal Saline IV solution to provide suspension of cSVF in 250 cc via standard IV line, including sterile 150 micron in-line standard filter
Primary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events
Description
Reporting of Adverse Events or Severe Adverse Events Assessed by CTCAE v4.0
Time Frame
1 month
Secondary Outcome Measure Information:
Title
Pulmonary Function Analysis
Description
High Resolution Computerized Tomography of Lung (HRCT Lung) for Fluidda Analysis comparative at baseline and 3 and 6 months post-treatment comparative analytics
Time Frame
baseline, 3 Month, 6 months
Title
Digital Oximetry
Description
Finger Pulse Oximetry taken before and after 6 minute walk on level ground, compare desaturation tendency
Time Frame
3 months, 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Must have confirmed and documented Coronaviral (COVID-19) infection history with involvement of lung tissues Must be clear of any viral shed residual confirmed by negative viral testing protocol accepted by the Center for Disease Control (CDC) and/or the FDA Must have discharge confirmation from infectious disease managing Provider declaring freedom of viral load or active infection Must have a written Medical History of Physical and discharge summary (if hospitalized) from appropriate Center or Licensed Medical Provider Must agree to provide a HRCT LUNG study done at baseline (before), 3 months and 6 months Must be able to provide full Informed Consent (ICF) Exclusion Criteria: Active or positive testing of COVID-19 With Clinical Report and Discharge Summary from Hospital or Treatment Facility Lung disorder without prior confirmation by approved test protocol of history of COVID-19 Patient health or condition deemed dangerous or inappropriate for transport, exceeding acceptable stress for transport or care needed to achieve access to the clinical facility, at the discretion of the Providers Expected lifespan of < 6 months Serious of life threatening co-morbidities, that in the opinion of the investigators, may compromise the safety or compliance with the study guidelines and tracking
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert W Alexander, MD
Organizational Affiliation
Global Alliance Regenerative Medicine
Official's Role
Study Chair
Facility Information:
Facility Name
Robert W. Alexander, MD, FICS, LLC
City
Stevensville
State/Province
Montana
ZIP/Postal Code
59870
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
In discussion phase
Citations:
Citation
Alexander, Robert W., Overview of Cellular Stromal Vascular Fraction (cSVF) & Biocellular Uses of Stem/Stromal Cells & Matrix (tSVF + HD-PRP) in Regenerative Medicine, Aesthetic Medicine and Plastic Surgery. 2019, S1003, DOI: 10.24966/SRDT-2060/S1003.
Results Reference
background
Citation
Alexander, Robert W., Understanding Adipose-Derived Stromal Vascular Fraction (AD-SVF) Cell Biology and Use on the Basis of Cellular, Chemical, Structural and Paracrine Components. (2012), J of Prolotherapy, 4: 855-869.
Results Reference
background
PubMed Identifier
32105632
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.
Results Reference
background
PubMed Identifier
32064853
Citation
Epidemiology Working Group for NCIP Epidemic Response, Chinese Center for Disease Control and Prevention. [The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China]. Zhonghua Liu Xing Bing Xue Za Zhi. 2020 Feb 10;41(2):145-151. doi: 10.3760/cma.j.issn.0254-6450.2020.02.003. Chinese.
Results Reference
background
PubMed Identifier
32127666
Citation
Li G, De Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov. 2020 Mar;19(3):149-150. doi: 10.1038/d41573-020-00016-0. No abstract available.
Results Reference
background
PubMed Identifier
22291007
Citation
Wu K, Peng G, Wilken M, Geraghty RJ, Li F. Mechanisms of host receptor adaptation by severe acute respiratory syndrome coronavirus. J Biol Chem. 2012 Mar 16;287(12):8904-11. doi: 10.1074/jbc.M111.325803. Epub 2012 Jan 30.
Results Reference
background
PubMed Identifier
32015507
Citation
Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Mar;579(7798):270-273. doi: 10.1038/s41586-020-2012-7. Epub 2020 Feb 3. Erratum In: Nature. 2020 Dec;588(7836):E6.
Results Reference
background
PubMed Identifier
15141376
Citation
Ding Y, He L, Zhang Q, Huang Z, Che X, Hou J, Wang H, Shen H, Qiu L, Li Z, Geng J, Cai J, Han H, Li X, Kang W, Weng D, Liang P, Jiang S. Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways. J Pathol. 2004 Jun;203(2):622-30. doi: 10.1002/path.1560.
Results Reference
background
PubMed Identifier
22496216
Citation
Kawase M, Shirato K, van der Hoek L, Taguchi F, Matsuyama S. Simultaneous treatment of human bronchial epithelial cells with serine and cysteine protease inhibitors prevents severe acute respiratory syndrome coronavirus entry. J Virol. 2012 Jun;86(12):6537-45. doi: 10.1128/JVI.00094-12. Epub 2012 Apr 11.
Results Reference
background
PubMed Identifier
25945397
Citation
Zhang R, Pan Y, Fanelli V, Wu S, Luo AA, Islam D, Han B, Mao P, Ghazarian M, Zeng W, Spieth PM, Wang D, Khang J, Mo H, Liu X, Uhlig S, Liu M, Laffey J, Slutsky AS, Li Y, Zhang H. Mechanical Stress and the Induction of Lung Fibrosis via the Midkine Signaling Pathway. Am J Respir Crit Care Med. 2015 Aug 1;192(3):315-23. doi: 10.1164/rccm.201412-2326OC.
Results Reference
background

Learn more about this trial

Use of cSVF Via IV Deployment for Residual Lung Damage After Symptomatic COVID-19 Infection

We'll reach out to this number within 24 hrs