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

NCT04326036 | Unknown Early Phase 1 DMC FDA Drug

• 1 other identifier: GARM COVID19
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Pulmonary Alveolar Proteinosis; COPD; Idiopathic Pulmonary Fibrosis; Viral Pneumonia; Coronavirus Infection; Interstitial Lung Disease

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  Reporting of Adverse Events or Severe Adverse Events Assessed by CTCAE v4.0

  1 month

Secondary Outcomes (2)

• Pulmonary Function Analysis

  baseline, 3 Month, 6 months

• Digital Oximetry

  3 months, 6 months

Study Arms (5)

Lipoaspiration

EXPERIMENTAL

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

Procedure: Microcannula Harvest Adipose Derived tissue stromal vascular fraction (tSVF)

Isolation & Concentration of cSVF

EXPERIMENTAL

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

Device: Centricyte 1000; Drug: Liberase Enzyme (Roche)

Delivery cSVF via Intravenous

EXPERIMENTAL

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

Procedure: IV Deployment Of cSVF In Sterile Normal Saline IV Solution; Drug: Sterile Normal Saline for Intravenous Use

Liberase TM

OTHER

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

Device: Centricyte 1000; Drug: Liberase Enzyme (Roche)

Sterile Normal Saline

OTHER

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

Procedure: IV Deployment Of cSVF In Sterile Normal Saline IV Solution; Drug: Sterile Normal Saline for Intravenous Use

Interventions

Microcannula Harvest Adipose Derived tissue stromal vascular fraction (tSVF) PROCEDURE

Use of Disposable Microcannula Closed System (Tulip Med, 2.2 mm) Harvest of Autologous Adipose Stroma and Stem/Stromal Cell Content

Lipoaspiration

Centricyte 1000 DEVICE

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

Isolation & Concentration of cSVF; Liberase TM

IV Deployment Of cSVF In Sterile Normal Saline IV Solution PROCEDURE

Sterile Normal Saline Suspension cSVF in 250cc for Intravenous Delivery Including Use of 150 micron in-line filtration

Delivery cSVF via Intravenous; Sterile Normal Saline

Liberase Enzyme (Roche) DRUG

Sterile Collagenase Blend to separate cSVF from the AD-SVF

Also known as: Proteolytic Emzyme

Isolation & Concentration of cSVF; Liberase TM

Sterile Normal Saline for Intravenous Use DRUG

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

Also known as: Suspensory Fluid for cSVF

Delivery cSVF via Intravenous; Sterile Normal Saline

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Black Tie Medical, Inc.: lead
• Robert W. Alexander, MD: collaborator

Study Sites (1)

Robert W. Alexander, MD, FICS, LLC

Stevensville, Montana, 59870, United States

Location

Related Publications (10)

• 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.

  BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 32105632 BACKGROUND

• 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.

  PMID: 32064853 BACKGROUND

• 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.

  PMID: 32127666 BACKGROUND

• 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.

  PMID: 22291007 BACKGROUND

• 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.

  PMID: 32015507 BACKGROUND

• 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.

  PMID: 15141376 BACKGROUND

• 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.

  PMID: 22496216 BACKGROUND

• 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.

  PMID: 25945397 BACKGROUND

MeSH Terms

Conditions

Pulmonary Alveolar Proteinosis; Pulmonary Disease, Chronic Obstructive; Idiopathic Pulmonary Fibrosis; Pneumonia, Viral; Coronavirus Infections; Lung Diseases, Interstitial

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pulmonary Fibrosis; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections

Study Officials

• Robert W Alexander, MD

  Global Alliance Regenerative Medicine

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2020
• First Posted: March 30, 2020
• Study Start: March 25, 2020
• Primary Completion: August 1, 2023
• Study Completion: January 31, 2024
• Last Updated: February 22, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)