Ignite Creation Date:
2024-05-06 @ 8:14 PM
Last Modification Date:
2024-10-26 @ 3:23 PM
Study NCT ID:
NCT06304623
Status:
COMPLETED
Last Update Posted:
2024-03-12
First Post:
2024-03-05
Brief Title:
SVF for Treating Pulmonary Fibrosis Post COVID-19
Sponsor:
Michael H Carstens
Organization:
Michael H Carstens
Study Overview
Official Title:
The Role of Cellular Therapy With SVF Cells Stromal Vascular Fraction of Adipose Tissue Origin in the Treatment of Pulmonary Fibrosis Post COVD-19
Status:
COMPLETED
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SVFCOVID-19
Brief Summary:
General description of the study
This is a prospective multicenter expanded access interventional study of subjects recovered from COVID-19 pneumonia to assess their response to intravenous administration of adipose-derived autologous SVF
Primary objective
The purpose of this study was to evaluate the safety of single intravenous injections of autologous adipose-derived SVF produced using the GID SVF-2 device system for the treatment of secondary respiratory distress associated with COVID-19
Secondary objective
To evaluate the efficacy of the initial treatment with SVF IV
This is a prospective multicenter expanded access interventional study of subjects recovered from COVID-19 pneumonia to assess their response to intravenous administration of adipose-derived autologous SVF
Primary objective
The purpose of this study was to evaluate the safety of single intravenous injections of autologous adipose-derived SVF produced using the GID SVF-2 device system for the treatment of secondary respiratory distress associated with COVID-19
Secondary objective
To evaluate the efficacy of the initial treatment with SVF IV
Detailed Description:
The recent outbreak of Coronavirus 2 SARS-CoV-2 has spread rapidly throughout the world resulting in a global pandemic with devastating socioeconomic consequences After being declared a public health emergency by the World Health Organization WHO there is an urgent need to develop effective therapeutic strategies for critically ill COVID-19 patients This new virus strain causes a complex disease with a wide range of presentations from mild symptoms to multi-organ failure A common feature of severe cases is the pathologically complex cytokine storm that presents as an excessive immune response with rapid progression of disease and high mortality In particular the severe outcomes of SARS CoV-2 are associated with elevated C-reactive protein and Interleukin-6 in the lungs COVID-19 infection can rapidly decompensate into severe respiratory failure requiring intubation and mechanical ventilation The need for mechanical ventilation portends a poor prognosis with a reported mortality rate of up to 88
Survivors of COVID-19 pneumonia face sequelae of their disease that affect multiple organ systems In particular a significant number present with ongoing problems of breathlessness and reduced oxygenation turning previously healthy patients into virus-induced pulmonary cripples The mechanism for this is the intense scarring and destruction of the microcirculation found in the lungs of COVID-19 survivors There is an urgent need for the development of treatment protocols that are capable of reducing the degree of pulmonary fibrosis and promoting local angiogenesis to better support injured alveoli
In recent decades mesenchymal stromal cells MSCs have emerged as a potential therapeutic agent for cell-based therapies due to the beneficial effects on immunomodulation and tissue repairregeneration These cells possess properties unique self-renewal and capacity to differentiate into multiple lineages MSCs are found in small numbers in bone marrow BMSC and umbilical cord tissue MSCs are also found in adipose tissue referred to as ASCs where they exist as part of a multicellular population the stromal vascular fraction SVF ASC populations are 500-1000 more abundant than their bone marrow counterparts
Adipose tissue provides a source of Stromal Vascular Fraction SVF that can be isolated and transplanted to the patient during the same surgical procedure at the point of care SVF is a heterogeneous mixture of stromal progenitor cells pericytes endothelial precursor cells and macrophages Acting collectively SVF has been shown to possess broad anti-inflammatory and regenerative properties SVF has been shown to be safe after IV administration and has shown some promising results in restoring respiratory function in patients with severe lung disorders Based on public analysis of single cell RNA sequencing scRNA-seq data SVF demonstrates the absence of ACE2 expression indicating its potential as a resistant phenotype to SARS-CoV-2 infection In Taken together IV administration of adipose- derived SVF is presented as a novel treatment approach to improve the clinical outcome of respiratory-compromised COVID-19 patients
The clinical impact of SVF for COVID-19 is based on 5 mechanisms of action These have been widely documented see attached publications and bibliography
Anti-inflammatory Immunomodulation especially T-regs Antifibrosis Matrix metalloproteinases and liver growth factor Support for regenerative cell populations in situ Lung asthma studies Angiogenesis under ischemic conditions based on the release of VEGF
Therapy with SVF cells from adipose tissue is advantageous as large numbers of cells can be removed from small volumes 30-90 cc by a minimally invasive liposuction procedure
Indication for expanded access
This is an expanded access study to treat a small group of subjects with pulmonary sequelae after recovery from COVID-19 pneumonia of autologous adipose-derived SVF administered using as single intravenous injection
Objectives of clinical research
Main objective
To assess the safety of a single injection of autologous adipose-derived SVF produced with the GID SVF-2 device for the treatment of respiratory distress
associated with COVID-19
Secondary objective
To assess efficacy by 1 maintaining SaO2 saturation at the existing level on noninvasive oxygen support 2 achieving a reduction in the level of oxygen support required to maintain SaO2 92 using intravenous injection of autologous adipose derived SVF produced using the GID SVF-2 device system for the treatment of respiratory distress associated with COVID-19
Expected duration of the clinical investigation
Follow-up controls at 3 6 9 and 12 months The total duration of the study is 1 year
Clinical Protocol
Study design
General study design
This is a prospective multicenter expanded access interventional study of subjects with COVID-19 Forty 40 subjects with confirmed COVID-19 and SaO2 92 were treated Subjects received an intravenous injection of autologous adipose-derived SVF Subjects will be followed for 6 weeks
Study procedures
Detection procedures
The initial evaluation was done at the local Centro de Salud Subjects were then referred to HEODRA or HECAM for confirmatory diagnosis and additional tests
Concomitant medications
All concomitant medications considered Standard of Care are accepted A concomitant medication case report form will be completed at each subject follow-up visit
Summary of study treatment
40 non-randomized patients will be treated with autologous SVF Minimum dosage 45x106 5x106 cells Treatment plan a single intervention
Follow-up Serum samples 20 cc - inflammation factors 1 month 3 months 6 months PFTs DLco preop 1 month 3 months 6 months weeks and 12 months CT preop 3 months 6 months 12 months SF-36 quality of life questionnaire SF-36 Medical Outcomes Trust pre-op 12 months SGRQ-C respiratory questionnaire SGRQ-C St Georges University pre-op 12 months
The subjects adipose tissue will be acquired by liposuction of the abdomen or flanks and placed directly into the GID SVF-2 device The harvested adipose tissue will be enzymatically digested in the same GID SVF-2 device using the GIDZyme-2-70 enzyme and centrifuged in the same GID SVF-2 device to concentrate the SVF cells SVF cells will be removed and an active treatment dose of 45 x 106 5 x 106 SVF cells will be injected into a 100 ml IV bag containing LR Fluids will be given through an IV catheter through a blood filter over 10 minutes
Dosage
Dose preparation
Using the LunaStem Nucleocounter Cell Concentration and Dilution Factor 100 calculate the volume needed using the following equation and transfer that amount of resuspension to a 10 mL syringe
ml dose 40 x 106 - 5x106
Dose administration The way to administer SVF for vascular use is the same whether it is intravenous IV or intravenous IA
The treatment was administered intravenously using an intravenous catheter with a blood filter
Add the dose to a 100 ml bag of LR that has been warmed to 37C and mix well Administer the 100 ml over 10 minutes
Adherence to treatment
Each subject had time to read the consent form and ask questions about the study before signing the informed consent Subjects should contact the physician or staff if participant have any concerns during the study It will be emphasized that the subject must comply with the protocol and be honest about her symptoms
Withdrawal of subjects for non-compliance
Subjects may be terminated from the study at the discretion of the principal investigator only for reasons related to study examinations that would jeopardize the subjects health andor welfare if participants were to continue in the study Subjects may voluntarily withdraw from the study at any time without prejudice
Subjects withdrawn will not be replaced if participant have received study treatment
Schedule of study visits
The initial evaluation and informed consent took place in the hospitals Prior to treatment subjects were evaluated to determine if participant meet the inclusionexclusion criteria If not already provided demographics medical history concomitant medications SaO2 and arterial blood gases was collected The subject were enrolled if participant meet all the eligibility criteria and have signed the Informed Consent
The time between enrollment and treatment not exceeded 48 hours
On the day of treatment each subject was reassessed for inclusion in the study
Survivors of COVID-19 pneumonia face sequelae of their disease that affect multiple organ systems In particular a significant number present with ongoing problems of breathlessness and reduced oxygenation turning previously healthy patients into virus-induced pulmonary cripples The mechanism for this is the intense scarring and destruction of the microcirculation found in the lungs of COVID-19 survivors There is an urgent need for the development of treatment protocols that are capable of reducing the degree of pulmonary fibrosis and promoting local angiogenesis to better support injured alveoli
In recent decades mesenchymal stromal cells MSCs have emerged as a potential therapeutic agent for cell-based therapies due to the beneficial effects on immunomodulation and tissue repairregeneration These cells possess properties unique self-renewal and capacity to differentiate into multiple lineages MSCs are found in small numbers in bone marrow BMSC and umbilical cord tissue MSCs are also found in adipose tissue referred to as ASCs where they exist as part of a multicellular population the stromal vascular fraction SVF ASC populations are 500-1000 more abundant than their bone marrow counterparts
Adipose tissue provides a source of Stromal Vascular Fraction SVF that can be isolated and transplanted to the patient during the same surgical procedure at the point of care SVF is a heterogeneous mixture of stromal progenitor cells pericytes endothelial precursor cells and macrophages Acting collectively SVF has been shown to possess broad anti-inflammatory and regenerative properties SVF has been shown to be safe after IV administration and has shown some promising results in restoring respiratory function in patients with severe lung disorders Based on public analysis of single cell RNA sequencing scRNA-seq data SVF demonstrates the absence of ACE2 expression indicating its potential as a resistant phenotype to SARS-CoV-2 infection In Taken together IV administration of adipose- derived SVF is presented as a novel treatment approach to improve the clinical outcome of respiratory-compromised COVID-19 patients
The clinical impact of SVF for COVID-19 is based on 5 mechanisms of action These have been widely documented see attached publications and bibliography
Anti-inflammatory Immunomodulation especially T-regs Antifibrosis Matrix metalloproteinases and liver growth factor Support for regenerative cell populations in situ Lung asthma studies Angiogenesis under ischemic conditions based on the release of VEGF
Therapy with SVF cells from adipose tissue is advantageous as large numbers of cells can be removed from small volumes 30-90 cc by a minimally invasive liposuction procedure
Indication for expanded access
This is an expanded access study to treat a small group of subjects with pulmonary sequelae after recovery from COVID-19 pneumonia of autologous adipose-derived SVF administered using as single intravenous injection
Objectives of clinical research
Main objective
To assess the safety of a single injection of autologous adipose-derived SVF produced with the GID SVF-2 device for the treatment of respiratory distress
associated with COVID-19
Secondary objective
To assess efficacy by 1 maintaining SaO2 saturation at the existing level on noninvasive oxygen support 2 achieving a reduction in the level of oxygen support required to maintain SaO2 92 using intravenous injection of autologous adipose derived SVF produced using the GID SVF-2 device system for the treatment of respiratory distress associated with COVID-19
Expected duration of the clinical investigation
Follow-up controls at 3 6 9 and 12 months The total duration of the study is 1 year
Clinical Protocol
Study design
General study design
This is a prospective multicenter expanded access interventional study of subjects with COVID-19 Forty 40 subjects with confirmed COVID-19 and SaO2 92 were treated Subjects received an intravenous injection of autologous adipose-derived SVF Subjects will be followed for 6 weeks
Study procedures
Detection procedures
The initial evaluation was done at the local Centro de Salud Subjects were then referred to HEODRA or HECAM for confirmatory diagnosis and additional tests
Concomitant medications
All concomitant medications considered Standard of Care are accepted A concomitant medication case report form will be completed at each subject follow-up visit
Summary of study treatment
40 non-randomized patients will be treated with autologous SVF Minimum dosage 45x106 5x106 cells Treatment plan a single intervention
Follow-up Serum samples 20 cc - inflammation factors 1 month 3 months 6 months PFTs DLco preop 1 month 3 months 6 months weeks and 12 months CT preop 3 months 6 months 12 months SF-36 quality of life questionnaire SF-36 Medical Outcomes Trust pre-op 12 months SGRQ-C respiratory questionnaire SGRQ-C St Georges University pre-op 12 months
The subjects adipose tissue will be acquired by liposuction of the abdomen or flanks and placed directly into the GID SVF-2 device The harvested adipose tissue will be enzymatically digested in the same GID SVF-2 device using the GIDZyme-2-70 enzyme and centrifuged in the same GID SVF-2 device to concentrate the SVF cells SVF cells will be removed and an active treatment dose of 45 x 106 5 x 106 SVF cells will be injected into a 100 ml IV bag containing LR Fluids will be given through an IV catheter through a blood filter over 10 minutes
Dosage
Dose preparation
Using the LunaStem Nucleocounter Cell Concentration and Dilution Factor 100 calculate the volume needed using the following equation and transfer that amount of resuspension to a 10 mL syringe
ml dose 40 x 106 - 5x106
Dose administration The way to administer SVF for vascular use is the same whether it is intravenous IV or intravenous IA
The treatment was administered intravenously using an intravenous catheter with a blood filter
Add the dose to a 100 ml bag of LR that has been warmed to 37C and mix well Administer the 100 ml over 10 minutes
Adherence to treatment
Each subject had time to read the consent form and ask questions about the study before signing the informed consent Subjects should contact the physician or staff if participant have any concerns during the study It will be emphasized that the subject must comply with the protocol and be honest about her symptoms
Withdrawal of subjects for non-compliance
Subjects may be terminated from the study at the discretion of the principal investigator only for reasons related to study examinations that would jeopardize the subjects health andor welfare if participants were to continue in the study Subjects may voluntarily withdraw from the study at any time without prejudice
Subjects withdrawn will not be replaced if participant have received study treatment
Schedule of study visits
The initial evaluation and informed consent took place in the hospitals Prior to treatment subjects were evaluated to determine if participant meet the inclusionexclusion criteria If not already provided demographics medical history concomitant medications SaO2 and arterial blood gases was collected The subject were enrolled if participant meet all the eligibility criteria and have signed the Informed Consent
The time between enrollment and treatment not exceeded 48 hours
On the day of treatment each subject was reassessed for inclusion in the study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None