Ignite Creation Date:
2024-05-06 @ 4:31 PM
Last Modification Date:
2024-10-26 @ 2:12 PM
Study NCT ID:
NCT05019456
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2021-10-01
First Post:
2021-08-18
Brief Title:
Exercise and COVID-19 Viral T-cell Immunity
Sponsor:
University of Arizona
Organization:
University of Arizona
Study Overview
Official Title:
The Effect of Acute Exercise on the Mobilization of SARS-CoV-2 Specific T-cells
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
RECRUITING
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:
VIC
Brief Summary:
Viruses are a major health problem for the general public and at risk populations Normally detection of antibody titers is the gold standard for determining the effectiveness of the immune system following natural or vaccine caused immunization However determining the effectiveness of other parts of the immune system are less common due to the difficulties with testing Furthermore there is a critical need to address other therapies in case vaccination is not successful in immuncompromised populations Exercise has been shown to increase the strength of the immune system against many types of viruses and therefore could be simple way to improve immunity against the COVID-19 virus The aim of this research is to determine the effects of exercise on anti-viral immunity against many types of common viruses before and after vaccination We hypothesize that exercise will enhance the anti-viral immunity before and after vaccination
Up to 30 healthy volunteers age 18-44 years will be recruited to participate in this study For completion of Aim 1 three visits are needed totaling around 7 hours of the patients time and for Aim 2 three visits are needed totaling around 45 hours of the patients time The initial visit will be for pre-screening and if deemed healthy enough to participate an exercise test to determine the VO2 max of the participant will be conducted The following visits will require a trained phlebotomist to insert an in-dwelling catheter and participants will undergo a 20-minute incremental exercise trial Approximately 50mL of blood will be collected at four different timepoints at rest 60 VO2 max 80 VO2 max and 1-hr post-exercise All four collected blood samples will be used to expand viral specific T-cells and compare IFN-γ rele
Up to 30 healthy volunteers age 18-44 years will be recruited to participate in this study For completion of Aim 1 three visits are needed totaling around 7 hours of the patients time and for Aim 2 three visits are needed totaling around 45 hours of the patients time The initial visit will be for pre-screening and if deemed healthy enough to participate an exercise test to determine the VO2 max of the participant will be conducted The following visits will require a trained phlebotomist to insert an in-dwelling catheter and participants will undergo a 20-minute incremental exercise trial Approximately 50mL of blood will be collected at four different timepoints at rest 60 VO2 max 80 VO2 max and 1-hr post-exercise All four collected blood samples will be used to expand viral specific T-cells and compare IFN-γ rele
Detailed Description:
Acute upper and lower respiratory tract infections RTI due to respiratory viruses such as respiratory syncytial virus RSV influenza parainfluenza virus PIV and human metapneumovirus hMPV are a major public health problem During the 2019-2020 influenza season the Center for Disease Control CDC determined that influenza accounted for 38 million illnesses 18 million medical visits 405000 hospitalizations and 2200 deaths and annual costs of approximately 871 billion in disease management in the United States Simultaneously the COVID 19 pandemic is currently a major health crisis across of the United States and worldwide with the number of cases surpassing 50 million and deaths totaling more than 13 million Latent herpesviruses cytomegalovirus CMV Epstein Barr virus EBV and Varicella Zoster virus VZV are other types of viral infections that are easily controlled in healthy people but in immunocompromised people such as elderly or cancer patients these latent viruses can become deadly People receiving allogenic hematopoietic cell transplantation allo-HCT are at high risk of CMV infection and can lead to significant morbidity in transplant patients Due to these populations An acute bout of exercise as well as chronic exercise training have been shown to enhance anti-viral immunity against many of these respiratory viruses and latent herpesviruses However the immune response to viral infections is usually limited to the detection of humoral responses and the ability to produce antibodies titers is the gold standard for determining the effectiveness of the immune system in response to vaccination However monitoring the cellular immune response following natural or vaccine induced immunization less standardized Numerous laboratory techniques have been developed to test the cellular immune response including phenotyping antigen specific T-cells intracellular staining of cytokines ELISPOT or ELISA for antigen derived cytokine production and antigen specific cytotoxicity assays However theses assays are laborious and typically require highly specialized lab equipment and techniques Interferon-gamma IFN-γ release assays have been developed to focus on cellular immunity and could complement or replace these other laborious procedures Thus we propose that a single bout of exercise in humans will enhance the total antiviral immunity to numerous respiratory viruses and latent herpesviruses using a whole blood IFN-γ assay
Secondly there is a critical need to develop new therapeutics that can be used both prophylactically and in the treatment of SARS CoV-2 infections Adoptive cell therapy with viral specific T-cells VST has been used effectively to treat viral infections in immunocompromised patients particularly in recipients of hematopoietic stem cell transplantation This procedure has been used for 25 years with evidence of safety and efficacy No group to our knowledge has attempted to manufacture SARS CoV-2 VSTs as a potential therapeutic to prevent andor treat refractory SARS Co-V-2 infections during the current COVID-19 pandemic Having a personalized or third-party T-cell product that is banked and readily available could offer a life-saving intervention for many at-risk individuals eg the elderly cancer patients diabetics transplant recipients should they develop COVID-19 Current COVID-19 vaccination strategies are focused on inducing neutralizing antibodies This strain-specific approach is limited because immunity against drifted strains that emerge from one season to the next or even during a single season is often lost Given that T-cells offer protection against multiple viral strains there is strong rationale to develop a vaccine that targets T-cells capable of providing coronavirus heterotypic immunity Dendritic Cell DC vaccines pulsed with viral antigen peptides have been used successfully to elicit immune responses against influenza hepatitis C and HIV and could therefore serve as a personalized vaccine solution to the COVID-19 pandemic In the present study we plan to demonstrate preclinical proof of concept for a DC based vaccine by attempting to immunize humanized mice in vivo Our proposed NOD-scid-IL2Rγnull NSG mouse model has been used successfully to generate preclinical data for human DC and VST based vaccines
Secondly there is a critical need to develop new therapeutics that can be used both prophylactically and in the treatment of SARS CoV-2 infections Adoptive cell therapy with viral specific T-cells VST has been used effectively to treat viral infections in immunocompromised patients particularly in recipients of hematopoietic stem cell transplantation This procedure has been used for 25 years with evidence of safety and efficacy No group to our knowledge has attempted to manufacture SARS CoV-2 VSTs as a potential therapeutic to prevent andor treat refractory SARS Co-V-2 infections during the current COVID-19 pandemic Having a personalized or third-party T-cell product that is banked and readily available could offer a life-saving intervention for many at-risk individuals eg the elderly cancer patients diabetics transplant recipients should they develop COVID-19 Current COVID-19 vaccination strategies are focused on inducing neutralizing antibodies This strain-specific approach is limited because immunity against drifted strains that emerge from one season to the next or even during a single season is often lost Given that T-cells offer protection against multiple viral strains there is strong rationale to develop a vaccine that targets T-cells capable of providing coronavirus heterotypic immunity Dendritic Cell DC vaccines pulsed with viral antigen peptides have been used successfully to elicit immune responses against influenza hepatitis C and HIV and could therefore serve as a personalized vaccine solution to the COVID-19 pandemic In the present study we plan to demonstrate preclinical proof of concept for a DC based vaccine by attempting to immunize humanized mice in vivo Our proposed NOD-scid-IL2Rγnull NSG mouse model has been used successfully to generate preclinical data for human DC and VST based vaccines
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?:
None
Is an FDA AA801 Violation?:
None