COVID-19, Immunosuppression, Vaccine Response Impaired
Conditions
Brief summary
Immunocompromised individuals, such as solid organ transplant (SOT) recipients are at high risk of COVID-19 associated complications and mortality. Retrospective studies so far have shown that a majority of SOT recipients did not develop appreciable anti-spike antibody response after a first, second, or even third dose of mRNA vaccine. Treatment with antimetabolites was associated with poor vaccine response. The goal of this study is 1) examine whether transient immunosuppression reduction improves the immune response to a third dose of SARS-CoV-2 mRNA vaccine in kidney transplant recipients and 2) to assess the safety of immunosuppression reduction before and after third dose SARS-CoV-2 mRNA vaccination.
Detailed description
This is a prospective, randomized open-labeled study of kidney transplant recipients who have previously received two doses of mRNA COVID-19 vaccine (either BNT162b2, Pfizer-BioNTech or mRNA-1273, Moderna) and who are eligible to receive a 3rd dose of mRNA vaccine.
Interventions
DRUGReduction in antimetabolite immunosuppression
Reduction in dose in mycophenolate mofetil/mycophenolic acid (MMF) or azathioprine before and after receiving 3rd dose vaccination
Sponsors
University of California, Davis
CareDx
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Prospective randomized open-labeled
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant is willing and able to give informed consent for participation in the study * First or repeat kidney transplant recipient * Negative or low positive antibody titer on SARS-CoV-2 antibody assay * On a mycophenolate or azathioprine based immunosuppressive regimen * \> 6 months post-transplant
Exclusion criteria
* Pregnancy * Contraindication to SARS-CoV-2 vaccination (severe allergic reactions or anaphylaxis)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in anti-SARS-CoV-2 IgG titer to SARS-CoV-2 target proteins from baseline | 6 weeks after receipt of 3rd dose mRNA vaccine |
| Percentage of participants who achieve high-positive antibody titer | 6 weeks after receipt of 3rd dose mRNA vaccine |
Secondary
| Measure | Time frame |
|---|---|
| Acute rejection | 1 week to 16 weeks after intervention |
| De Novo donor specific antibody (DSA) development | 4 week to 16 weeks after intervention |
| Change in donor-derived cell free DNA from baseline | 1 week to 16 weeks after intervention |
| Change in glomerular filtration rate (GFR) from baseline | 1 week to 16 weeks after intervention |
| Change in proteinuria from baseline | 1 week to 16 weeks after intervention |
Countries
United States
Outcome results
None listed