Impact of Immunosuppression Adjustment on COVID-19 Vaccination Response in Kidney Transplant Recipients (ADIVKT)

Impact of Immunosuppression Adjustment on the Immune Response to SARS-CoV-2 mRNA Vaccination in Kidney Transplant Recipients (ADIVKT)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19; Immunosuppression; Vaccine Response Impaired
• Intervention / Treatment: Drug: Reduction in antimetabolite immunosuppression

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California, Davis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Immunosuppression reduction; Reduction of immunosuppression before and after administration of a third dose of SARS-CoV-2 mRNA vaccine	Drug: Reduction in antimetabolite immunosuppression; Reduction in dose in mycophenolate mofetil/mycophenolic acid (MMF) or azathioprine before and after receiving 3rd dose vaccination
No Intervention: Standard of care; No change to immunosuppression before or after receipt of a third dose of SARS-Co-2 mRNA vaccine

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: University of California, Davis
• Collaborators: CareDx

Publications and helpful links

General Publications

• Khan SF. Vaccination in kidney disease: what did we learn from COVID-19 pandemic. Curr Opin Nephrol Hypertens. 2023 Sep 1;32(5):412-417. doi: 10.1097/MNH.0000000000000901. Epub 2023 May 23.

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2021
• Primary Completion (Estimated): December 24, 2026
• Study Completion (Estimated): December 24, 2026

Study Registration Dates

• First Submitted: September 24, 2021
• First Submitted That Met QC Criteria: September 27, 2021
• First Posted (Actual): September 29, 2021

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Molecular Mechanisms of Pharmacological Action; Antimetabolites
• Other Study ID Numbers: 1801321

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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.: Yes