Herpes Virus Infections in Kidney Transplant Patients (HINT)

April 9, 2024 updated by: Susanne Dam Nielsen, MD, DMSc

Investigation of Kidney Transplant Patients for Antibodies and T-cells After Herpes Virus Vaccination and Infection

Kidney transplant recipients are at increased risk of infections, including Varicella-zoster virus (VZV) infections. Vaccination against VZV is routinely offered to all kidney transplant recipients and candidates in Denmark. In this exploratory observational study, the VZV specific immune response in kidney transplant candidates and recipients will be characterized at different time points in relation to transplantation, vaccination and infections. More knowledge on the immune reaction to transplantation, VZV vaccination and VZV infections may provide improved strategies for prevention and treatment of VZV infections in kidney transplant candidates and recipients.

Study Overview

Status

Recruiting

Conditions

Detailed Description

Kidney transplantation is a life-saving procedure for patients with kidney failure, and in 2021, 252 kidney transplantations were performed in Denmark. Varicella-zoster virus (VZV) is a vaccine-preventable disease that causes varicella during primary infection and herpes zoster when reactivated later in life. VZV is one of the most common infections after organ transplantation, and kidney transplant recipients have high risk of herpes zoster (annual incidence: 3 per 100). Furthermore, kidney transplant recipients that acquire herpes zoster have high risk of disseminated and severe disease as well as increased risk of post-herpetic neuralgia.

Until 2021, the only available VZV/herpes zoster vaccines in Europe were live vaccines, and live vaccines are contraindicated in immunosuppressed individuals due to the risk of infection with the vaccine strain. However, a new, non-live, recombinant subunit herpes zoster vaccine (Shingrix®) that can be used in immunosuppressed individuals was recently approved and became available in Denmark in October 2021.

The efficacy of Shingrix® in healthy individuals is excellent (90%) both with regard to preventing herpes zoster and post-herpetic neuralgia. However, organ transplant recipients receive high doses of immunosuppressive medication, and information on efficacy and immunogenicity of Shingrix® in immunosuppressed individuals is sparse. One randomized study found the efficacy of the vaccine to be good (68%) in patients after hematopoietic stem cell transplantation. Furthermore, one phase III randomized, placebo-controlled study was conducted in 246 kidney transplant recipients, and the vaccine was found to be safe and to induce antibody responses, but the study was not powered to demonstrate efficacy.

At present, international guidelines recommend vaccination against herpes zoster prior to or after transplantation, but there is no information about the optimal timing of vaccination or duration of the immune response in transplant recipients.

Poor or no antibody response after vaccinations are documented among organ transplant recipients. Vaccination prior to transplantation or early post-transplantation may be of benefit because patients are at the highest risk of infections early post-transplantation due to high load of immunosuppressive therapy, however, this is also the period with the highest risk of non-response to vaccines. It is therefore of great importance, for both individual patients and for society, to determine the optimal timing of vaccination, response rates and duration of protection prior to use of vaccines in organ transplant recipients.

The investigators will conduct a prospective observational exploratory study including kidney transplant candidates and recipients who are offered Shingrix® vaccination. Shingrix® vaccination is routine care, and vaccination is not a part of the study, and acceptance of vaccination is not mandatory to participate in the study. The study is a national collaboration that includes all Danish kidney transplantation centers and kidney transplant recipients from all Danish regions. The study has potential to contribute with necessary information to design optimal programs for vaccine roll-out and thereby to reduce the incidence of herpes zoster and herpes zoster-related complications including hospital admissions in kidney transplant recipients as well as other solid organ transplant recipients. Furthermore, the investigators will explore differences in the immune systems of kidney transplant recipients who get VZV infections and those who don't.

The study aims to include 875 patients, of which 500 will be kidney transplant recipients (250 who are 6-12 months post-transplantation, 125 who are 12-18 months post-transplantation and 125 who are >24 months post-transplantation) and 375 kidney transplant candidates from the kidney transplant waitlist.

For participants on the transplant waitlist, blood will be collected at inclusion and 1, 2, 6 and 12 months post-inclusion, as well as 6 and 12 months post-transplantation and in the case of VZV infection. For participants who are already transplanted at inclusion, blood will be collected at inclusion, and 1, 2, 6 and 12 months post-inclusion and in the case of VZV infection. Plasma and peripheral blood mononuclear cells (PBMC) will be stored in a biobank.

All participants will be asked at inclusion to fill out a questionnaire regarding health, lifestyle, and vaccine history. At follow-ups, participants will be asked to fill out a questionnaire regarding changes in VZV infection history, vaccination history, transplant related factors and medication. Furthermore, health data will be collected from hospital records and national registries. Measurement of VZV glycoprotein E antibodies will be done using enzyme-linked immunosorbent assays (ELISA). Identification and phenotyping of VZV-specific T cells will be done through DNA-barcode labelling and flow cytometry. Cytokine profiling will be done using a Luminex MILLIPLEX assay. Analyses will be performed at the Technical University of Denmark.

Study Type

Observational

Enrollment (Estimated)

875

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Denmark
      • Aarhus, Denmark
        • Recruiting
        • Department of Nephrology, Aarhus University Hospital
        • Contact:
      • Copenhagen, Denmark, 2100
        • Recruiting
        • Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet
        • Contact:
          • Susanne D Nielsen, Professor, MD, DMSc
      • Copenhagen, Denmark, 2100
      • Lyngby, Denmark, 2800
        • Recruiting
        • Department of Health Technology, Technical University of Denmark
        • Contact:
          • Sine R Hadrup, Professor, MSc, PhD
        • Contact:
      • Odense, Denmark
        • Recruiting
        • Department of Nephrology, Odense University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Kidney transplant recipients transplanted after 2019-01-01 and kidney transplant candidates followed at Copenhagen University Hospital - Rigshospitalet, Aarhus University Hospital and Odense University Hospital who has been offered Shingrix® vaccination will be invited to participate

Description

Inclusion Criteria:

  • Kidney transplant recipient transplanted after 2019-01-01 OR on the kidney transplant waitlist
  • Has been offered Shingrix® vaccination

Exclusion Criteria:

  • Lack of informed consent
  • Inability to understand the study information

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Kidney transplant patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in levels of antibodies against Varicella-Zoster virus
Time Frame: 12 months
Measurement of the change in levels of antibodies against Varicella-Zoster virus glycoprotein E using enzyme-linked immunosorbent assays (ELISA). The change will be assessed at regular intervals up to 12 months after inclusion or transplantation as well as well as in the case of infection.
12 months
Change in presence and function of Varicella-Zoster virus-specific T cells
Time Frame: 12 months
Identification, phenotyping and cytokine profiling of Varicella-Zoster virus-specific T cells using DNA-barcode marking, flow cytometry and plasma cytokine profiles at regular intervals up to 12 months after inclusion or transplantation as well as in the case of infection.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Susanne Dam Nielsen, MD, DMSc

Collaborators

Odense University Hospital
Aarhus University Hospital
Technical University of Denmark

Investigators

  • Principal Investigator: Susanne D Nielsen, MD, DMSc, Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet
  • Study Chair: Søren S Sørensen, MD, DMSc, Department of Nephrology, Copenhagen University Hospital - Rigshospitalet
  • Study Chair: Claus Bistrup, MD, PhD, Department of Nephrology, Odense University Hospital
  • Study Chair: Henrik Birn, MD, PhD, DMSc, Department of Nephrology, Aarhus University Hospital
  • Study Chair: Sine R Hadrup, MSc, PhD, Department of Health Technology, Technical University of Denmark
  • Study Director: Annemette Hald, RN, Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet
  • Study Director: Sunil K Saini, MSc, PhD, Department of Health Technology, Technical University of Denmark
  • Study Director: Isik S Johansen, MD, DMSc, Department of Infectious Diseases, Odense University Hospital
  • Study Director: Helle Bruunsgaard, MD, PhD, DMSc, Department of Clinical Immunology, Copenhagen University Hospital - Rigshospitalet
  • Study Director: Carsten S Larsen, MD, DMSc, Department of Infectious Diseases, Aarhus University Hospital
  • Study Director: Zitta B Harboe, MD, PhD, Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital - North Zealand
  • Study Director: Moisés A Suarez Zdunek, MD, Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet
  • Study Director: Sebastian R Hamm, BSc.med., Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2023

Primary Completion (Estimated)

February 1, 2025

Study Completion (Estimated)

February 1, 2027

Study Registration Dates

First Submitted

September 19, 2022

First Submitted That Met QC Criteria

October 31, 2022

First Posted (Actual)

November 3, 2022

Study Record Updates

Last Update Posted (Actual)

April 10, 2024

Last Update Submitted That Met QC Criteria

April 9, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-22042603
  • 0073947 (Other Grant/Funding Number: Novo Nordisk Foundation)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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