Herpes Virus Infections in Kidney Transplant Patients

NCT ID: NCT05604911

Last Updated: 2025-04-06

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 280 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2026-02-01

Brief Summary

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.

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.

Conditions

Kidney Transplant; Complications; Varicella Zoster Virus Infection; Vaccine-Preventable Diseases

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Kidney transplant patients

No interventions assigned to this group

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Technical University of Denmark

OTHER

Sponsor Role: collaborator

Aarhus University Hospital

OTHER

Sponsor Role: collaborator

Odense University Hospital

OTHER

Sponsor Role: collaborator

Susanne Dam Nielsen, MD, DMSc

OTHER

Sponsor Role: lead

Responsible Party

Susanne Dam Nielsen, MD, DMSc

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Susanne D Nielsen, MD, DMSc

Role: PRINCIPAL_INVESTIGATOR

Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet

Søren S Sørensen, MD, DMSc

Role: STUDY_CHAIR

Department of Nephrology, Copenhagen University Hospital - Rigshospitalet

Claus Bistrup, MD, PhD

Role: STUDY_CHAIR

Department of Nephrology, Odense University Hospital

Henrik Birn, MD, PhD, DMSc

Role: STUDY_CHAIR

Department of Nephrology, Aarhus University Hospital

Sine R Hadrup, MSc, PhD

Role: STUDY_CHAIR

Department of Health Technology, Technical University of Denmark

Annemette Hald, RN

Role: STUDY_DIRECTOR

Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet

Sunil K Saini, MSc, PhD

Role: STUDY_DIRECTOR

Department of Health Technology, Technical University of Denmark

Isik S Johansen, MD, DMSc

Role: STUDY_DIRECTOR

Department of Infectious Diseases, Odense University Hospital

Helle Bruunsgaard, MD, PhD, DMSc

Role: STUDY_DIRECTOR

Department of Clinical Immunology, Copenhagen University Hospital - Rigshospitalet

Carsten S Larsen, MD, DMSc

Role: STUDY_DIRECTOR

Department of Infectious Diseases, Aarhus University Hospital

Zitta B Harboe, MD, PhD

Role: STUDY_DIRECTOR

Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital - North Zealand

Moisés A Suarez Zdunek, MD

Role: STUDY_DIRECTOR

Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet

Sebastian R Hamm, BSc.med.

Role: STUDY_DIRECTOR

Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet

Locations

Department of Nephrology, Aarhus University Hospital

Aarhus, , Denmark

Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet

Copenhagen, , Denmark

Department of Nephrology, Copehagen University Hospital - Rigshospitalet

Copenhagen, , Denmark

Department of Health Technology, Technical University of Denmark

Lyngby, , Denmark

Department of Nephrology, Odense University Hospital

Odense, , Denmark

Countries

Denmark

References

Hamm SR, Saini SK, Hald A, Vaaben AV, Pedersen NW, Suarez-Zdunek MA, Harboe ZB, Bruunsgaard H, Johansen IS, Larsen CS, Bistrup C, Birn H, Sorensen SS, Hadrup SR, Nielsen SD. Herpes Virus Infections in Kidney Transplant Patients (HINT) - a prospective observational cohort study. BMC Infect Dis. 2023 Oct 16;23(1):687. doi: 10.1186/s12879-023-08663-5.

Reference Type: DERIVED

PMID: 37845608 (View on PubMed)

Other Identifiers

0073947

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

H-22042603

Identifier Type: -

Identifier Source: org_study_id