Clinical trial NCT05532540: Herpesvirus Immunology in Solid Organ Transplant Recipients - Liver Transplant Study
Official title: Herpesvirus Immunology in Solid Organ Transplant Recipients - Liver Transplant Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Cytomegalovirus Infections
Varicella Zoster Virus Infection
Liver Transplant; Complications
Keywords: Cytomegalovirus
Herpesvirus 3, Human
Liver Transplantation
T-Lymphocytes
Inflammation
Immunodominant Epitopes
Major Histocompatibility Complex
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Technical University of Denmark
name: Rigshospitalet, Denmark
First posted: 2022-09-08
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All adults enlisted for liver transplantation at Copenhagen University Hospital - Rigshospitalet (N = around 60 per year) will be invited to participate.

Brief summary: Liver transplantation is the only curative treatment of end-stage liver disease, and every year, around 60 patients undergo liver transplantation in Denmark. Immunosuppressive therapy is necessary to avoid rejection of the transplanted organ.

Over 90% of adults have been infected with at least one herpesvirus, and it is characteristic for herpesviruses that after a first-time infection, the virus remains dormant in the body and may reactivate, particularly if the host is immunosuppressed. An effective immune response against reactivation depends highly on T cells, but T cells are suppressed by immunosuppressive drugs given to organ transplant recipients. Infections caused by herpesviruses are therefore very common in organ transplant recipients, and particularly two herpesviruses, cytomegalovirus (CMV) and varicella-zoster virus (VZV) pose challenges after transplantation.

CMV causes significant morbidity in transplant recipients, contributes to increased mortality and may contribute to loss of the transplanted organ. CMV infections occur in around 40% of liver transplant recipients within a year of transplantation. VZV causes chickenpox at first-time infection and shingles at reactivation. VZV is the second-most common infection in transplant recipients and occurs in around 9% of liver transplant recipients each year. Organ transplant recipients are at higher risk for disseminated disease with complications compared to immunocompetent persons.

A limited number of drugs exist that reduce the risk of and treat CMV infection, but they may cause significant adverse events, and drug resistance is emerging. To avoid CMV infection, some liver transplant recipients receive prophylactic therapy, but due to toxicity, new treatment modalities are warranted. This requires knowledge about herpesvirus specific T cell function in liver transplant recipients, which currently is limited.

The aim of this study is to provide an in-depth description of the protective immune response and immunological risk factors for CMV and VZV infections in liver transplant recipients and to identify patients at high risk in order to provide a platform for future treatment modalities against CMV and VZV infections in liver transplant recipients.

Detailed description: The Herpesvirus Immunology in Solid Organ Transplant Recipients - Liver Transplant Study (HISTORY) is a prospective cohort study that aims to provide in-depth characterisation of the protective immune response and immunological risk factors for CMV and VZV infections in liver transplant recipients and to identify patients at high risk of infection based on clinical and immunological risk factors. All adult patients enlisted for liver transplantation at the Copenhagen University Hospital - Rigshospitalet will be invited to participate regardless of indication for transplantation.

At study entry, participants will fill out a questionnaire regarding health and medication use. Blood samples will be collected at study entry when enlisted for transplantation, at pre-defined intervals after transplantation, and if primary infection with or reactivation of CMV or VZV occurs during follow-up. Health data will be collected from hospital records and national registries.

Blood samples will be separated into peripheral blood mononuclear cells (PBMC) and plasma and stored in a biobank for analysis of PBMC phenotype and function, concentrations of inflammatory markers and mediators, CMV and VZV viral load and serology and other in-depth immunological analyses. Analyses will be performed at the Technical University of Denmark.

Eligibility criteria: Inclusion Criteria:

* Enlisted for liver transplantation at Copenhagen University Hospital - Rigshospitalet
* Aged 18 years or older

Exclusion Criteria:

* Inability to understand the study information

Primary outcomes:
measure: Frequency, phenotype and function of CMV- and VZV-specific T cells (descriptive)
timeFrame: 1.5 years
Secondary outcomes:
measure: Primary CMV infection
timeFrame: 10 years
measure: VZV reactivation
timeFrame: 10 years
measure: CMV reactivation
timeFrame: 10 years
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet
city: Copenhagen
country: Denmark
facility: Department of Surgical Gastroenterology, Copenhagen University Hospital - Rigshospitalet
city: Lyngby
country: Denmark
facility: Department of Health Technology, Technical University of Denmark
Study officials:
affiliation: Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet
name: Susanne D Nielsen, Professor, MD, DMSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Health Technology, Technical University of Denmark
name: Sine R Hadrup, Professor, MSc, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet
name: Moises Alberto Suarez Zdunek, MD
role: STUDY_DIRECTOR
affiliation: Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet
name: Sebastian R Hamm, BSc
role: STUDY_DIRECTOR
affiliation: Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet
name: Annemette Hald, RN
role: STUDY_DIRECTOR
affiliation: Department of Health Technology, Technical University of Denmark
name: Sunil K Saini, MSc, PhD
role: STUDY_DIRECTOR
affiliation: Department of Surgical Gastroenterology, Copenhagen University Hospital - Rigshospitalet
name: Allan Rasmussen, MD
role: STUDY_DIRECTOR
affiliation: Department of Surgical Gastroenterology, Copenhagen University Hospital - Rigshospitalet
name: Jens G Hillingsø, MD, PhD
role: STUDY_DIRECTOR
affiliation: Department of Surgical Gastroenterology, Copenhagen University Hospital - Rigshospitalet
name: Christian R Pedersen, MD
role: STUDY_DIRECTOR
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