Herpesvirus Immunology in Solid Organ Transplant Recipients - Liver Transplant Study

Cytomegalovirus Infections Clinical Trial

— HISTORY  

Official title:

Herpesvirus Immunology in Solid Organ Transplant Recipients - Liver Transplant Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05532540
• Other study ID #: H-22039226
• Secondary ID: 0073947
• Status: Recruiting
• Start date: January 1, 2023
• Est. completion date: January 1, 2033

Study information

• Verified date: April 2024
• Source: Rigshospitalet, Denmark
• Contact: Susanne D Nielsen, Professor, MD, DMSc
• Phone: +4535457756
• Email: susanne.dam.poulsen[@]regionh.dk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: January 1, 2033
• Est. primary completion date: January 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Enlisted for liver transplantation at Copenhagen University Hospital - Rigshospitalet

• Aged 18 years or older

Exclusion Criteria:

• Inability to understand the study information

Related Conditions & MeSH terms

• Communicable Diseases
• Cytomegalovirus Infections
• Herpes Zoster
• Infections
• Liver Transplant; Complications
• Varicella Zoster Virus Infection

Locations

Country	Name	City	State
Denmark	Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet	Copenhagen
Denmark	Department of Surgical Gastroenterology, Copenhagen University Hospital - Rigshospitalet	Copenhagen
Denmark	Department of Health Technology, Technical University of Denmark	Lyngby

Sponsors (3)

Lead Sponsor	Collaborator
Susanne Dam Nielsen, MD, DMSc	Rigshospitalet, Denmark, Technical University of Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency, phenotype and function of CMV- and VZV-specific T cells (descriptive)	Including: TCR clonotypes, cell surface markers and cytokine profile of T cell populations specific towards immunodominant CMV and VZV epitopes.	1.5 years
Secondary	Primary CMV infection		10 years
Secondary	VZV reactivation		10 years
Secondary	CMV reactivation		10 years