Cytomegalovirus InfectionsHISTORYNCT05532540
Herpesvirus Immunology in Solid Organ Transplant Recipients - Liver Transplant Study
An observational study of Cytomegalovirus Infections and Varicella Zoster Virus Infection, run by Susanne Dam Nielsen, MD, DMSc at 3 sites in Denmark.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cytomegalovirus Infections, Varicella Zoster Virus Infection, Liver Transplant; Complications
- How many people
- 80 participants
- Where
- 3 sitesDenmark
- Study dates
- 1 Jan 2023to 1 Jan 2033
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All adults enlisted for liver transplantation at Copenhagen University Hospital - Rigshospitalet (N = around 60 per year) will be invited to participate.
Who may be able to join
- Enlisted for liver transplantation at Copenhagen University Hospital - Rigshospitalet
- Aged 18 years or older
Who cannot join
- Inability to understand the study information
Trial locations and contacts
3 sites in 1 country.
Denmark3 sites
Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet
Copenhagen, 2100
Department of Surgical Gastroenterology, Copenhagen University Hospital - Rigshospitalet
Copenhagen, 2100
Department of Health Technology, Technical University of Denmark
Lyngby, 2800
About this study
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.
Read more
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.
Read the 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.
- 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
- Medical subject headings
- Cytomegalovirus Infections, Varicella Zoster Virus Infection, Chickenpox, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Liver transplant recipients | All adults enlisted for liver transplantation at Copenhagen University Hospital - Rigshospitalet (N = around 60 per year) will be invited to participate regardless of indication for liver transplantation. These participants are expected to undergo a liver transplantation and will continue in the study after the procedure. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1.5 years
Secondary outcomes (3)
Primary CMV infection
Measured: 10 years
VZV reactivation
Measured: 10 years
CMV reactivation
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2022
- Study start1 Jan 2023
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Jan 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cytomegalovirus InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Susanne Dam Nielsen, MD, DMSc
- Sponsor type
- University, hospital or other
- Collaborators
- Technical University of Denmark, Copenhagen University Hospital, Rigshospitalet
- Responsible party
- Sponsor-investigator, Susanne Dam Nielsen, MD, DMSc, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Susanne D Nielsen, Professor, MD, DMSc, Principal investigator, Department of Infectious Diseases, Copenhagen University Hospital - RigshospitaletSine R Hadrup, Professor, MSc, PhD, Principal investigator, Department of Health Technology, Technical University of DenmarkMoises Alberto Suarez Zdunek, MD, Study director, Department of Infectious Diseases, Copenhagen University Hospital - RigshospitaletSebastian R Hamm, BSc, Study director, Department of Infectious Diseases, Copenhagen University Hospital - RigshospitaletAnnemette Hald, RN, Study director, Department of Infectious Diseases, Copenhagen University Hospital - RigshospitaletSunil K Saini, MSc, PhD, Study director, Department of Health Technology, Technical University of DenmarkAllan Rasmussen, MD, Study director, Department of Surgical Gastroenterology, Copenhagen University Hospital - RigshospitaletJens G Hillingsø, MD, PhD, Study director, Department of Surgical Gastroenterology, Copenhagen University Hospital - Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05532540
- Sponsor's protocol ID
- H-22039226
- Other IDs
- 0073947
- Acronym
- HISTORY
- Status last verified
- Aug 2026
- First submitted
- 3 Sep 2022
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Suarez-Zdunek MA, Saini SK, Pedersen CR, Hamm SR, Hald A, Rasmussen A, Hillingso JG, Hadrup SR, Nielsen SD. Herpesvirus immunology in solid organ transplant recipients - liver transplant study (HISTORY): a retrospective and prospective observational cohort study. BMC Infect Dis. 2023 Apr 6;23(1):214. doi: 10.1186/s12879-023-08153-8.
PubMed 37024811
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Herpesvirus Immunology in Solid Organ Transplant Recipients - Liver Transplant Study
- ClinicalTrials.gov ID
- NCT05532540
- Acronym / sponsor ID
- HISTORY / H-22039226
- 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
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Susanne Dam Nielsen, MD, DMScUniversity, hospital or other
- Collaborators
- Technical University of Denmark, Copenhagen University Hospital, Rigshospitalet
- Study start
- 1 Jan 2023 (actual)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 1 Jan 2033 (estimated)
- First posted
- 8 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Liver transplant recipients | – | –All adults enlisted for liver transplantation at Copenhagen University Hospital - Rigshospitalet (N = around 60 per year) will be invited to participate regardless of indication for liver transplantation. These participants are expected to undergo a liver transplantation and will continue in the study after the procedure. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All adults enlisted for liver transplantation at Copenhagen University Hospital - Rigshospitalet (N = around 60 per year) will be invited to participate.
Key inclusion criteria (2 listed)
- Enlisted for liver transplantation at Copenhagen University Hospital - Rigshospitalet
- Aged 18 years or older
Key exclusion criteria (1 listed)
- Inability to understand the study information
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Frequency, phenotype and function of CMV- and VZV-specific T cells (descriptive)
Time frame: 1.5 years
Including: TCR clonotypes, cell surface markers and cytokine profile of T cell populations specific towards immunodominant CMV and VZV epitopes.
3 secondary outcomes
Primary CMV infection
Time frame: 10 years
VZV reactivation
Time frame: 10 years
CMV reactivation
Time frame: 10 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2026.
- Derived from this study: PubMed 37024811Suarez-Zdunek MA, Saini SK, Pedersen CR, Hamm SR, Hald A, Rasmussen A, Hillingso JG, Hadrup SR, Nielsen SD. Herpesvirus immunology in solid organ transplant recipients - liver transplant study (HISTORY): a retrospective and prospective observational cohort study. BMC Infect Dis. 2023 Apr 6;23(1):214. doi: 10.1186/s12879-023-08153-8.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susanne D Nielsen, Professor, MD, DMSc principal investigator
Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet
Sine R Hadrup, Professor, MSc, PhD principal investigator
Department of Health Technology, Technical University of Denmark
Moises Alberto Suarez Zdunek, MD study director
Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cytomegalovirus Infections and Varicella Zoster Virus Infection, run by Susanne Dam Nielsen, MD, DMSc at 3 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency, phenotype and function of CMV- and VZV-specific T cells (descriptive) (time frame: 1.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05532540, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2026.