Epstein-Barr Virus (EBV) InfectionNCT05127980
Occurrence of Antibodies Cross-reacting With Autoantigens in Primary EBV Infection
An observational study of Epstein-Barr Virus (EBV) Infection, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial summary
The aim of this study is to assess the occurrence of antibodies cross-reacting with autoantigens that have been detected in the context of SLE in patients with primary EBV infection over time compared to a control group. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Epstein-Barr Virus (EBV) Infection
- What is being tested?
- Data collection: Participant characteristics (Illness course, complications of primary EBV infection and provided treatments), Data collection: blood samples (analysed for EBV serology, auto-antibody-testing/biobanking, RNA expression analyses, procalcitonin) and Data collection: Patient reported outcome (Fatigue questionnaires)
- How many people
- 80 participants
- Where
- 1 siteSwitzerland
- Study dates
- 15 Oct 2021to Dec 2026
- 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: Inpatients and outpatients with symptoms of infectious mononucleosis (IM) or a sore throat who are treated at the University Hospital of Basel will be approached.
Who may be able to join
- Participants fulfilling all of the following inclusion criteria are eligible for the infectious mononucleosis (IM) group:
- Informed consent as documented by signature
- Confirmed primary EBV infection as confirmed by the treating clinician and defined by:
- Compatible clinical (infectious mononucleosis symptoms including but not limited to malaise, headache, fever, tonsillitis, pharyngitis, cervical lymph nodes enlargement) and laboratory picture (lymphocyte count elevation, LUC cells, reactive lymphocytes in manual differential, elevated liver enzymes; of note, not all typically described features have to be fulfilled)
- AND
- serology compatible with primary EBV infection (anti-EBNA IgG negative, anti-VCA IgG negative, anti-VCA IgM positive OR anti-EBNA IgG negative, anti-VCA IgG positive, anti- VCA IgM positive).
Show all 11Show fewer
- Participants fulfilling all of the following inclusion criteria will be eligible for the control group:
- Informed consent as documented by signature.
- one of the following:
- Clinical picture of upper respiratory tract infection (including but not limited to tonsillitis/pharyngitis, malaise, headache, cough, rhinitis, cervical node enlargement)
- confirmed primary Cytomegalovirus (CMV) infection (an optimal control group; however, the number of patients with a diagnosis of primary CMV infection is limited).
Who cannot join
- Suspicion/diagnosis of IM as per judgement of the treating clinician (control group only); this individual may be eligible later for the IM group if primary EBV infection is confirmed, subsequently.
- Immunosuppression (broadly defined as primary/secondary immunodeficiency or treatment with an immunosuppressive medication including ≥ 10mg prednisone equivalent).
- History of autoimmune disease (e.g. SLE, vasculitis etc.)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site, 1 recruiting
- Recruiting
University Hospital Basel, Division of Internal Medicine
Basel, 4031
Michael Osthoff, PD Dr. med., +41 61 328 68 28, michael.osthoff@usb.ch
Samuel Etienne, +41 61 556 5248, samuel.etienne@usb.ch
About this study
Official title: Occurrence of Antibodies Cross-reacting With Autoantigens in Primary EBV Infection - a Longitudinal, Observational Study
The aim of this study is to assess the occurrence of antibodies cross-reacting with autoantigens that have been detected in the context of SLE in patients with primary EBV infection over time compared to a control group. It is to establish a biobank of patients with primary EBV infection allowing to longitudinally analyze the immune response and its accompanying inflammatory processes with focus on the occurrence of antibodies cross-reacting with autoantigens associated with SLE and other autoimmune diseases.
Substudies will analyze
- characteristics of primary EBV infection patients treated with antibiotics in comparison to patients treated without antibiotics and outcomes of these treatment regimens (occurrence of acute complications such as peritonsillar abscess (PTA) or need for tonsillectomy, frequency of fatigue or symptoms associated with chronic fatigue syndrome).
- Procalcitonin (PCT) concentrations in primary EBV infection compared to control patients with similar symptoms and its association with disease severity and local complications.
- the occurrence of fatigue and symptoms associated with chronic fatigue syndrome 6 and 12 months after primary EBV infection.
Read the detailed description
Epstein-Barr Virus (EBV) is a lymphotropic herpes virus and the causative agent of infectious mononucleosis (IM). The course of EBV infection is determined by the virus load and an individuals' immune system state, which in turn is determined by the person's gene composition, other infection history and several environmental factors, which all may influence the immune capacity of a person to various degrees. Many diseases are known to be associated with EBV infection, among those diseases are systemic autoimmune diseases. With regard to EBV, prior infection with the virus seems to be of crucial importance for the development of systemic lupus erythematosus (SLE). Autoantibodies against complement C1q (anti-C1q) can be induced in vivo by the Epstein-Barr virus-derived antigenic site 'EBNA348' (also being part of the C-terminal EBNA-1).
This study is to analyze whether the primary infection with EBV (leading to IM and antibodies targeting EBV-derived antigens including antibodies against EBNA-1) leads to an at least transient occurrence of antibodies against the virus that have the potential to cross-react with autoantigens as described in patients with systemic autoimmune diseases (e.g. complement C1q, dsDNA, Ro, Sm, MOG, NF186 and others). The advantage of an analysis of patients with primary infection is that the de novo synthesis of antibodies against the virus will allow to determine the time-dependent evolution of the antibody repertoire against the virus as well as against a number of autoantigens.
- Conditions
- Epstein-Barr Virus (EBV) Infection
- Being tested
- Data collection: Participant characteristics (Illness course, complications of primary EBV infection and provided treatments), Data collection: blood samples (analysed for EBV serology, auto-antibody-testing/biobanking, RNA expression analyses, procalcitonin), Data collection: Patient reported outcome (Fatigue questionnaires)
- Keywords
- Infectious mononucleosis (IM), Viral capsid antigen (VCA), EBV nucleic antigen (EBNA), Systemic lupus erythematosus (SLE), Chronic fatigue syndrome (CFS), cross-reacting antibodies, molecular mimicry
- Medical subject headings
- Epstein-Barr Virus Infections, Infections, Infectious Mononucleosis, Lupus Erythematosus, Systemic, Fatigue Syndrome, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Data collection: Participant characteristics (Illness course, complications of primary EBV infection and provided treatments)Other
Data collection: Participant characteristics (Illness course, complications of primary EBV infection and provided treatments) during 12 months (baseline visit and follow-up visits at 3, 6 and 12 months).
Data collection: blood samples (analysed for EBV serology, auto-antibody-testing/biobanking, RNA expression analyses, procalcitonin)Other
Data collection: blood samples (analysed for EBV serology, auto-antibody-testing/biobanking, RNA expression analyses, procalcitonin) during 12 months (baseline visit and follow-up visits at 3, 6 and 12 months).
Data collection: Patient reported outcome (Fatigue questionnaires)Other
Data collection: Patient reported outcome (Fatigue questionnaires) at 6 and 12 months.
| Study group | Role | What they receive |
|---|---|---|
| patients with confirmed primary EBV infection | 40 patients with confirmed primary EBV infection as confirmed by the treating clinician and defined by:
- Compatible clinical (infectious mononucleosis symptoms including but not limited to malaise, headache, fever, tonsillitis, pharyngitis, cervical lymph nodes enlargement) and laboratory picture (lymphocyte count elevation, LUC cells, reactive lymphocytes in manual differential, elevated liver enzymes; of note, not all typically described features have to be fulfilled)
AND
- serology compatible with primary EBV infection (anti-EBNA IgG negative, anti-VCA IgG negative, anti-VCA IgM positive OR anti-EBNA IgG negative, anti-VCA IgG positive, anti- VCA IgM positive) Receives: Other: Data collection: Participant characteristics (Illness course, complications of primary EBV infection and provided treatments); Other: Data collection: blood samples (analysed for EBV serology, auto-antibody-testing/biobanking, RNA expression analyses, procalcitonin); Other: Data collection: Patient reported outcome (Fatigue questionnaires) | |
| control patients | 40 control patients (Clinical picture of upper respiratory tract infection (including but not limited to tonsillitis/pharyngitis, malaise, headache, cough, rhinitis, cervical node enlargement)) and/ or confirmed primary Cytomegalovirus (CMV) infection Receives: Other: Data collection: Participant characteristics (Illness course, complications of primary EBV infection and provided treatments); Other: Data collection: blood samples (analysed for EBV serology, auto-antibody-testing/biobanking, RNA expression analyses, procalcitonin); Other: Data collection: Patient reported outcome (Fatigue questionnaires) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in occurrence of antibodies cross-reacting with autoantigens in patients with primary EBV infection
Change in occurrence of antibodies cross-reacting with autoantigens in patients with primary EBV infection compared to a control group.
Measured: at Visit 2 (day 1 (+ 1 day)), Visit 3 (3 months +/- 21 days), Visit 4 (6 months +/- 1 month) and Visit 5 (12 months +/-2 months)
Secondary outcomes (5)
Change in RNA expression profiles of peripheral blood cells
Change in RNA expression profiles of peripheral blood cells in patients with primary EBV infection over time and compared to a control group.
Measured: at Visit 2 (day 1 (+ 1 day)), Visit 3 (3 months +/- 21 days), Visit 4 (6 months +/- 1 month) and Visit 5 (12 months +/-2 months)
Change in Fatigue Assessment Scale (FAS)
The total score ranges from 10 to 50. A total FAS score < 22 indicates no fatigue, a score ≥ 22 indicates fatigue.
Measured: at month 6 and at month 12
Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire
FACIT-F is a 13-item instrument designed to assess fatigue/ tiredness and its impact on daily activities and functioning in a number of chronic diseases. The instrument includes items such as tiredness, weakness, listlessness, lack of energy, and the impact of these feelings on daily functioning (e.g., sleeping, and social activities). Items are scored on a 0 - 4 response scale with anchors ranging from "Not at all" to "Very much so" (in which higher scores represent better functioning or less fatigue).
Measured: at month 6 and at month 12
Change in Procalcitonin (PCT) (Substudy Procalcitonin)
Change in PCT compared in primary EBV infection patients with different disease severities and different treatment modalities (in particular if they received antibiotics or not), and in comparison to a control group (with mostly (viral) upper respiratory tract infection or primary CMV infection); In IM and control patients admitted to hospital, blood will be collected for PCT measurement
Measured: on day 1 and day 3 (+/-1 day)
Occurrence of acute complications such as PTA or need for tonsillectomy
Occurrence of acute complications such as PTA or need for tonsillectomy in primary EBV infection patients treated with antibiotics in comparison to patients treated without antibiotics
Measured: at Visit 2 (day 1 (+ 1 day)) and Visit 3 (3 months +/- 21 days),
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2021
- Study start15 Oct 2021
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Epstein-Barr Virus (EBV) InfectionStudies 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
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael Osthoff, PD Dr. med., Principal investigator, University Hospital Basel, Division of Internal Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05127980
- Sponsor's protocol ID
- 2021-01338; am21Osthoff2
- Status last verified
- Feb 2025
- First submitted
- 25 Oct 2021
- Last updated
- 25 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Occurrence of Antibodies Cross-reacting With Autoantigens in Primary EBV Infection - a Longitudinal, Observational Study
- ClinicalTrials.gov ID
- NCT05127980
- Acronym / sponsor ID
- 2021-01338; am21Osthoff2
- Conditions
- Epstein-Barr Virus (EBV) Infection
- Keywords
- Infectious mononucleosis (IM), Viral capsid antigen (VCA), EBV nucleic antigen (EBNA), Systemic lupus erythematosus (SLE), Chronic fatigue syndrome (CFS), cross-reacting antibodies, molecular mimicry
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- 15 Oct 2021 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 19 Nov 2021 (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.
The aim of this study is to assess the occurrence of antibodies cross-reacting with autoantigens that have been detected in the context of SLE in patients with primary EBV infection over time compared to a control group. It is to establish a biobank of patients with primary EBV infection allowing to longitudinally analyze the immune response and its accompanying inflammatory processes with focus on the occurrence of antibodies cross-reacting with autoantigens associated with SLE and other autoimmune diseases.
Substudies will analyze
- characteristics of primary EBV infection patients treated with antibiotics in comparison to patients treated without antibiotics and outcomes of these treatment regimens (occurrence of acute complications such as peritonsillar abscess (PTA) or need for tonsillectomy, frequency of fatigue or symptoms associated with chronic fatigue syndrome).
- Procalcitonin (PCT) concentrations in primary EBV infection compared to control patients with similar symptoms and its association with disease severity and local complications.
- the occurrence of fatigue and symptoms associated with chronic fatigue syndrome 6 and 12 months after primary EBV infection.
Detailed description
Epstein-Barr Virus (EBV) is a lymphotropic herpes virus and the causative agent of infectious mononucleosis (IM). The course of EBV infection is determined by the virus load and an individuals' immune system state, which in turn is determined by the person's gene composition, other infection history and several environmental factors, which all may influence the immune capacity of a person to various degrees. Many diseases are known to be associated with EBV infection, among those diseases are systemic autoimmune diseases. With regard to EBV, prior infection with the virus seems to be of crucial importance for the development of systemic lupus erythematosus (SLE). Autoantibodies against complement C1q (anti-C1q) can be induced in vivo by the Epstein-Barr virus-derived antigenic site 'EBNA348' (also being part of the C-terminal EBNA-1).
This study is to analyze whether the primary infection with EBV (leading to IM and antibodies targeting EBV-derived antigens including antibodies against EBNA-1) leads to an at least transient occurrence of antibodies against the virus that have the potential to cross-react with autoantigens as described in patients with systemic autoimmune diseases (e.g. complement C1q, dsDNA, Ro, Sm, MOG, NF186 and others). The advantage of an analysis of patients with primary infection is that the de novo synthesis of antibodies against the virus will allow to determine the time-dependent evolution of the antibody repertoire against the virus as well as against a number of autoantigens.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| patients with confirmed primary EBV infection | – | Other: Data collection: Participant characteristics (Illness course, complications of primary EBV infection and provided treatments), Other: Data collection: blood samples (analysed for EBV serology, auto-antibody-testing/biobanking, RNA expression analyses, procalcitonin), Other: Data collection: Patient reported outcome (Fatigue questionnaires)40 patients with confirmed primary EBV infection as confirmed by the treating clinician and defined by: - Compatible clinical (infectious mononucleosis symptoms including but not limited to malaise, headache, fever, tonsillitis, pharyngitis, cervical lymph nodes enlargement) and laboratory picture (lymphocyte count elevation, LUC cells, reactive lymphocytes in manual differential, elevated liver enzymes; of note, not all typically described features have to be fulfilled) AND - serology compatible with primary EBV infection (anti-EBNA IgG negative, anti-VCA IgG negative, anti-VCA IgM positive OR anti-EBNA IgG negative, anti-VCA IgG positive, anti- VCA IgM positive) |
| control patients | – | Other: Data collection: Participant characteristics (Illness course, complications of primary EBV infection and provided treatments), Other: Data collection: blood samples (analysed for EBV serology, auto-antibody-testing/biobanking, RNA expression analyses, procalcitonin), Other: Data collection: Patient reported outcome (Fatigue questionnaires)40 control patients (Clinical picture of upper respiratory tract infection (including but not limited to tonsillitis/pharyngitis, malaise, headache, cough, rhinitis, cervical node enlargement)) and/ or confirmed primary Cytomegalovirus (CMV) infection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Inpatients and outpatients with symptoms of infectious mononucleosis (IM) or a sore throat who are treated at the University Hospital of Basel will be approached.
Key inclusion criteria (11 listed)
- Participants fulfilling all of the following inclusion criteria are eligible for the infectious mononucleosis (IM) group:
- Informed consent as documented by signature
- Confirmed primary EBV infection as confirmed by the treating clinician and defined by:
- Compatible clinical (infectious mononucleosis symptoms including but not limited to malaise, headache, fever, tonsillitis, pharyngitis, cervical lymph nodes enlargement) and laboratory picture (lymphocyte count elevation, LUC cells, reactive lymphocytes in manual differential, elevated liver enzymes; of note, not all typically described features have to be fulfilled)
- AND
Key exclusion criteria (3 listed)
- Suspicion/diagnosis of IM as per judgement of the treating clinician (control group only); this individual may be eligible later for the IM group if primary EBV infection is confirmed, subsequently.
- Immunosuppression (broadly defined as primary/secondary immunodeficiency or treatment with an immunosuppressive medication including ≥ 10mg prednisone equivalent).
- History of autoimmune disease (e.g. SLE, vasculitis etc.)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Data collection: Participant characteristics (Illness course, complications of primary EBV infection and provided treatments)Data collection: Participant characteristics (Illness course, complications of primary EBV infection and provided treatments) during 12 months (baseline visit and follow-up visits at 3, 6 and 12 months). | Other | control patients, patients with confirmed primary EBV infection |
| Data collection: blood samples (analysed for EBV serology, auto-antibody-testing/biobanking, RNA expression analyses, procalcitonin)Data collection: blood samples (analysed for EBV serology, auto-antibody-testing/biobanking, RNA expression analyses, procalcitonin) during 12 months (baseline visit and follow-up visits at 3, 6 and 12 months). | Other | control patients, patients with confirmed primary EBV infection |
| Data collection: Patient reported outcome (Fatigue questionnaires)Data collection: Patient reported outcome (Fatigue questionnaires) at 6 and 12 months. | Other | control patients, patients with confirmed primary EBV infection |
Primary outcome
Change in occurrence of antibodies cross-reacting with autoantigens in patients with primary EBV infection
Time frame: at Visit 2 (day 1 (+ 1 day)), Visit 3 (3 months +/- 21 days), Visit 4 (6 months +/- 1 month) and Visit 5 (12 months +/-2 months)
Change in occurrence of antibodies cross-reacting with autoantigens in patients with primary EBV infection compared to a control group.
5 secondary outcomes
Change in RNA expression profiles of peripheral blood cells
Time frame: at Visit 2 (day 1 (+ 1 day)), Visit 3 (3 months +/- 21 days), Visit 4 (6 months +/- 1 month) and Visit 5 (12 months +/-2 months)
Change in Fatigue Assessment Scale (FAS)
Time frame: at month 6 and at month 12
Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire
Time frame: at month 6 and at month 12
Change in Procalcitonin (PCT) (Substudy Procalcitonin)
Time frame: on day 1 and day 3 (+/-1 day)
Occurrence of acute complications such as PTA or need for tonsillectomy
Time frame: at Visit 2 (day 1 (+ 1 day)) and Visit 3 (3 months +/- 21 days),
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 25 Feb 2025.
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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.
Michael Osthoff, PD Dr. med. principal investigator
University Hospital Basel, Division of Internal Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Epstein-Barr Virus (EBV) Infection, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
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 11 inclusion and 3 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: looking for participants now, as of the sponsor's last update on 25 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. 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?
Contact Michael Osthoff, PD Dr. med. (+41 61 328 68 28, michael.osthoff@usb.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in occurrence of antibodies cross-reacting with autoantigens in patients with primary EBV infection (time frame: at Visit 2 (day 1 (+ 1 day)), Visit 3 (3 months +/- 21 days), Visit 4 (6 months +/- 1 month) and Visit 5 (12 months +/-2 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Feb 2025.