Epstein-Barr Virus InfectionsNCT03374566
Immunodeficiency for Severe Epstein-Barr Virus Infection
An observational study of Epstein-Barr Virus Infections and Immunodeficiency, run by Children's Hospital of Fudan University at 1 site in China.
Trial summary
The purpose of this study is to investigate the immune responses associated with Epstein-Barr virus infections, and to find out the possible immunodeficiency that may be linked to severe Epstein-Barr virus infections. Read more about this study
- Who is it for?
- Ages 1 day to 18 years
- Conditions the study is for
- Epstein-Barr Virus Infections, Immunodeficiency
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- 1 Dec 2017to 1 Feb 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
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 1 day to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: We will evaluate immunodeficiency incidence in patients with severe EBV infection
Who may be able to join
- 1. Age：birth to 18 years 2. Severe Epstein-Barr Virus infection
Who cannot join
- 1. Lack of parental consent
Trial locations and contacts
1 site in 1 country.
China1 site
Children's Hospital of Fudan University
Shanghai, Shanghai Municipality
About this study
Official title: Screening for Immunodeficiency Diseases in Patients With Severe Epstein-Barr Virus Infection
The purpose of this study is to investigate the immune responses associated with Epstein-Barr virus infections, and to find out the possible immunodeficiency that may be linked to severe Epstein-Barr virus infections.
Read the detailed description
Epstein-Barr virus (EBV) belongs to herpesviridae family, which infects more than 90% of the population. EBV infection is usually asymptomatic and establishes lifelong persistence in the host, although primary infection later than adolescence frequently results in infectious mononucleosis (IM). Rarely, individuals may develop a subgroup of EBV-associated life threatening complications (including liver dysfunction, haemophagocytosis and malignancy).
Although EBV-infected B cells have the potential for proliferation, they are effectively removed by the EBV-specific cytotoxic T cells (CTL). In the immunocompetent hosts, natural killer (NK) cells and antigen-specific cluster designation 8 (CD8+) T-cells play an important role in inhibiting progression of primary EBV infection by granule-mediated cytotoxicity. The immune system is necessary to control the virus-induced transformation and the B-cell unlimited proliferation.
Primary immunodeficiency are a heterogeneous group of hereditary diseases that are associated with compromised immune responses. There are a number of immunodeficiency resulting in inability of immune system to control EBV infection, for example X-linked Lymphoproliferative disease (XLP)/signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) deficiency, X-linked inhibitor of apoptosis (XIAP) deficiency, cluster of differentiation antigen 27 (CD27) deficiency, interleukin-2-inducible T-cell kinase (ITK) deficiency, and so on. Whereas, some other clinical states associated with EBV-susceptibility remain largely unknown. Rare EBV-infected individuals without apparent immunodeficiency also present with persistent IM-like symptoms, hepatosplenomegaly, liver dysfunction, lymphadenopathy and haemophagocytic lymphohistiocytosis.
Patients presenting with severe EBV infections should be focused on early identification of a possible primary immunodeficiency or a chronic active EBV infection clinical condition (CAEBV) and haemophagocytic lymphohistiocytosis(HLH). Immunological phenotyping of NK-, T- and B-cell differentiation, and functional assays including cytotoxic cell killing function and cytotoxic granule release, provide a useful identification for clinical conditions inability to control EBV infections. Genomic DNA is isolated from peripheral blood mononuclear cells and will be amplified to screen for possible immunodeficiency.
The reasons for those patients inability to control the EBV infection are still unknown. However no effective treatment is currently available, those patients might benefit from early hematopoietic stem cell transplantation (HSCT). Through this study, we hope to identify the unknown immune immunodeficiency and pathophysiology of those EBV-associated conditions. The investigators propose to help make early diagnosis and develop effective therapies.
- Conditions
- Epstein-Barr Virus Infections, Immunodeficiency
- Keywords
- Epstein-Barr Virus Infections, Immunodeficiency, Screening, Immunologic Function
- Medical subject headings
- Epstein-Barr Virus Infections, Immunologic Deficiency Syndromes
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 |
|---|---|---|
| Screened patients | Immunodeficiency screening: Heparinized peripheral blood is obtained from patients with severe EBV infections for immunological function assays and genetic analysis, when current screening is performed after parents' information and consent. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immunodeficiency incidence in patients with severe EBV infection
We will investigate immunodeficiency incidence in patients with severe EBV infection.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2017
- Study start1 Dec 2017
- Primary completion30 Oct 2022
- Study completion1 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Epstein-Barr Virus InfectionsStudies of the same condition, open and under way.
- More trials run by Children's Hospital of Fudan UniversityThe sponsor's other registered studies.
- 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
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jinqiao Sun, Children's Hospital of Fudan University
- Investigators
- Jinqiao Sun, Ph.D.,M.D, Principal investigator, Children's Hospital of Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03374566
- Sponsor's protocol ID
- EBV
- Status last verified
- Feb 2023
- First submitted
- 12 Dec 2017
- Last updated
- 9 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Worth AJ, Houldcroft CJ, Booth C. Severe Epstein-Barr virus infection in primary immunodeficiency and the normal host. Br J Haematol. 2016 Nov;175(4):559-576. doi: 10.1111/bjh.14339. Epub 2016 Oct 17.
PubMed 27748521Shabani M, Nichols KE, Rezaei N. Primary immunodeficiencies associated with EBV-Induced lymphoproliferative disorders. Crit Rev Oncol Hematol. 2016 Dec;108:109-127. doi: 10.1016/j.critrevonc.2016.10.014. Epub 2016 Nov 2.
PubMed 27931829Palendira U, Rickinson AB. Primary immunodeficiencies and the control of Epstein-Barr virus infection. Ann N Y Acad Sci. 2015 Nov;1356:22-44. doi: 10.1111/nyas.12937. Epub 2015 Sep 28.
PubMed 26415106Taylor GS, Long HM, Brooks JM, Rickinson AB, Hislop AD. The immunology of Epstein-Barr virus-induced disease. Annu Rev Immunol. 2015;33:787-821. doi: 10.1146/annurev-immunol-032414-112326. Epub 2015 Feb 11.
PubMed 25706097Fujiwara S, Kimura H, Imadome K, Arai A, Kodama E, Morio T, Shimizu N, Wakiguchi H. Current research on chronic active Epstein-Barr virus infection in Japan. Pediatr Int. 2014 Apr;56(2):159-66. doi: 10.1111/ped.12314.
PubMed 24528553Eligio P, Delia R, Valeria G. EBV Chronic Infections. Mediterr J Hematol Infect Dis. 2010 Aug 10;2(1):e2010022. doi: 10.4084/MJHID.2010.022.
PubMed 21415952
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Screening for Immunodeficiency Diseases in Patients With Severe Epstein-Barr Virus Infection
- ClinicalTrials.gov ID
- NCT03374566
- Acronym / sponsor ID
- EBV
- Conditions
- Epstein-Barr Virus Infections, Immunodeficiency
- Keywords
- Epstein-Barr Virus Infections, Immunodeficiency, Screening, Immunologic Function
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Children's Hospital of Fudan UniversityUniversity, hospital or other
- Study start
- 1 Dec 2017 (actual)
- Primary completion
- 30 Oct 2022 (actual)
- Study completion
- 1 Feb 2023 (actual)
- First posted
- 15 Dec 2017 (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 purpose of this study is to investigate the immune responses associated with Epstein-Barr virus infections, and to find out the possible immunodeficiency that may be linked to severe Epstein-Barr virus infections.
Detailed description
Epstein-Barr virus (EBV) belongs to herpesviridae family, which infects more than 90% of the population. EBV infection is usually asymptomatic and establishes lifelong persistence in the host, although primary infection later than adolescence frequently results in infectious mononucleosis (IM). Rarely, individuals may develop a subgroup of EBV-associated life threatening complications (including liver dysfunction, haemophagocytosis and malignancy).
Although EBV-infected B cells have the potential for proliferation, they are effectively removed by the EBV-specific cytotoxic T cells (CTL). In the immunocompetent hosts, natural killer (NK) cells and antigen-specific cluster designation 8 (CD8+) T-cells play an important role in inhibiting progression of primary EBV infection by granule-mediated cytotoxicity. The immune system is necessary to control the virus-induced transformation and the B-cell unlimited proliferation.
Primary immunodeficiency are a heterogeneous group of hereditary diseases that are associated with compromised immune responses. There are a number of immunodeficiency resulting in inability of immune system to control EBV infection, for example X-linked Lymphoproliferative disease (XLP)/signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) deficiency, X-linked inhibitor of apoptosis (XIAP) deficiency, cluster of differentiation antigen 27 (CD27) deficiency, interleukin-2-inducible T-cell kinase (ITK) deficiency, and so on. Whereas, some other clinical states associated with EBV-susceptibility remain largely unknown. Rare EBV-infected individuals without apparent immunodeficiency also present with persistent IM-like symptoms, hepatosplenomegaly, liver dysfunction, lymphadenopathy and haemophagocytic lymphohistiocytosis.
Patients presenting with severe EBV infections should be focused on early identification of a possible primary immunodeficiency or a chronic active EBV infection clinical condition (CAEBV) and haemophagocytic lymphohistiocytosis(HLH). Immunological phenotyping of NK-, T- and B-cell differentiation, and functional assays including cytotoxic cell killing function and cytotoxic granule release, provide a useful identification for clinical conditions inability to control EBV infections. Genomic DNA is isolated from peripheral blood mononuclear cells and will be amplified to screen for possible immunodeficiency.
The reasons for those patients inability to control the EBV infection are still unknown. However no effective treatment is currently available, those patients might benefit from early hematopoietic stem cell transplantation (HSCT). Through this study, we hope to identify the unknown immune immunodeficiency and pathophysiology of those EBV-associated conditions. The investigators propose to help make early diagnosis and develop effective therapies.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Screened patients | – | –Immunodeficiency screening: Heparinized peripheral blood is obtained from patients with severe EBV infections for immunological function assays and genetic analysis, when current screening is performed after parents' information and consent. |
Who may qualify
- Ages
- 1 day to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- We will evaluate immunodeficiency incidence in patients with severe EBV infection
Key inclusion criteria (1 listed)
- 1. Age：birth to 18 years 2. Severe Epstein-Barr Virus infection
Key exclusion criteria (1 listed)
- 1. Lack of parental consent
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
Immunodeficiency incidence in patients with severe EBV infection
Time frame: 5 years
We will investigate immunodeficiency incidence in patients with severe EBV infection.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2023.
- Background: PubMed 27748521Worth AJ, Houldcroft CJ, Booth C. Severe Epstein-Barr virus infection in primary immunodeficiency and the normal host. Br J Haematol. 2016 Nov;175(4):559-576. doi: 10.1111/bjh.14339. Epub 2016 Oct 17.
- Background: PubMed 27931829Shabani M, Nichols KE, Rezaei N. Primary immunodeficiencies associated with EBV-Induced lymphoproliferative disorders. Crit Rev Oncol Hematol. 2016 Dec;108:109-127. doi: 10.1016/j.critrevonc.2016.10.014. Epub 2016 Nov 2.
- Background: PubMed 26415106Palendira U, Rickinson AB. Primary immunodeficiencies and the control of Epstein-Barr virus infection. Ann N Y Acad Sci. 2015 Nov;1356:22-44. doi: 10.1111/nyas.12937. Epub 2015 Sep 28.
- Background: PubMed 25706097Taylor GS, Long HM, Brooks JM, Rickinson AB, Hislop AD. The immunology of Epstein-Barr virus-induced disease. Annu Rev Immunol. 2015;33:787-821. doi: 10.1146/annurev-immunol-032414-112326. Epub 2015 Feb 11.
- Background: PubMed 24528553Fujiwara S, Kimura H, Imadome K, Arai A, Kodama E, Morio T, Shimizu N, Wakiguchi H. Current research on chronic active Epstein-Barr virus infection in Japan. Pediatr Int. 2014 Apr;56(2):159-66. doi: 10.1111/ped.12314.
- Background: PubMed 21415952Eligio P, Delia R, Valeria G. EBV Chronic Infections. Mediterr J Hematol Infect Dis. 2010 Aug 10;2(1):e2010022. doi: 10.4084/MJHID.2010.022.
- Individual participant dataSharing planned: No
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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.
Jinqiao Sun, Ph.D.,M.D principal investigator
Children's Hospital of Fudan University
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 Infections and Immunodeficiency, run by Children's Hospital of Fudan University at 1 site in China.
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 1 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: finished, as of the sponsor's last update on 9 Feb 2023. 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 China. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Immunodeficiency incidence in patients with severe EBV infection (time frame: 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 NCT03374566, which also lists 6 linked publications.
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 9 Feb 2023.