Genetic Studies of Chronic Active Epstein-Barr Disease

April 20, 2024 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

Genetic Studies of Chronic Active Epstein-Barr Virus Infection

Epstein-Barr virus (EBV) is a member of the human herpes virus family that infects more than 95 percent of the U.S. population. Most infections occur in childhood and cause no symptoms; in adolescents and adults, EBV often causes infectious mononucleosis. It has also been associated with certain forms of cancer. Chronic Epstein-Barr virus (CAEBV) is a rare disease, primarily of children and young adults, that leads to life-threatening infections.

This study seeks to identify genetic mutations responsible for CAEBV. A secondary goal is to learn more about the natural history of CAEBV.

The study will examine blood and tissue samples from up to 50 patients (age 3 and above) with CAEBV and up to 150 of their relatives (age 1 and above). Autopsy samples may be included in the study. Up to 300 anonymous blood samples from the NIH Clinical Center Blood Transfusion Medicine will also be examined for comparison.

No more than 450 milligrams (30 tablespoons) of blood per 8 weeks will be drawn from adult patients, and no more than 7 milliliters per kilogram of blood per 8 weeks will be drawn from patients under age 18. Local health care providers will refer patients to the study and will obtain the samples. Some patients may also be seen at the NIH Clinical Center. Those patients will have a full medical history and physical examination, along with chest X-ray, blood counts, blood chemistry, EBV serologies, and viral load. Other tests, such as CT scan or MRI, may be performed if medically indicated. Patients will be asked to undergo leukapheresis.

In vitro tests on the blood or tissue samples will include analysis for proteins or genes that are involved in the immune response; cloning of portions of patient DNA; transformation of B cells with EBV; measurement of the ability of patient blood cells to kill EBV-infected cells; determination of lymphocyte subsets; and determination of antibodies to EBV or other herpes viruses.

If a genetic cause for CAEBV is found, the investigators will be available to discuss the results with patients in person or by telephone. Genetic indications of risk for other diseases will also be discussed with patients.

Study Overview

Status

Recruiting

Conditions

Detailed Description

Patients with chronic active Epstein-Barr virus (CAEBV) have (a) an illness that began as a primary infection with EBV or markedly elevated titers of antibodies to EBV, (b) histological evidence of organ disease, and (c) elevated EBV DNA levels in the blood or EBV DNA or proteins in affected tissues. This is primarily a disease of children and young adults. Many of these patients develop hypogammaglobulinemia or pancytopenia and death is frequently due to opportunistic infections or B or T cell lymphoproliferative disease. The primary goal of this study is to identify genetic mutations responsible for CAEBV. The secondary goal of this study is to learn more about the natural history of CAEBV. Blood samples or available tissues (e.g. previous biopsy or autopsy material) from patients with CAEBV and their relatives will be analyzed to identify disease genes that are mutated in this population. In addition, some of the patients will be invited to come for evaluation at the NIH Clinical Center. At that time medically indicated studies of disease progression will be performed. Serial virologic and immunologic studies will be performed. Eligible relatives of patients will be studied to compare the gene(s) associated with CAEBV in patients with the gene(s) in their relatives. Knowledge gained from this study has the potential of providing insights into the immunologic control of EBV infections. In addition, identification of the molecular mechanisms for CAEBV may provide insights leading to improved treatments for this disease.

Study Type

Observational

Enrollment (Estimated)

300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • Recruiting
        • National Institutes of Health Clinical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with known or suspected CAEBV and their relatives will be recruited by referrals from health care providers or self-referrals.@@@@@@

Description

  • ELIGIBILITY CRITERIA

CAEBV PATIENTS

Study size: up to 150 patients

Sex distribution: male and female

Age range: 1 year old and above

Patients with known or suspected CAEBV and their relatives will be recruited by referrals from health care providers. The rarity of this disease will markedly limit the number of patients available to study; therefore, we will enroll patients who are 1 year of age and older. However, children under the age of 3 years old will be enrolled as samples- only participants and not be evaluated at the Clinical Center.

Patient recruitment is irrespective of racial and ethnic group or gender. NIAID investigators will be available to answer questions and discuss general aspects of CAEBV and identified genes or modifier genes with participants or their providers.

Eligibility criteria: To be considered having CAEBV, a patient must have:

  1. a severe progressive illness that began as a primary EBV infection, or associated with postive EBV-specific antibody titers (IgG-VCA, ; EA or EBNA) not otherwise explained AND
  2. evidence of major organ involvement such as lymphadenitis, hemophagocytosis, meningoencephalitis, persistent hepatitis, splenomegaly, interstitial pneumonitis, bone marrow hypoplasia, uveitis AND
  3. detection of elevated levels of EBV DNA, RNA or proteins in affected tissues OR elevated levels of EBV DNA in the peripheral blood

Exclusion Criteria:

(a) Any other condition that, in the opinion of the investigator, would make the patient unsuitable for enrollment or could interfere with the patient participating in the study.

RELATIVES OF CAEBV PATIENTS:

Study size: up to 150 relatives of CAEBV patients

Age range: 3 years and above

To determine the genetic basis for this syndrome, the evaluation of blood, saliva and/or previously obtained tissue specimens from healthy relatives of CAEBV patients will serve as controls. No tissue biopsies will be performed on healthy relatives. We will

perform some of the studies listed on samples from normal relatives.

UNRELATED VOLUNTEERS

Study size: up to 300 persons

Age range: 18 years and above

Panels of anonymous blood samples will be obtained through NIH Clinical Center Blood Transfusion Medicine to determine if identified genetic changes are mutations or polymorphisms.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Family-Based
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
CAEBV
Patients with chronic active Epstein-Barr virus.
Hydroa vaccineforme
Patients with EBV hydro vaccineforme.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The primary goal of this study is to identify genetic mutations responsible for CAEBV.
Time Frame: ongoing
Provide insights into the immunologic control of EBV infections.
ongoing

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The secondary goal of this study is to learn more about the natural history of CAEBV, to assess the viral burden and localization, and to determine if defects are present in pathways involved in cytotoxic functions of T or NK cells.
Time Frame: ongoing
Identification of the molecular mechanisms fro CAEBV.
ongoing

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Principal Investigator: Jeffrey I Cohen, M.D., National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 16, 2002

Study Registration Dates

First Submitted

March 22, 2002

First Submitted That Met QC Criteria

March 22, 2002

First Posted (Estimated)

March 25, 2002

Study Record Updates

Last Update Posted (Actual)

April 23, 2024

Last Update Submitted That Met QC Criteria

April 20, 2024

Last Verified

April 17, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 020147
  • 02-I-0147

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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