Genetic Studies of Chronic Active Epstein-Barr Disease

This study is currently recruiting participants.
Verified June 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00032513
First received: March 22, 2002
Last updated: March 14, 2014
Last verified: June 2013

March 22, 2002
March 14, 2014
March 2002
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Complete list of historical versions of study NCT00032513 on ClinicalTrials.gov Archive Site
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Genetic Studies of Chronic Active Epstein-Barr Disease
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 2 and above) with CAEBV and up to 150 of their relatives (age 2 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.

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.

Observational
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Epstein-Barr Virus Infections
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
300
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  • ELIGIBILITY CRITERIA

CAEBV PATIENTS

Study size: up to 150 patients

Sex distribution: male and female

Age range:no minimum nor maximum age

Patients known to have 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.

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 at least 6 months ago as a primary EBV infection, or associated with markedly elevated EBV-specific antibody titers (IgG-VCA greater than or equal to 1:5,120; EA greater than or equal to 1:640 or EBNA less than 1:2 with other serologies positive) 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 AND

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: 2 years and above

To determine the genetic basis for this syndrome, the evaluation of blood and 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 studies on blood 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.

Both
2 Years and older
Yes
Contact: Siu-Ping Turk, R.N. (301) 451-7661 sturk@cc.nih.gov
Contact: Jeffrey I Cohen, M.D. jcohen@niaid.nih.gov
United States
 
NCT00032513
020147, 02-I-0147
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National Institute of Allergy and Infectious Diseases (NIAID)
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Principal Investigator: Jeffrey I Cohen, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health Clinical Center (CC)
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP