Chronic Active Epstein-Barr Virus Clinical Trial
Official title:
Genetic Studies of Chronic Active Epstein-Barr Virus Infection
| NCT number | NCT00032513 |
| Other study ID # | 020147 |
| Secondary ID | 02-I-0147 |
| Status | Recruiting |
| Phase | |
| First received | |
| Last updated | |
| Start date | April 16, 2002 |
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.
| Status | Recruiting |
| Enrollment | 300 |
| Est. completion date | |
| Est. primary completion date | |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 1 Year to 120 Years |
| Eligibility | - 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. |
| Country | Name | City | State |
|---|---|---|---|
| United States | National Institutes of Health Clinical Center | Bethesda | Maryland |
| Lead Sponsor | Collaborator |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) |
United States,
Cohen JI, Jaffe ES, Dale JK, Pittaluga S, Heslop HE, Rooney CM, Gottschalk S, Bollard CM, Rao VK, Marques A, Burbelo PD, Turk SP, Fulton R, Wayne AS, Little RF, Cairo MS, El-Mallawany NK, Fowler D, Sportes C, Bishop MR, Wilson W, Straus SE. Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States. Blood. 2011 Jun 2;117(22):5835-49. doi: 10.1182/blood-2010-11-316745. Epub 2011 Mar 31. — View Citation
Cohen JI. Optimal treatment for chronic active Epstein-Barr virus disease. Pediatr Transplant. 2009 Jun;13(4):393-6. doi: 10.1111/j.1399-3046.2008.01095.x. No abstract available. — View Citation
Okamura T, Hatsukawa Y, Arai H, Inoue M, Kawa K. Blood stem-cell transplantation for chronic active Epstein-Barr virus with lymphoproliferation. Lancet. 2000 Jul 15;356(9225):223-4. doi: 10.1016/S0140-6736(00)02488-0. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | The primary goal of this study is to identify genetic mutations responsible for CAEBV. | Provide insights into the immunologic control of EBV infections. | ongoing | |
| Secondary | 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. | Identification of the molecular mechanisms fro CAEBV. | ongoing |