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Trial record 1 of 1 for:    NCT01011712
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The Natural History of Severe Viral Infections and Characterization of Immune Defects in Patients Without Known Immunocompromise

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 11, 2016 by National Institutes of Health Clinical Center (CC)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ) Identifier:
First received: November 10, 2009
Last updated: April 21, 2017
Last verified: August 11, 2016

November 10, 2009
April 21, 2017
October 27, 2009
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In this study, we will evaluate patients without known or not fully characterized immunodeficiency who have a history of or present with severe, persistent, or treatment-refractory viral infections. Herpesvirus, adenovirus, human papillomavirus ... [ Time Frame: 5 years ]
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Complete list of historical versions of study NCT01011712 on Archive Site
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The Natural History of Severe Viral Infections and Characterization of Immune Defects in Patients Without Known Immunocompromise
The Natural History of Severe Viral Infections and Characterization of Immune Defects


  • Infections caused by viruses are common causes of illnesses: the common cold, many ear infections, sore throats, chicken pox, and the flu are caused by different viruses. Usually, these illnesses last only few days or, at most, a few weeks. Some virus infections like influenza are cleared from the body, and others such as the chicken pox virus remain in the body in an inactive state. However, some people may become quite ill when they are infected with a particular virus, possibly because part of their immune system does not respond properly to fight the virus.
  • Researchers have discovered some reasons why a person may not be able to clear an infection caused by a virus. Some persons have changes in the genes that involve the immune system that result in the inability to properly control infection with a particular virus. Identifying changes in genes that involve the immune system should help scientists better understand how the immune system works to protect people from infection and may help develop new therapies.


  • To study possible immune defects that may be linked to a particular severe viral infection.
  • To determine if identified immune defects are genetic in origin.


  • Individuals of any age who have or have had a diagnosis of a virus infection that physicians consider to be unusually severe, prolonged, or difficult to treat.
  • Relatives of the participants with a severe viral infection may also participate in the study. We will use their blood and/or skin specimens to try to determine if identified immune defects are hereditary.


  • Prior to the study, the participant's doctor will give researchers the details of the infection, along with medical records for review. Eligible participants will be invited to the NIH Clinical Center for a full evaluation as an outpatient or inpatient.
  • At the Clinical Center, participants will be treated with the best available therapy for the particular viral infection, and researchers will monitor how the infection responds to the treatment.
  • Researchers will take intermittent blood samples and conduct other tests (such as skin biopsies) to evaluate the immune system. - During and after the illness, researchers will conduct follow-up visits to determine the course of infection and response to therapy.

Viral infections in the normal host are usually self-limited as the innate and acquired immune systems mount successful antiviral responses. However, in some instances, apparently immunocompetent persons manifest infections with viruses that would otherwise be observed only in severely immunocompromised hosts. For example, cases of herpes simplex virus (HSV) encephalitis, esophagitis orgastritis, cytomegalovirus (CMV) colitis, adenovirus hepatitis or pneumonitis, recurrent or persistent skin infections caused by HSV or varicella zoster virus (VZV), severe warts caused by human papillomavirus (HPV), recurrent respiratory papillomatosis caused by HPV, severe influenza or respiratory syncytial virus pneumonia, and progressive multifocal leukoencephalopathy (PML) due to JC polyomavirus have been described in apparently immunocompetent patients. While a variety of case reports have described severe viral infections in immunocompetent hosts, the pathogenesis of the vast majority of these cases is not understood, and therapy can be unsuccessful.

In this protocol, we will evaluate patients without known immunocompromise, who have severe, persistent, or treatment-refractory viral infections caused by herpesviruses, adenoviruses, polyoma viruses, papillomaviruses, or other viral infections. We will investigate whether certain host or virologic factors predispose these individuals to severe disease. We will also determine the usefulness of various microbiologic tests (e.g., cultures, serology, molecular assays) for following the course of infection in these patients. The physicians in the Clinical Center will provide optimal therapy for these patients, as part of standard of care. Identification of virologic or host factors that predispose these patients to severe viral infections may have important implications for elucidating the pathogenesis of infection and for the development of novel therapies.

Observational Model: Case-Only
Time Perspective: Prospective
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  • EBV
  • HSV
  • VZV
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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Participants must meet all the following inclusion criteria in order to participate in this study:

  1. Children or adults (regardless of age) without a known or fully defined immunodeficiency and with a definitively diagnosed severe viral infection, including infection caused by herpesviruses (HSV-1, HSV-2, CMV, EBV, VZV, HHV-6, HHV-7, HHV-8), human papillomavirus (e.g., severe recalcitrant warts), adenovirus, polyomavirus (such as JC virus and BK virus), or influenza virus. Viral infections that would be considered "opportunistic-like", such as herpesvirus esophagitis, herpesvirus encephalitis, CMV colitis, or progressive multifocal leukoencephalopathy (caused by the JC polyoma virus), will be of particular interest in this protocol.


    Children or adults with a well-documented prior, severe, persistent, or treatment refractory viral infection(s), who have clinically recovered from the viral infection within the past year. If such a patient is not able to visit the NIH for evaluation, his or her personal physician may mail-in blood or other clinical specimens to the NIH for analysis of possible immune defects and for analysis of the virus for mutations, if indicated.

  2. Ongoing care by a referring physician.
  3. Willingness to allow storage of blood and tissue samples for future analyses.


Relatives (2 years or above) may be recruited to establish the genetic origin of immune defects that may be identified in the study subjects. We may obtain blood, buccal swabs or a skin biopsy from the relatives.

  1. Males and females will be accepted.
  2. Adult relatives or the guardians of minor relatives must be willing and capable of providing informed consent after review of protocol procedures that are described in the consent form, with an appropriate study team member.
  3. Participating relatives agree to have blood stored for future studies of the immune system.


Participants meeting any of the following exclusion criteria at baseline will be excluded from study participation:

  1. Patients with previously diagnosed conditions associated with immunodeficiency (e.g., a history of HIV infection or a positive test for HIV) or patients with conditions requiring either daily systemic corticosteroids exceeding a dose equivalent to10 mg/day of prednisone or other significant immunosuppressant therapy (e.g., organ or stem cell transplant recipients).

    Note: Patients will be included if treatment with steroids or other immunosuppressive medication was begun to reduce disease associated with the infection and instituted AFTER the viral disease began.

  2. Women who are pregnant.
  3. Any condition or major comorbidity that the study investigators believe will compromise the patient's ability to comply with the requirements of the study.
Sexes Eligible for Study: All
2 Years to 100 Years   (Child, Adult, Senior)
Contact: Doreen L Garabedian, R.N. (301) 594-3094
Contact: Lesia K Dropulic, M.D. (301) 496-7675
United States
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National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
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Principal Investigator: Lesia K Dropulic, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health Clinical Center (CC)
August 11, 2016

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