Evaluation and Follow-up of Patients With Cryptococcosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier:
NCT00001352
First received: November 3, 1999
Last updated: February 3, 2015
Last verified: September 2014
  Purpose

This 5-year study will follow the course of disease in previously healthy patients with cryptococcosis who developed the disease for no identifiable reason.

Individuals with a positive culture of Cryptococcus neoformans 18 years of age and older without HIV infection or other condition predisposing to cryptococcosis (such as high-dose corticosteroid therapy, sarcoidosis, or a blood cancer) may be eligible for this study. Candidates who test positive for HIV infection may not participate.

Participants will have a physical examination, medical history, routine blood tests and assessment of disease activity upon entering the study. Patients who may have active cryptococcosis will also have a lumbar puncture (spinal tap) and additional blood tests. Following the initial evaluation, patients receiving treatment for cryptococcosis will come to the NIH Clinical Center as needed to manage their disease, typically no less than every 3 months. Other patients will be seen every 6 to 12 months. The visits will include a medical history, physical examination, and blood and urine tests.


Condition
Cryptococcosis

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Cryptococcosis in Previously Healthy Adults

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Fungal Clearance [ Time Frame: 0, 2 weeks, 1m, 3, 6, and 12 months following the end of amphotericin B induction therapy ] [ Designated as safety issue: No ]
  • Neurologic sequalae [ Time Frame: 0, 2 weeks, 1m, 3, 6, and 12 months following the end of amphotericin B induction therapy ] [ Designated as safety issue: No ]

Estimated Enrollment: 600
Study Start Date: March 1993
Detailed Description:

Cryptococcus is a fungus that causes infections most commonly in immunocompromised patients, such as those with AIDS and solid organ transplant recipients, particularly renal transplant recipients (1-3). However, approximately one-third of cases fall outside these groups and, overall, 12.9-17.9% have no readily identifiable immune defect (4, 5). The genetic factors, which may predispose to cryptococcosis and the immune response in these patients, have not been extensively studied.

This protocol is designed to examine the immune deficits that predispose to cryptococcosis as well as the clinical and immune responses among previously healthy adults. The patients included will have an unknown predisposing condition and cryptococcosis. Patients will undergo blood, saliva, and tissue sampling. Throughout the study, patients will be provided with standard medical care and will be seen as often as necessary to manage their condition. Patients in whom microbiologic control of the infection has occurred but in whom inflammation is causing neurologic damage may be treated with corticosteroids or other immunosuppressive agents. Genetically related family members of patients will also be screened for clinical, in vitro, immune, and genetic correlates of immune abnormalities. Healthy adult volunteers, as a comparison group, will be enrolled as a source of blood samples for research testing. Moreover, with respect to cryptococcosis, patients with isolated non-CNS disease (e.g., pulmonary) may serve as a subset comparator to those with central nervous system (CNS) involvement a major tissue tropism for Cryptococcus.

Genetic and immunologic testing will be performed on all subjects (patients, relatives, and healthy volunteers) to evaluate for possible immunogenetic factors that lead to susceptibility to cryptococcosis. Among the aims of this protocol are to better understand the pathophysiology and genetic factors that lead to defects in host defense and to use modern and evolving methods in molecular and cellular biology to elucidate the pathogenesis of this particular susceptibility. A better understanding of the underlying pathophysiology of immune defects and genetic susceptibility to fungal infections could allow for the rational development of novel therapies for such diseases and to benefit future patients.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

Patients:

Patients must:

  1. Have one of the following as determined by information collected from their medical records, telephone interviews or from a referring physician:

    -cryptococcosis with unknown immune deficiencies (including idiopathic CD4+ lymphopenia ICL)

    • histopathology showing cryptococci; or
    • culture of Cryptococcus neoformans or Cryptococcus gattii
    • a positive cryptococcal antigen in the serum and/or CSF, together with CSF cell count and chemistry consistent with cryptococcal meningitis.
  2. Be over the age of 18 years old.
  3. Have a primary physician outside of the NIH.
  4. Agree to undergo genetic testing that will include WES and high density SNP arrays as appropriate for possible WES linkage studies.
  5. Allow samples to be stored for future research.

Blood Relatives of Patients:

Blood relatives must:

  1. Be a genetic relative of a patient enrolled in this study
  2. Be over the age of 18 years old
  3. Agree to undergo genetic testing that may include WES and high density SNP analysis
  4. Allow samples to be stored for future research

Healthy Volunteers:

Healthy volunteers must:

  1. Be between the ages of 18 and 70 years old
  2. Allow samples to be stored for future research

EXCLUSION CRITERIA:

Patients

Patients will be excluded for any of the following:

  1. The presence of certain types of acquired abnormalities of immunity due to:

    • HIV
    • Cancer chemotherapeutic agent(s)
    • An underlying malignancy could be grounds for possible exclusion of a patient if in the opinion of the investigator, the underlying disease predisposed the patient to the infection
    • Monoclonal antibody therapy directed against a patient s immune system
  2. Any condition which in the opinion of the investigator may interfere with the evaluation of a co-existing abnormality of immunity that is exclude patients with Cushing s disease that have very high cortisol levels at the time of diagnosis of their cryptococcosis.

Blood Relatives of Patients:

Blood relatives will be excluded for the following:

Any condition which in the opinion of the investigator may interfere with evaluation of an immune system abnormality that is the subject of study under this protocol.

Healthy Volunteers:

Healthy Volunteers will be excluded for any of the following:

  1. HIV or viral hepatitis (B or C).
  2. History of recurrent or severe infections.
  3. History of intravenous drug use.
  4. History of engaging in high risk activities for exposure to HIV;
  5. Receiving chemotherapeutic agent(s), immunosuppressants or have underlying malignancy.
  6. Pregnancy.
  7. Have history of heart, lung, kidney disease, or bleeding disorders.
  8. Any condition which in the opinion of the investigator may interfere with evaluation of an immune system abnormality that is the subject of study under this protocol.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001352

Contacts
Contact: Anil A Panackal, M.D. (301) 496-2775 anil.panackal@nih.gov
Contact: Peter R Williamson, M.D. (301) 443-8339 williamsonpr@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Peter R Williamson, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier: NCT00001352     History of Changes
Other Study ID Numbers: 930106, 93-I-0106
Study First Received: November 3, 1999
Last Updated: February 3, 2015
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Cryptococcus Neoformans
Cryptococcosis
CD4

Additional relevant MeSH terms:
Cryptococcosis
Mycoses

ClinicalTrials.gov processed this record on August 27, 2015