Evaluation and Follow-up of Patients With Cryptococcosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00001352
First received: November 3, 1999
Last updated: March 14, 2014
Last verified: December 2013
  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
Lymphopenia

Study Type: Observational
Official Title: Genetic Susceptibility to Cryptococcal and Other Systemic Fungal Infections in Adults

Resource links provided by NLM:


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

Estimated Enrollment: 500
Study Start Date: March 1993
Detailed Description:

Cryptococcosis is a fungus which causes infection in immunocompromised patients, such as those with the acquired immunodeficiency syndrome, but also in occasional persons who have been previously healthy. The reasons for infection of ostensibly normal persons remain unclear. Now that enumeration of lymphocyte subpopulations has become more common, a low number of DC4 cells have been found in some cryptococcosis patients. These patients fit the CDC definition of idiopathic CD4 Lymphocytopenia (ICL) in that they have CD4 levels below 300/microl, no laboratory evidence of HIV infection and no defined immunodeficiency or therapy associated with depressed CD4 levels. One of the first five cases of ICL reported in that issue of MMWR was presented with cryptococcal meningitis. According to Dr. Harold Jaffe at CDC, about one fourth of the ICL cases reported to CDC by December, 1992 have presented with cryptococcosis (personal communication.) However the incidence of ICL in cryptococcosis patients is unknown. Also, the long term outcome of patients with cryptococcosis and ICL patients is unclear. For example, it is not known if they are more difficult to cure than other previously normal patients, as would be the case had they been HIV seropositive.

In addition, novel discovery methods such as genome wide association studies (GWAS) of copy number variation (CNV) and single nuclear polymorphisms (SNP s) have been used to identify genes involved in patient diseases. We would thus like to supplement the methods previously used in this protocol with genetic comparisons, maintaining the original objectives of the study.

This protocol will bring to NIH patients with cryptococcosis who have no underlying disease, either with or without prior treatment of their mycosis. Those who have ICL will be compared with those not having ICL for response to treatment, prior and future opportunistic infections other than cryptococcosis, and future course of the lymphocyte subpopulations.

  Eligibility

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

    1. Positive culture of Cryptococcus neoformans from any body site;
    2. First degree relative (mother, father, sister, brother) of patients with positive Cryptococcus neoformans from anybody site.
    3. Age 18 years or older; and
    4. Ability to provide informed consent.

EXCLUSION CRITERIA (Apply to patients only):

  1. Known HIV positive serology or other condition predisposing to cryptococcosis, including but not limited to corticosteroid therapy equivalent to prednisone 20 mg per day or more or acidosis.
  2. Dementia impairing informed consent.

INCLUSION CRITERIA FOR CONTROLS:

  1. History of ICL without a history of cryptococcosis or
  2. Other conditions which may predispose to cryptococcosis, such as other opportunistic infections and autoimmune diseases.

EXCLUSION CRITERIA FOR CONTROLS:

  1. Iatrogenic immunodeficiency such as concomitant corticosteroid treatment (greater than an equivalent of 10 mg of prednisone daily for more than 2 weeks), other immunosuppressive medications, total body irradiation or others
  2. Dementia impairing informed consent.

INCLUSION CRITERIA FOR HEALTHY VOLUNTEERS:

  1. Weight greater than 110 lbs
  2. Hemoglobin level greater than 11 g/dl
  3. Ages 18-70

EXCLUSION CRITERIA FOR HEALTHY VOLUNTEERS:

  1. History of hepatitis B or hepatitis C
  2. HIV positivity
  3. Any condition which in the opinion of the investigators may alter immune function
  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: John E Bennett, M.D. (301) 402-0198 jbennett@niaid.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: John E Bennett, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00001352     History of Changes
Other Study ID Numbers: 930106, 93-I-0106
Study First Received: November 3, 1999
Last Updated: March 14, 2014
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
Lymphopenia
Mycoses
Leukopenia
Leukocyte Disorders
Hematologic Diseases
Immunologic Deficiency Syndromes
Immune System Diseases

ClinicalTrials.gov processed this record on July 28, 2014