Training Protocol on the Natural History of Tuberculosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National Institutes of Health Clinical Center (CC)
Information provided by:
National Institutes of Health Clinical Center (CC) Identifier:
First received: September 29, 2010
Last updated: September 26, 2014
Last verified: April 2014


- Tuberculosis (TB) is an infectious disease that affects numerous people worldwide. However, most clinical studies of individuals with TB take place at international sites because there are many fewer cases of TB in the United States than elsewhere in the world. To provide better training for infectious disease staff members at the National Institutes of Health Clinical Center in Washington, D.C., researchers are interested in actively recruiting individuals with TB for research and treatment studies.


  • To provide staff at the National Institutes of Health Clinical Center with increased experience in hands-on treatment of individuals with tuberculosis, including drug-sensitive or drug-resistant forms of the disease.
  • To collect blood and other samples to study the natural history of tuberculosis.


- Individuals 2 years of age and older who have either active or latent tuberculosis.


  • Latent TB patients: Participants will have a single study visit with a physical examination and medical history, and will provide blood samples for testing.
  • Active TB patients: Participants will have an initial visit with a physical examination and medical history, and will provide blood samples for testing. Participants will also provide sputum samples if required, and may have an optional skin punch biopsy to collect a sample of skin tissue for study.
  • Treatment for active TB will be provided as part of this protocol.
  • Active TB participants will return for study visits every 2 months while receiving treatment, and will return every 6 months for 1 year after the end of treatment. Participants may be asked to return more often if researchers determine that additional care is needed to treat the infection.


Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Training Protocol on the Natural History of Tuberculosis

Resource links provided by NLM:

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

Primary Outcome Measures:
  • Develop on-site NIH Clinical Center (CC)/NIAID experience in the standard of care of tuberculosis patients with drug sensitive and drug resistant disease, as well as latent tuberculosis. [ Time Frame: ongoing ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Characterize in vitro immune responses of patients with tuberculosis to a panel of agonists including but not limited to, strains of Mycobacterium tuberculosis (MTB), MTB antigens, and purified stimuli (e.g. Pam3Cys, LPS, HKLM). [ Time Frame: ongoing ] [ Designated as safety issue: No ]
  • Characterize lymphoid profiles of patients with drug-sensitive (DS) TB, multi-drug resistant (MDR) TB, and extensively drug-resistant (XDR) TB both during acute, convalescent, and cured disease. [ Time Frame: ongoing ] [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: August 2010
Detailed Description:

Mycobacterium tuberculosis is a slow-growing bacterium that establishes latent infection in millions of persons worldwide, but only leads to disease in 10% or less of these individuals. It typically causes pneumonia, however dissemination to almost any other organ is possible. Drug resistance of the organism, co-infection with HIV, and paradoxical reactions upon treatment are all factors that may complicate treatment.

Host defense against mycobacterial infections is important. Specific defects within the innate immune system lead to Mendelian susceptibility to mycobacterial infections. Human immunodeficiency virus (HIV) infected individuals and persons treated with anti-tumor necrosis factor antibodies are highly susceptible to tuberculosis infection. Genetic influence on susceptibility to TB disease is complex and does not seem to be confined to a single gene or pathway.

Advancement in molecular techniques has expanded our understanding of the pathogenesis and epidemiology of M. tuberculosis. Identification of gene mutations that confer antibiotic resistance are being exploited as alternatives to conventional drug susceptibility testing.

The natural history of all forms of TB disease (including co-infection with HIV and other infections) will be followed, and M. tuberculosis isolates and blood from 100 infected patients will be obtained in order to study organism virulence and host immune function and genetic/epigenetic factors. While it is recognized that the number of tuberculosis cases that occur in the Washington, DC area and nationally is low, it is imperative that a mechanism is in place to evaluate and treat these patients at the NIH Clinical Center. This protocol will allow NIH infectious diseases trainees to manage challenging cases of tuberculosis.


Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

For All Patients

Patients may be included in this study who:

  • Have a type of TB disease which, in the opinion of the Principal Investigator (PI), will assist in meeting the Primary Objective of this study (i.e., Develop experience in the standard of care of tuberculosis patients ).
  • Are aged 2 years or older.
  • Have a primary care physician, infectious diseases physician, pulmonologist, or tuberculosis specialist outside of the NIH who can provide care of his or her TB infection outside the NIH, provide directly observed therapy (DOT) if necessary, and monitor for side effects and toxicity of TB medications.
  • Are willing to consent to storage of specimens for future research.
  • Subjects enrolled will be able to provide informed consent for themselves, or if they lack the capacity to provide informed consent, the study team will comply with MAS M87.4, if the Principal Investigator believes there is the prospect of direct benefit for the patient.

For Patients with Latent TB

In addition to the above described inclusion criteria for all patients, patients may be included in the Latent TB part of this protocol who:

- Have documented evidence of a positive PPD skin test or Interferon Gamma Release Assays (IGRA) test meeting American Thoracic Society (ATS)/CDC guidelines for latent TB (Appendix B); conversion can have occurred at any time.

For Patients with Active TB

In addition to the above described inclusion criteria for all patients, patients may be included in the Active TB part of this protocol who:

  • Have active tuberculosis of any drug susceptibility pattern and any site of infection as determined by smear, culture, or biopsy.
  • Have appropriately documented clinically suspicious active tuberculosis without definitive microbiology confirmation.


Patients will be excluded from this study who:

  • Are incarcerated.
  • Have been ordered by a court to take TB medications.
  • Are unwilling or unable to comply with prescribed therapy.
  • Subjects that lack the capacity to provide informed consent autonomously are excluded; unless there is an appropriate legal guardian, Durable Power of Attorney (DPA) or surrogate who is willing to provide consent. A Bioethics consult will make this determination, based on an assessment of the patient and potential surrogate, in accordance with policy MAS M87-4.
  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 identifier: NCT01212003

Contact: Pamela A Welch, R.N. (301) 402-0449
Contact: Steven M Holland, M.D. (301) 402-7684

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   
Sponsors and Collaborators
Principal Investigator: Steven M Holland, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Additional Information:
Publications: Identifier: NCT01212003     History of Changes
Other Study ID Numbers: 100195, 10-I-0195
Study First Received: September 29, 2010
Last Updated: September 26, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Mycobacterium Tuberculosis
Active Tuberculosis
Latent Tuberculosis

Additional relevant MeSH terms:
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Mycobacterium Infections processed this record on October 20, 2014