Determining Risk in Latent Tuberculosis

This study has been terminated.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01571739
First received: April 4, 2012
Last updated: May 21, 2014
Last verified: May 2014
  Purpose

Background:

- Tuberculosis (TB) is a leading cause of death worldwide. Those who are exposed to the TB bacteria but have not become sick are said to have latent TB. Many people with latent TB will not get sick from it, but some people will develop active TB and become sick. Much is known about how to treat and diagnose active TB, but little is known about the best way to treat latent TB. Researchers also want to know more about the risk that latent TB will develop into active TB, and whether it is possible to test for this risk.

Objectives:

- To test possible methods of determining a person s risk for developing active TB.

Eligibility:

- Individuals between 20 and 60 years of age who (1) have active TB, (2) were exposed to someone with active TB in the past 9 months, or (3) have not been exposed to TB.

Design:

  • Participants will be separated into groups based on their exposure to TB.
  • Healthy participants who were not exposed to TB will answer questions about their medical history. They will also provide blood and urine samples.
  • Participants who have active TB will have a physical exam and medical history. They will provide blood, urine, and sputum samples, and will have a chest x-ray. They will be treated with the standard of care for active TB. Some participants with active TB may have additional tests as part of this study.
  • Participants who were exposed to TB and have latent TB will have a physical exam and medical history. They will provide blood, urine, and sputum samples, and will have a chest x-ray. They will be asked to return for five more clinic visits over the next 12 months to repeat these tests. They may also have additional chest imaging studies depending on the study needs.
  • Some of the exposed participants may have been exposed to drug-resistant TB. These participants will receive the drug isoniazid to take on a regular schedule to help prevent the latent TB from becoming active TB.

Condition
Latent Tuberculosis

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Risk Stratification in Latent Tuberculosis: PET/CT Findings in TB Contacts

Resource links provided by NLM:


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

Primary Outcome Measures:
  • To estimate the rate of PET plus CXR at baseline among all study participants.

Secondary Outcome Measures:
  • To estimate the rate of PET+/CT- at baseline among all study participants.
  • To estimate the rate of regression of PET plus scans (to normal) at 3 and 12 months among the untreated subjects (n=30).

Estimated Enrollment: 1200
Study Start Date: January 2012
Estimated Study Completion Date: May 2014
Detailed Description:

The efficacy of treating tuberculin skin test (TST) positive, or interferon gamma release assay (IGRA) positive, contacts of tuberculosis (TB) cases to prevent progression to disease is well established. However the length of treatment, and the toxicity associated with the currently used regimens, means that the risk may outweigh the benefit and treatment completion rates are poor. In addition, no proven regimens are available for contacts of multidrug resistant tuberculosis (MDR-TB) cases. Because as few as 2% of contacts develop active TB over 1 year and no surrogate markers are available, drug trials to assess novel treatments typically require thousands of subjects followed up for many years. (18F)-fluoro-2-deoxy-D-glucose positron emission tomography/computer tomography (FDG-PET/CT) may prove a useful surrogate for more targeted chemoprophylaxis as well as a means to rapidly evaluate novel prophylactic regimes in future studies.

Up to 40% of immune-sensitized TB contacts with normal chest radiographs (CXR) have abnormalities on conventional chest CT. FDG-PET/CT not only will allow characterization of the metabolic activity of these lesions but is also likely to reveal significantly increased metabolic activity within regional lymph nodes that may otherwise be anatomically normal. Based on previous studies, we predict that up to 65% of contacts will have combined chest PET/CT abnormalities and that up to 50% of contacts who are treated, will have increased FDG uptake that will resolve with treatment. By contrast, PET screening studies demonstrate abnormal pulmonary FDG uptake occurs in 0.9% of healthy individuals.

The development of biomarkers more predictive of disease progression is also highly desirable, but for similar reasons evaluating them is challenging. This novel approach of using FDG-PET/CT to benchmark the dynamic immunological, transcriptional, or metabolic changes that occur early in tuberculosis infection, we hope will accelerate biomarker discovery. In this study we propose to evaluate these predictions in order to lay the foundation for future studies.

  Eligibility

Ages Eligible for Study:   20 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INDEX CASES:

INCLUSION CRITERIA:

  1. Either confirmed sputum smear positive and culture positive for M. tb within the last 12 months OR sputum smear positive and genotypically confirmed M.tb with culture awaited
  2. Age greater than or equal to 20 years old

20 Smear Positive Pulmonary TB Biomarker Index Case Controls:

INCLUSION CRITERIA:

  1. Genotypically confirmed sputum smear positive pulmonary tuberculosis
  2. Culture awaited or confirmed Mtb
  3. Not commenced anti-tuberculous therapy
  4. Age greater than or equal to 20 years old

EXCLUSION CRITERIA:

  1. Age > 60 years old
  2. Known diagnosis of chronic inflammatory condition (e.g. Sarcoid, RA, connective tissue disorder) or on immunosuppressive medication

WITHDRAWAL CRITERIA:

1) Culture negative for M.tb

QF-GIT Positive Contacts:

INCLUSION CRITERIA:

  1. Contacts of index case
  2. QF-GIT positive
  3. Age greater than or equal to 20 years old
  4. Normal CXR

EXCLUSION CRITERIA:

  1. Exposure to an index case who commenced treatment for a current episode of TB (one that was not successfully treated, per WHO definition) more than 15 months ago
  2. Previously diagnosed or treated TB
  3. Symptoms or signs of active TB
  4. Symptoms or signs of acute illness
  5. CXR suggestive of active tuberculosis or parenchymal abnormalities known or suspected to be caused by alternative pathology
  6. HIV positive or other significant immunocompromise
  7. Age > 60
  8. Smoker > 30 pack years
  9. Previously diagnosed malignancy
  10. Previously diagnosed chronic lung infection (e.g., non tuberculosis mycobacteria [NTM], Fungal, Paragonimus)
  11. Known diagnosis of chronic inflammatory condition associated with pulmonary pathology (e.g., Sarcoidosis, RA, Wegener s granulomatosis, bronchiectasis)
  12. Inhaled or systemic steroid use within previous 2 weeks (subject may return for enrollment 2 weeks after last dose) and need for ongoing steroid therapy
  13. Breast feeding, pregnant, or planning pregnancy
  14. Anticipated poor compliance
  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: NCT01571739

Locations
Korea, Republic of
National Medical Center
Seoul, Korea, Republic of
Sponsors and Collaborators
Investigators
Principal Investigator: Clifton E Barry, Ph.D. National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT01571739     History of Changes
Other Study ID Numbers: 999912036, 12-I-N036
Study First Received: April 4, 2012
Last Updated: May 21, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Biomarker
Latent Tuberculosis
IGRA
Isoniazid
TB Lymphadenopathy
Tuberculosis
TB

Additional relevant MeSH terms:
Tuberculosis
Latent Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on July 23, 2014