Determining Risk in Latent Tuberculosis
|ClinicalTrials.gov Identifier: NCT01571739|
Recruitment Status : Terminated
First Posted : April 5, 2012
Last Update Posted : March 15, 2018
- 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.
- To test possible methods of determining a person s risk for developing active TB.
- 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.
- 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 or disease|
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.
|Study Type :||Observational|
|Estimated Enrollment :||1200 participants|
|Official Title:||Risk Stratification in Latent Tuberculosis: PET/CT Findings in TB Contacts|
|Study Start Date :||January 2, 2012|
|Estimated Study Completion Date :||May 20, 2014|
- To estimate the rate of PET plus CXR at baseline among all study participants.
- 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).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01571739
|Korea, Republic of|
|National Medical Center|
|Seoul, Korea, Republic of|
|Principal Investigator:||Clifton E Barry, Ph.D.||National Institute of Allergy and Infectious Diseases (NIAID)|