Sponsor - U.S. Centers for Disease Control & Prevention - Tuberculosis Trials Consortium (TBTC - 200-2009-32598) and U.S. National Institutes of Health (TBRU Contract)
Principal Investigator - John L. Johnson, M.D., CWRU
|Type of Study||Phase 2 clinical trials of TB treatment with pharmacokinetic and surrogate biomarker substudies|
|Design||A pilot study to evaluate nucleic acid amplification and other tests to compare growth characteristics of different solid media during tuberculosis treatment and evaluation of surrogate biomarkers|
|Sample Size||50 subjects|
|Population||HIV-infected and HIV-uninfected adults with initial episodes of newly diagnosed smear-positive, pulmonary TB|
|Study Period||December 2008-March 2010|
|Interactions with TBRU||In 2008, TBTC and TBRU investigators joined together on TBTC Study NAA2M, a collaborative, co-funded study by CDC-TBTC and NIH-TBRU.|
Goal of Study:
This study evaluates routine microbiological and novel molecular markers of patient response to TB treatment, including several types of nucleic acid amplification (NAA) tests. Differences in colony counts on 3 different solid media during standard TB treatment and to obtain sputum, urine and serum samples at defined time intervals are investigated to identify several promising surrogate biomarkers of response to TB treatment.
Microbiology findings from prior TBTC Study 28 and previous studies show a need to better understand the comparative characteristics of mycobacterial growth on several different media. Prior TBTC study 28 required each sputum specimen to be inoculated on both a solid and a liquid medium. MGIT is becoming the international standard for liquid media in clinical practice and in TBTC studies, but different sites use different solid media. Almost all specimens in Study 28 that were culture negative on MGIT were also negative on all solid media, but among patients with positive culture results on MGIT the concordances with solid media varied. The differences in concordance were very small on baseline specimens but increased with time on therapy, until most cultures were negative at 3 months, suggesting that partially treated mycobacterial populations are detected differently by different media. Some of the variation may be due to variations in laboratory practices such as decontamination procedures and inoculum size, but important differences between media are likely.
Previous studies have compared different solid media for diagnosis of TB but no literature is available comparing solid media for specimens from partly treated patients. Understanding the comparative characteristics of different media in detection of mycobacteria from specimens treated with standard techniques in a single laboratory may help to explain differences in response to treatment found between different sites and different studies that use the different media. Quantifying these differences may also help to develop approaches to understanding differences between mycobacterial populations.
Objectives of Study:
- Compare performance of three solid media, LJ, 7H11, and 7H10, for detection of MTB within a single laboratory.
- Compare serial CFUs in solid media with time to detection in MGIT in order to help determine how well time to detection correlates with quantitative cultures.
- Evaluate CD4+ and CD8+ T cell changes as a surrogate marker of response to treatment.
- Evaluate sputum and urine for changes in the presence of mycobacterial DNA, protein, sugars and glycolipids by mass spectrophotometery and other molecular detection devices as potential markers of response to treatment.