NexGen EBA Radiologic and Immunologic Biomarkers of Sterilizing Drug Activity in Tuberculosis

Summary

Background: \- Tuberculosis (TB) is a lung infection caused by bacteria. When people with TB cough, they may spread these bacteria. Researchers are looking for new TB medicines. They want to find a faster way to tell if a drug might combat TB. Objective: \- To learn the effect of different anti-TB drugs on microbiological, radiographic and immunologic markers in people with TB. Eligibility: \- Adults age 18-65 who weigh 30-90 kg and have common TB bacteria that can be treated with common TB medicines. Design: * Participants will be admitted to the hospital for screening. They will have medical history, physical exam, and chest radiograph. They will give blood, urine, and sputum samples. * Participants will be put in 1 of 8 groups. * Participants will get one or a combination of TB medicines daily for about 14 days. * Each day, participants: * Will discuss side effects. * May have a physical exam. * Will spit mucus into a cup. They may breathe in saline water through a nebulizer to make them cough. * Participants will have blood taken 3-4 times during the study * Participants will have 2-3 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) scans. FDG is a radioactive sugar molecule which helps measure TB disease in the lungs. It will be injected into a vein. Participants will lie in a scanner that takes pictures. * Around study day 14, participants will leave the hospital. They will be referred to a local TB clinic. There they will get the standard 4 TB medicines. Those in group 8 will already be on these medicines and will have another FDG-PET/CT on day 28. * Participants will be in the study for up to 28 days.

Timeline

Start

2015-02-25

Primary completion

2017-09-01

Completion

2017-11-14

Publications

• Background Dartois V, Barry CE. Clinical pharmacology and lesion penetrating properties of second- and third-line antituberculous agents used in the management of multidrug-resistant (MDR) and extensively-drug resistant (XDR) tuberculosis. Curr Clin Pharmacol. 2010 May;5(2):96-114. doi: 10.2174/157488410791110797.
• Background Goo JM, Im JG, Do KH, Yeo JS, Seo JB, Kim HY, Chung JK. Pulmonary tuberculoma evaluated by means of FDG PET: findings in 10 cases. Radiology. 2000 Jul;216(1):117-21. doi: 10.1148/radiology.216.1.r00jl19117.
• Background Jindani A, Dore CJ, Mitchison DA. Bactericidal and sterilizing activities of antituberculosis drugs during the first 14 days. Am J Respir Crit Care Med. 2003 May 15;167(10):1348-54. doi: 10.1164/rccm.200210-1125OC. Epub 2003 Jan 6.
• Jones A, Saini J, Kriel B, Via LE, Cai Y, Allies D, Hanna D, Hermann D, Loxton AG, Walzl G, Diacon AH, Romero K, Higashiyama R, Liu Y, Berg A. Sputum lipoarabinomannan (LAM) as a biomarker to determine sputum mycobacterial load: exploratory and model-based analyses of integrated data from four cohorts. BMC Infect Dis. 2022 Apr 2;22(1):327. doi: 10.1186/s12879-022-07308-3.

Drugs

Indications