Active clinical trials for "Tuberculosis"

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.

Assess the Efficacy of HUEXC030 as Add-on Excipient to Eradicate Anti-Tuberculosis Drugs Induced Hepatic Injury ( ATDH ) in Subjects with Pulmonary Tuberculosis

The investigators will determine the bactericidal activity of high-dose isoniazid against M. tuberculosis isolates that are (1) susceptible to isoniazid at 2.0 mcg/ml but resistant at 0.1 and 0.4 mcg/ml or (2) susceptible at 0.4 mcg/ml but resistant at 0.1 mcg/ml when tested in the BD MGIT 960 system. Further, the investigators will investigate the molecular genetic determinants of these differences in susceptibility. To achieve these objectives the investigators will carry out an innovative variation on early bactericidal activity (EBA) study methodology. Patients at risk for drug-resistant TB will be screened for INH resistance using approved molecular assays. In those with INH-resistant TB, the investigators will quickly perform phenotypic DSTs using the direct method in the Bactec Mycobacterium Growth Indicator Tube (MGIT) 960 system, so results will be available within 7 days. If the DST results show the susceptibility patterns noted above, patients will receive 900 mg/d INH (600 mg if <45kg), and assess its effect with serial quantitative sputum cultures for 6 days. If the concentration of viable bacteria decreases significantly, the investigators will interpret this to mean the drug is having an effect. If not, the drug is ineffective. After 6 days, the patients will resume treatment according to national guidelines. In case the investigators identify drugs that are effective under these conditions, the investigators will sequence known and putative genes associated with the action of these drugs for the mycobacterial isolates from these patients.

French guidelines currently recommend to initiate a 4-drug containing regimen associating isoniazid (INH or H), rifampicin (RIFor RMP or R), pyrazinamide (PZA or Z) and ethambutol (EMB or E) pending the results of drug susceptibility testing (DST). The rationale behind routine use of EMB is to prevent the emergence of resistance to rifampicin (RMP), in case of primary resistance to INH. Hence, early detection of resistance to INH and RIF using molecular testing in Mycobacterium tuberculosis could allow early adaptation of antituberculosis treatment: i) start with a 3-drug containing regimen (i.e. INH, RIF, and PZA); ii) early enforcement of treatment when resistance is suspected, pending in depth susceptibility testings. the duration of treatment is 6 months or 12 months.

This is a open-label study, 2-treatment, 2-period, single sequence design. Period 1 will examine the pharmacokinetics of TMC207 in the absence of rifapentine or rifampicin. Subjects will receive a single 400-mg dose of TMC207 administered alone on Study Day 1. Period 2 will examine the effects of repeated doses of either rifapentine or rifampicin on TMC207 pharmacokinetics and will begin on Study Day 20. During Period 2, subjects will receive 22 daily doses of either 600 mg rifapentine or rifampicin from Study Day 20 through Study Day 41. A single 400-mg dose of TMC207 will be administered on Study Day 29. Subjects will be confined to the clinic from Study Day-1 to Study Day 2 in the morning of Period 1, and Study Day 19 to Study Day 30 in the morning of Period 2. The study hypothesis is to determine whether Rifapentine affects the pharmacokinetics of TMC207 as measured by effects on Cmax and AUC(0-t) to a lesser degree than rifampicin.

Novel approaches to improve TB treatment outcomes (to reduce morbidity, mortality, and the duration of TB treatment) and to treat XDR-TB cases are urgently required. Host-Directed therapies (especially repurposed drugs such as Non-Steroid AntiInflammatory Drugs NSAIDS) could be useful in this context, and therefore the appropriateness and potential effect of this approach needs to be evaluated in humans. Investigators do propose a prospective, randomized, pilot study to estimate the potential efficacy and safety of using adjunctive ibuprofen for the treatment of XDR tuberculosis.

The purpose of this study is to evaluate the effect of enhanced glycemic monitoring of diabetes upon diabetes glycaemic control during tuberculosis treatment in tuberculosis- diabetes patients.

- Hypothesis: Double dose rifampicin together with earlier monitoring of sputum conversion using vital staining reduces unfavorable outcome of Cat. 1 first-line TB treatment without excess serious toxicity, and allows early switch to specific treatment of MDR-TB without using Cat. 2 retreatment regimen - General study design: This open label, randomised clinical trial is intended as a pilot study on the efficacy and safety of high-dose rifampicin and feasibility and added value of auramine and/or FDA vital staining sputum smear after 2 weeks of intensive treatment phase. If this proof-of-concept study provides substantial indication of benefit without indication of excess toxicity, the data from the study will be used to design a larger scale, cluster-randomized study. The aim of this cluster randomised study would be to provide definite proof of the benefit of the intervention on adverse treatment outcomes and lack of excess toxicity associated with high dose rifampicin. In addition, the cluster-randomized study would provide a more precise assessment of the suppression and prevention of (acquired) resistance endpoints. An interim analysis is thus planned at the time the last recruited patient finishes treatment, i.e. about 9 months after the end of recruitment. It will focus on assessment of drug toxicity versus suggested benefits of the intervention. This analysis will be primarily performed for the go/no-go decision and design considerations for the cluster-randomized trial. The decision on proceeding to the cluster randomized study will be based on the absence of excess toxicity, a trend toward a reduction of unfavourable outcomes (excluding relapse), and possible favourable effects on initially present low-resistance mutations / mutations acquired during treatment. It will also allow to adapt the design of the larger study particularly regarding the algorithm for resistance screening, and whether or not treatment shortening could be justified with rapid initial conversion.

This is a Phase I, single-center, double-blinded, randomized, placebo-controlled, five-period cross-over clinical study of PA-824 to evaluate the effect of PA-824 and of PA-824 plus moxifloxacin on cardiac repolarization (QT/QTc interval duration) in a total of 75 healthy male and female participants, aged 18 to 45 years. Moxifloxacin will be used as an active control. Participants will be blinded to the treatments they will receive. The study consists of a screening period up to 26 days; enrollment, 1 day; five in-patient treatment periods consisting of an admission day (except in the first treatment period, when the pre-dose day is the baseline), dosing day and two post-dosing days; an out-patient period of at least three days and not more than 10 days between treatment periods; and a final visit 7 - 14 days after discharge from the last treatment period.

The purpose of this study is to assess the mycobactericidal activity of the moxifloxacin plus PA-824 plus pyrazinamide regimen after 8 weeks of treatment.