Active clinical trials for "Tuberculosis"

The investigators will study the efficacy of a novel cellular phone messaging system to communicate health information and facilitate early return to clinic after abnormal laboratory results in rural Uganda.

The purpose of this study is to compare the efficacy of a 'new treatment regimen including delamanid, linezolid, levofloxacin, and pyrazinamide for nine or twelve months (investigational arm)' and 'the standard treatment regimen including injectables for 20 to 24 months (control arm)' for treating fluoroquinolone-sensitive multidrug-resistant tuberculosis.

Multi-center, prospective study is performed to investigate the efficacy of new short-course regimen for retreatment pulmonary tuberculosis patients. To obtain optimized short-course regimen, decrease treatment cost and improve success rate.

Background: Tuberculosis (TB) is a severe disease and a major cause of death in many people worldwide. It is caused by a bacteria that enters through the lungs and can spread elsewhere in the body. People with latent TB have the bacteria that lie dormant but can become active and cause disease. These people are offered treatment to prevent development of active TB. Worldwide, a lot of people with LTBI also have a parasitic worm called a helminth that can stay in the gut or the blood. These parasites can affect the immune system and cause diseases like TB to become worse. Researchers want to see how helminth infection makes it harder for people to fight TB infection. Objectives: - To study how the immune system of people with latent tuberculosis infection (LTBI) acts to prevent development of active TB. Also, to study how helminth infection might affect this immune response. Eligibility: Adults age 18 70 with LTBI as defined by an approved blood test called QuantiFERON TB Gold. No evidence of infections like Hepatitis or HIV Pregnant subjects and subjects taking medications that suppress the immune system are not eligible. Have not received prior treatment for LTBI. Participants might be still eligible if prior treatment for active TB has been received Design: Screening phase: - Participants will be screened with medical history, physical exam, and blood tests for other infections/conditions which might affect the immune system. They will have testing for active TB i.e. blood testing as well as testing of their spit, scans and X-rays. Baseline phase: Only eligible participants will be entered into the study. Participants will have interviews, medical history, and physical exam. Blood will be drawn from an arm vein for testing. Participants will collect stool samples at home for 3 days in a row to test for helminth infection.. Participants may have apheresis. Blood cells are removed by needle. They pass through a separator machine which returns everything but the cells back to the participant. Participants may have procedures at the start and end of the study that let researchers look into the lungs and collect cells. Study phase, about 2 years: All participants will be offered treatment for LTBI which lasts 6-9 months. Participants being treated for LTBI will have about 11 study visits. They will visit monthly for 9 months while on treatment, then 6 and 12 months after treatment. Participants not eligible/refusing treatment for LTBI will be made aware of active TB, then have 3 other visits, about 6, 12, and 24 months after the baseline visit. Participants who have helminth infection will receive appropriate treatment. All participants will have blood drawn at each visit.

To determine if adjunctive N-acetylcysteine 1200 mg twice a day (BID) accelerates sputum culture conversion and normalization of cellular glutathione in tuberculosis (TB), and to assess its potential effects on lung and immune function

Rationale: Multidrug-resistant tuberculosis (MDR-TB) is defined as tuberculosis resistant to isoniazid and rifampicin. The incidence of MDR-TB worldwide is 3.9% for new cases and 21% for previously treated cases. However, the incidence of previously treated cases can rise to above 50% in eastern European countries. With increasing frequency of MDR-TB (and even extensively drug-resistant types), morbidity and mortality due to TB fail to decline worldwide. Amikacin, one of the drugs against MDR-TB, has the most potent effect when reaching a high peak serum concentration and this means that high doses have to be administered. Treatment with amikacin by inhalation would be a tremendous advantage due to the high local dose in the lungs, obtaining high local levels without the possible toxicity due to high serum levels. With the currently available inhalation techniques these local levels cannot be reached easily. In this protocol, the investigators will perform a pharmacokinetic and local tolerability study of dry powder amikacin using the Cyclops™ in patients with drug susceptible tuberculosis. Objective: primary objective is to investigate the pharmacokinetic properties of dry powder amikacin at different dosages and compare the peak serum values to a single i.v. dose. secondary objective is to assess the local tolerability of dry powder amikacin via the Cyclops™ at different dosages. Study design: single center, active control, ascending dose response study Study population: 8 patients with DSTB. Main study parameters/endpoints: the following pharmacokinetic parameters: actual dose (dose minus remainder in inhaler after inhalation), AUC0-24 (area under the curve from 0-24 h), Cmax (maximum serum concentration), Tmax (time to maximum serum concentration). For the local tolerability the following procedures will be done, drop of FEV1 of >15 % (lung function measurement) and any other reported adverse event are all considered critical to decide on proceeding into a phase 2B (and/or a phase 3) trial. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: All participants included in this study are patients with DSTB, who are admitted at the Tuberculosis Center Beatrixoord. They will receive 3 different doses of amikacin using the DPI with (at least) one week in between doses, they will also receive one dose of intravenous amikacin. Before using the dry powder inhaler (DPI) they will receive instructions and their inspiratory flow will be tested. Before each test dose an indwelling cannula will be inserted and before and after each test dose in total 9 blood samples will be collected. To investigate local tolerability, lung function tests will be performed and the occurrence of adverse events will be scored.

PRACTECAL-PKPD is an exploratory pharmacokinetic and pharmacodynamic sub-study investigating the relationship between the patients' exposure to anti- tuberculosis (TB) drugs in the TB-PRACTECAL trial investigational regimens and their respective treatment outcomes.

The purpose of the study is to compare the efficacy and safety of standard chemotherapy regimen 2HRZE/4HR plus IL-2 and standard regimen 2HRZE/4HR for newly diagnosed smear positive pulmonary tuberculosis.

Utilizing the Crosstalk Among Chicoric Acid, 13-Cis Retinoic Acid(Aerosolized), Minocycline and Vitamin D as a Potent Quadrate Therapy for treating patients with Multidrug-resistant TB and patient with both Multidrug-resistant TB and COVID-19 . A double-edged sword Clinical Study I)Part of Tuberculosis Tuberculosis (TB) is a major infectious disease killer globally. It affected 10 million and killed 1.4 million people in 2019 alone. The predicted impact of the COVID-19 pandemic is an additional 190,000 TB deaths in 2020, and it is expected in the next 5 y that there will be up to a 20% increase in the global TB disease burden , stressing the critical need for new safe and effective drugs against Mycobacterium tuberculosis (Mtb). In addition, controlling multidrug-resistant TB (MDR-TB) presents a huge public health challenge . New drug discovery could require several years with no guarantee but repurposing established may be useful to treat patients with tuberculosis . Here we demonstrate that we could utilize the crosstalk among Chicoric Acid, 13-Cis Retinoic Acid, Minocycline , and vitamin D as a novel quadrate therapy against TB.Drug-resistant tuberculosis represents a global emergency, requiring new drugs. Recently Minocycline was found to be highly potent in laboratory strains of Mycobacterium TB, and 30 drug-sensitive and multidrug/extensively drug-resistant clinical strains were susceptible to clinically attainable dosages. The lung concentration-time profiles of a 7 mg/kg/day human-equivalent minocycline dosage yielded bacterial kill rates comparable to first-line antituberculosis drugs. Extracellular bacilli were destroyed directly by minocycline. Minocycline also killed intracellular bacilli indirectly through granzyme A-driven apoptosis. Furthermore, minocycline showed dose-dependent antiinflammatory effect, suggesting that it may protect tuberculosis patients against immunopathology. A study showed that M. tuberculosis induced the expression of indoleamine 2,3-dioxygenase (IDO), an enzyme involved in tryptophan catabolism, in macrophages and in the lungs of animals (mice and macaque) with active disease. In a macaque model of inhalation TB, suppression of IDO activity reduced bacterial burden, pathology, and clinical signs of TB disease, leading to increased host survival. This increased protection was accompanied by increased lung T cell proliferation, induction of inducible bronchus-associated lymphoid tissue and correlates of bacterial killing . A recent study showed that Minocycline-induced significantly inhibition of IDO expression. But Minocycline-induced inhibition of IDO expression is retinoid-dependent. The combined treatment with minocycline and retinol, however, resulted in a striking, statistically significant decrease in IDO. Co-treatment with minocycline and retinol again resulted in decreased TNF-α and IL-6 levels. A study showed that IL-6 inhibits IFN-γ induced autophagy in Mycobacterium (TB) H37Rv infected macrophages. As well as neutralization of endogenous IL-6 by anti-IL-6 antibody significantly enhances the IFN-γ mediated killing of the intracellular bacteria. Minocycline's anti-inflammatory effects are mediated through RAR signaling. Therefore, The combined treatment with minocycline and retinol is expected to effectively inhibit (TB) and its inflammatory complication, Fortunately, Retinoic Acid significantly inhibits the in vivo growth of M. tuberculosis and the development of tuberculosis. In addition to, 13-Cis RA and Chicoric Acid ( CA ) enhanced the cell surface expression of HLA-DR and CD14 molecules on U937 macrophages and prevented the growth of Mtb within macrophages. Moreover, 13-cis RA and CA, have increased NO generation compared to untreated control macrophages, significantly . Both drugs have a significant inhibitory effect on Mtb growth but CA at the highest concentration was more potent than 13-cis RA . Therefore we will use retinoic acid to induce the effect of Minocycline as well as its ability to inhibit tuberculosis in combination with CA .Recent data showed that Vitamin D support innate immune responses to Mycobacterium TB and Low vitamin D levels were associated with a 5-fold increased risk for progression to tuberculosis. Deficiency of vitamin D has long been implicated in activation of (TB) . Serum vitamin D in TB patients are lower than in healthy controls . Vitamin D has been found to speed up the clearance of (TB) bacteria from the lungs of people with multi-drug resistant TB, according to a study of 1,850 patients. It was showed that Vitamin D receptor (VDR) must form a heterodimer complex with retinoid X receptor (RXR) to regulate gene transcription. Retinol plays a crucial role in lung development and signaling the vitamin D pathway. 9-cis-retinoic acid, an active vitamin A metabolite and the ligand of RXR, assists VDR signaling and suppresses the degradation of circulating vitamin D.

This study evaluates the effectiveness of locally implantation of mesenchymal stem cell on vertebral bone defects due to infection of mycobacterium tuberculosis. there are controlled participants who receives placebo and patients who receives implantation of MSc