The Global Tuberculosis Institute (GTBI) was established to advance state-of-the-art care for tuberculosis through excellence in research, practice and teaching. GTBI has successfully conducted multiple protocols and sub-trials for the Centers for Disease Control and Prevention (CDC) Tuberculosis Clinical Trials Consortium (TBTC) and TB Epidemiologic Studies Consortium (TBESC). With extensive experience in domestic field trials and collaborative work in high TB burden countries, GTBI utilizes its unique capacities of scientific expertise and technical assistance to continue its mission to conduct relevant tuberculosis clinical trials and translational research.

Today, as a result of efforts to increase participation in research trials, GTBI has successfully built a network of facilities in Northern New Jersey that opens access to more than 50% of the state’s TB morbidity. The collaboration of Bergen, Hudson, and Middlesex County Health Departments in conjunction with GTBI’s Lattimore Practice has been valuable in helping to advance to much needed research.  With grants from the National Institutes of Health, National Institute of Allergy and Infectious Diseases, New Jersey Health Foundation, and other agencies, over the last nine years GTBI has increased its collaboration with investigators at the Public Health Research Institute (PHRI) and the Division of Infectious Diseases to pursue TB research that encompasses various areas of biomedical investigation and public health.

Correlation between TB clinical status and lipid metabolism of immune cells in adults (Pro2019000730) study aims to find association between TB clinical status and lipid-regulating functions of immune cells isolated from sputum specimens collected from patients with active tuberculosis, latent TB infection (LTBI), and uninfected participants with an overarching hypothesis that blocking foam cell formation will facilitate macrophage-mediated clearance of M. tuberculosis infection. During active TB, the abundance of foam cells correlates with theextent of tissue damage, linking these cells to immunopathology. Foam cells not only contribute to tissue damage, but also facilitate TB transmission. This study may provide important insight and discovery of novel targets in the pro-lipogenic and anti-lipogenic pathways for the development of foam-cell-directed therapeutic interventions to potentiate current TB treatment to shorten the duration of TB treatment and improving TB-related immunopathology. (Principal InvestigatorMaria Laura Gennaro, MD)

Harnessing the human humoral response against TB (Pro20160000116) study is focused on the development of a new TB diagnostic test that has the necessary performance characteristics to detect TB in the urine of the great majority of patients with suspected TB, including patients with or without HIV-1 coinfection. Antibodies directed against a major surface antigen of TB, lipoarabinomannan (LAM) have been found to possess utility for both immunodiagnostic and immunotherapeutic applications. Reagents developed and/or characterized in the Pinter lab have recently contributed to the development of an innovative and sensitive urine test to detect TB in people living with HIV, however these assays are considerably less sensitive in patients without HIV infections, who generally possess lower levels of urinary LAM. Current work is directed at identifying optimal antibody combinations for increased sensitivity and specificity of these reagents so that they can be developed as an effective point-of-care assay for TB infection for a greater percentage of patients, including those without HIV infections. This project may lead to the identification of antibodies that possess greater affinities and novel specificities for TB antigens, and enhanced anti-mycobacterial activities. For therapeutic applications, monoclonal antibodies can be developed into cocktails administered either as purified proteins or by DNA vaccination, providing an adjunct immunotherapeutic approach to standard drug therapies, and a critical alternative in cases ofantibiotic-resistant infections. (Principal Investigator, Abraham Pinter, PhD)

A Phase 2/3, Randomized, Double-blind, Placebo-controlled, Multicenter, Prospective Study to Assess the Efficacy, Safety, and Pharmacokinetics of Orally Administered Epetraborole in Patients with Treatment-refractory Mycobacterium avium Complex Lung Disease (MACrO2) is Sponsored byAN2 Therapeutics, Inc. The purpose of this trial is to learn about the effects of Epetraborole for treatment refractory mycobacterium avium complex, a lung disease resistant to other treatments (refractory MAC). This trial will assess the efficacy, safety, tolerance of study drug and confirm dosage. Adult patients who meet all eligibility criteria including clinical, radiographic, and microbiological criteria and provide their consent will be enrolled and randomly assigned and receive either Epetraborole or a placebo. The trial analyses will include a review of patient-reported outcomes, microbiological, safety, and other data collected at multiple time points. (Site Principal Investigator, Amee Patrawalla, MD)

Computer-aided point-of-care ultrasound for TB active case finding (POCUS-TB) Pro2022001456 is a prospective, observational substudy to Pro2020003026 TBRU/ Halting TB study in Kampala, Uganda, to be overseen by Rutgers principal investigators in collaboration with the Global TB Institute. The purpose of the POCUS-TB study is to generate a high-quality annotated point-of-care ultrasound dataset and optimized POCUS scanning protocol for pulmonary TB screening across the spectrum of early to advanced infection. Additionally, the aim is to develop a computer decision support algorithm for POCUS-based detection by identifying the most relevant measures in a triage screening protocol with the integration of clinical, epidemiologic, and physiometric TB risk variables to help predict TB status. Eligible participants 13 years and older with early to advanced TB or TB-negative individuals who range from healthy to having other respiratory diseases who provide consent will be enrolled. (Principal Investigator, Yingda Xie, MD)