Clinical Research Directory

Training Protocol on the Natural History of Tuberculosis

Background: \- Tuberculosis (TB) is an infectious disease that affects numerous people worldwide. Researchers are interested in actively recruiting individuals with TB for research and treatment studies. Objectives: \- To collect blood and other samples to study the natural history of tuberculosis. Eligibility: \- Individuals 2 years of age and older who have either active or latent tuberculosis. Design: * Latent TB patients: Participants will have a single study visit with a physical examination and medical history, and will provide blood samples for testing. * Active TB patients: Participants will have an initial visit with a physical examination and medical history, and will provide blood samples for testing. Participants will also provide sputum samples if required, and may have an optional skin punch biopsy to collect a sample of skin tissue for study. * Treatment for active TB will be provided as part of this protocol. * Active TB participants may be asked to return for study visits every 1-2 months while receiving treatment.

PREVAIL VIIIa: Evaluation of Latent Tuberculosis Infection Screening Methods in People Living With Retroviral Infection in Liberia

Background: Tuberculosis (TB) is a health threat for people living with human immunodeficiency virus (HIV). People living with HIV are more likely than others to develop active TB. Also, TB makes HIV progress faster. TB is a leading cause of death among people in the West African country of Liberia. Researchers want to find an effective testing method for latent tuberculosis infection (LTBI) to help people living with HIV in Liberia. Objective: To compare the interferon-gamma release assay (IGRA) and tuberculin skin test (TST) as LTBI screening tests in people living with HIV in Liberia. Eligibility: People ages 18 and older who take part in NIH study #19-I-N014 and are scheduled to have or have had IGRA at a Month 12 HONOR study visit. Design: Participants will be screened with a medical history and physical exam. Their medical records and HONOR study records will be reviewed. Participants will have TST. Purified protein derivative will be placed in the skin of their forearm. They will be observed for adverse reactions for 15 minutes. Between 48 and 72 hours after placement, they will have a second study visit to have the TST read. If they miss this time frame, they can return up to 7 days after placement. If they have a positive test result, they will have a chest x-ray. They will have a third study visit to review the results of the chest x-ray. They will be referred for clinical care if needed. They will take a pregnancy test if needed. Participation will last from 2 days to 6 weeks.

South Africa Smoking Cessation and Engagement in HIV/TB Care Care

The purpose of this study is to integrate elements from existing interventions developed by our team into a single intervention (QUIT-AD), designed to improve smoking cessation and favorable HIV/TB treatment outcomes among individuals with HIV and/or TB in Cape Town, South Africa. If feasibility, acceptability, and preliminary efficacy are demonstrated, the intervention will be ready for large-scale effectiveness/implementation testing. This program will has the potential to dramatically improve public health by increasing the smoking quit rate and facilitating favorable HIV/TB treatment outcomes among patients with HIV and/or TB in resource limited South African settings.

Shortened Regimen for Drug-susceptible TB in Children

While drug-susceptible tuberculosis (TB) disease in children currently requires four to six months of treatment, most children may be able to be cured with a shorter treatment of more powerful drugs. Shorter treatment may be easier for children to tolerate and finish as well as ease caregiver strain from managing treatment side effects and supporting children over many months. The primary objective of this study is to evaluate if a 2-month regimen (including isoniazid (H), rifapentine (P), pyrazinamide (Z) and moxifloxacin (M)) is as safe and effective as a 4- to 6-month regimen (isoniazid, rifampicin (R), pyrazinamide, ethambutol (E)) in curing drug-susceptible TB disease in children under 10 years old. The study is also evaluating the safety of the HPZM in children with and without HIV.

The DECIDE-TB Trial; Validation of Treatment Decision Algorithms for Childhood Tuberculosis

The Decide-TB project aims to generate evidence for the implementation of a comprehensive Treatment Decision Algorithms (TDA) based approach for TB in children living in high TB burden and resource-limited countries, at District Hospital (DH) and Primary Health Centre (PHC) levels, and to facilitate the integration of this evidence within practices and policies. This programmatic pilot led by the National TB Programs (NTP) will test a TDA-based approach integrating TB screening, diagnosis, treatment decision-making, and disease severity assessment for shorter treatment eligibility, for use at a lower level of healthcare. This TDA-based approach will be evaluated in a hybrid effectiveness implementation study based on a pragmatic stepped wedge cluster-randomized trial. The Decide TB project will be implemented at the district level, targeting five districts in each country. Each cluster in a district will be made up of one district hospital and six primary health centers. The study will develop a Clinical Decision Support System (CDSS) to operationalize the use of TDAs, and strengthen District Health Information Systems (DHIS2) to collect individual data, which will contribute to monitoring and evaluation, clinical mentoring, and supervision by the country's NTPs.

Study of a Single Dose of Pretomanid Added to an Optimized Background Regimen in Children With Rifampicin-Resistant Tuberculosis

The purpose of the study is to evaluate the pharmacokinetics (PK), safety, tolerability, and acceptability of a single dose of pretomanid, added to an optimized background tuberculosis treatment regimen (OBR), in children with rifampicin-resistant tuberculosis (RR-TB) with or without human immunodeficiency virus (HIV).

Development of a Clinical-epidemiological Score Predictive of Tuberculosis.

Despite being a curable and preventable disease, tuberculosis still represents a major global health problem. It is estimated that 10.8 million people contracted tuberculosis in 2023, with an incidence of 134 per 100,000 inhabitants. In 2023, there were 1.25 million deaths, confirming this disease as a leading cause of death and the leading cause of death from a single infectious agent. It is a disease that primarily affects adults in their most productive years, with significant repercussions on family budgets. The aim of this study is to identify and characterize the demographic, epidemiological, microbiological, clinical, and radiological variables of the tuberculosis population that has come to our hospital's attention, as an exemplary population in a low-endemic setting. This study also aims to develop a tuberculosis risk score aimed at early differentiation between patients requiring respiratory isolation and those with negligible tuberculosis risk, and to improve diagnostic accuracy.

Peer-led Implementation of TB-HIV Education and Adherence Counseling in Uganda

This cluster-randomized trial in Uganda will evaluate the effectiveness and implementation of a novel, peer-led TB education and counseling strategy to improve outcomes among persons with tuberculosis (TB) with and without HIV/AIDS and assess the social-behavioral mechanisms underlying the observed treatment effects.

Effects of the Active Cycle of Breathing Technique With and Without Balloon Blowing Therapy in Tuberculosis

The study design will be a randomized controlled trial. The data will be collected from Gulab Devi Teaching Hospital, Lahore. 34 kids aged 8 to 14 years will be randomly assigned either to an experimental group or a control group. The intervention group includes the active Cycle of Breathing technique with balloon-blowing therapy for 3 days. The control group includes the active cycle of breathing technique. Sputum secretion will be measured by 'sputum measurement cups." Dyspnea will be measured by the "Modified Borg dyspne Scale," and functional capacity will be measured by the "6-Minute Walk Test." Data will be analyzed through SPSS version 25.0.

A Home-Based Approach to Tuberculosis Preventive Treatment Management

Background: Tuberculosis (TB), though preventable and curable, remains a major public health concern worldwide. While elimination of tuberculosis infection (TBI) is critical to TB elimination, TBI continues to represent a substantial public health burden, particularly among household contacts. In recent years, tuberculosis preventive treatment (TPT) has been recognized as essential to eliminating TB worldwide and is particularly critical for children with TBI or close contacts of individuals with infectious TB. The scale-up of TPT among household contacts has been markedly slow, with only 55% of the coverage target achieved for children under 5 years and only 10% for those over 5 years by 2022, highlighting substantial gaps in preventive intervention implementation. Community- and home-based approaches are proposed solutions to reduce the gaps in early detection and provision of preventive treatment for household contacts in high-TB-burden settings many of whom remain underserved with the usual standard facility care. A home-based approach has not been well evaluated for its effectiveness in real-world settings to inform policy decisions. Given the limited evidence, this study aims to evaluate the effectiveness of a home-based TB contact investigation and preventive treatment management among child household contacts in southern Ethiopia. Objective: This study aims to evaluate the effectiveness of a home-based TB contact investigation and preventive treatment management among child household contacts in Gedeo, South Ethiopia. Methods: A pragmatic, two-arm, parallel, cluster-randomized trial will be conducted in Gedeo, South Ethiopia. The procedures in this trial will be based on eight clinical standards for the diagnosis, treatment, and prevention of TBI, which were defined through a Delphi process by a panel of global experts in tuberculosis care. This trial consists of two study groups: a home-based intervention group and a standard facility-based (usual care) comparison group. Within the intervention group, health extension workers based at health posts in the catchment areas of the selected clusters will receive training focused on the study procedures-the implementation of standardized TB symptom screening protocols, TPT management and adherence support, and safety assessment and reporting. A routine TB care procedure will be implemented in the facilities randomized to the comparison group in accordance with national guidelines. Index patients will be asked to enumerate and bring all children below 15 years of age for TB screening and initiation of preventive treatment or anti-TB treatment accordingly.

Safety and Immune Responses After Vaccination With Two Investigational RNA-based Vaccines Against Tuberculosis in BCG Vaccinated Volunteers

This is a two-part randomized, placebo-controlled, observer-blind, safety and dose-finding Phase Ib/IIa study. This study will evaluate up to four dose levels of the BNT164 investigational vaccines (BNT164a1 and BNT164b1) to select a safe and tolerable dose in a three-dose schedule. This study includes: Part A (Phase Ib) and Part B (Phase IIa).

Evaluating the Safety and Immunogenicity of MTBVAC

The purpose of this study is to evaluate the safety and immunogenicity of MTBVAC in adolescents and adults living with and without HIV in South Africa

Rapid Research in Diagnostics Development for TB Network (R2D2 Kids) and Assessing Diagnostics At POC for TB in Children (ADAPT for Kids)

Every year there are an estimated 230,000 childhood deaths from TB. There is an urgent need for novel tests for TB diagnosis in children under 15 years. The Rapid Research in Diagnostics Development for TB Network (R2D2 Kids) and the Assessing Diagnostics at Point-of-care for Tuberculosis in children (ADAPT for Kids) studies seek to reduce the burden of TB worldwide by evaluating faster, simpler, and less expensive TB triage and diagnostic tests for use in children.

Assessing Diagnostics At Point-of-care for Tuberculosis

Every year, more than 3 million people with TB remain undiagnosed and 1 million die. Better diagnostics are essential to reducing the enormous burden of TB worldwide. The Assessing Diagnostics At Point-of-care for Tuberculosis (ADAPT) study seeks to reduce the burden of TB worldwide by evaluating faster, simpler, and less expensive TB triage and diagnostic tests.

Diagnostic Performance and Safety of Endobronchial Ultrasound-guided Transbronchial Mediastinal Cryobiopsy in Diagnosing Tuberculous Mediastinal Lymphadenitis: a Randomised Controlled Trial

The goal of this clinical trial is to compare the diagnostic efficacy and safety of Endobronchial Ultrasound-guided Transbronchial Mediastinal Cryobiopsy (EBUS-TBMC) versus standard EBUS-guided Transbronchial Needle Aspiration (EBUS-TBNA) in adult patients with suspected mediastinal lymph node tuberculosis. The main questions it aims to answer are: Does EBUS-TBMC provide a superior diagnostic yield for detecting granulomatous inflammation compared to EBUS-TBNA in the same target lymph node? Does the cryopreservation process affect the viability of Mycobacterium tuberculosis for culture, and does the larger tissue sample obtained via EBUS-TBMC enhance the sensitivity of molecular tests such as Xpert MTB/RIF? Is the safety profile of EBUS-TBMC, particularly regarding bleeding complications, comparable to that of EBUS-TBNA in this patient population? Researchers will compare the two biopsy techniques using a paired design within the same patient to see if EBUS-TBMC results in higher rates of positive pathology, microbiology, and molecular diagnoses. Participants will: Undergo both EBUS-TBNA and EBUS-TBMC procedures on the same mediastinal lymph node during a single bronchoscopy session, with the order of procedures randomized. Provide blood and tissue samples for comprehensive testing, including histology, mycobacterial culture, and Xpert MTB/RIF assay. Complete short-term (within 2 hours post-procedure) and 7-day follow-up assessments to monitor for any adverse events. Participate in a 6-month clinical follow-up to establish a final diagnosis, which will serve as the reference standard for evaluating the diagnostic tests.

Alcohol Reduction Among People With TB and HIV in India

The highest incidence of tuberculosis disease (TB) in the world is in India, accounting for 27% of all new cases globally, with approximately 86,000 among persons with HIV (PWH). Unhealthy alcohol use can worsen the health of people who have Tuberculosis (TB), HIV and people who have both TB and HIV. Behavioral interventions that 1) target alcohol use and 2) are integrated into TB and TB/HIV and HIV care may lead to better outcomes. The goal of this study is to test if a behavioral alcohol reduction intervention integrated into TB, TB/HIV and HIV treatment can reduce alcohol use and improve TB and HIV health outcomes among people with unhealthy alcohol use. The aims of the HATHI study are: Aim 1: To test if a 4 session behavioral alcohol reduction intervention, called HATHI, integrated into TB and TB/HIV and HIV Care can decrease unhealthy alcohol use among persons with TB and TB/HIV coinfection and HIV. Aim 2: To test if the HATHI intervention, integrated into TB and TB/HIV and HIV care can improve TB and HIV clinical outcomes; Aim 3: To evaluate barriers and facilitators to integrating HATHI intervention into TB and TB/HIV and HIV care, and to determine the incremental costs of delivering HATHI intervention in TB and HIV clinical settings. Investigators hypothesize that HATHI intervention will reduce alcohol use among persons with TB and TB with HIV and HIV, and that its delivery in the TB and HIV setting will be acceptable to patients and providers and feasible.

MoMa Signature During Granulomatosis

Sarcoidosis is a systemic inflammatory disease characterized by unspecific granuloma formation. Our hypothesis is that granuloma formation and maintenance mainly relies on the overactivation of monocytes (Mo) and macrophages (Ma). To this end, the study aims (i) to define MoMa systemic signature in sarcoidosis, (ii) to characterize this signature in situ on tissue samples, and (iii) to identify causative factors that participate to the MoMa chronic overactivation. Thus, a cohort of sarcoidosis patients will be compared with tuberculosis patients. The MoMa systemic signature will be defined on whole blood (TruCulture model) and then in situ through different methods (multi-parameter spectral flow cytometry, RNA-seq, Luminex, imaging mass cytometry). The epigenome of monocytes will be studied thanks to CUT\&Tag. The MoMa systemic signature will be defined ex vivo at different time points during the course of the disease with phenotypic, transcriptomic, cytokine and functional approaches. The previously identified signature will be studied in situ and completed by the characterization of granuloma architecture and microenvironmental interactions, which could be modulated by epigenetic modifications. Hence, the epigenome of monocytes will be analyzed in two groups (sarcoidosis and tuberculosis). These results would allow to better understand sarcoidosis physiopathology and, in fine, may raise new therapeutic strategies. Finally, the study could challenge the dogma on innate immunity/auto-inflammation versus adaptive immunity/auto-immunity/memory.

Digitally Facilitated, Integrated Community and Facility-Based Interventions: The HEART-TB Trial Protocol

Effective tuberculosis treatment outcome relies on adherence. However, many TB patients struggle to adequately adhere to their prescribed regimen due to various social, economic, personal, and healthcare system barriers. However, previous interventions did not adequately consider combined strategies in a way that addressed social, personal, economic, and health system barriers to case detection, treatment adherence, and outcomes. As a result, the investigator developed novel holistic interventions, which include community-based TB patient support, family and patient adherence support strategies, digital adherence support strategies, and structured training for health care providers. Investigators are now conducting a type II hybrid effectiveness-implementation study to evaluate the effectiveness and implementation of digitally facilitated integrated community- and facility-based interventions on case detection and medication adherence and treatment outcomes among patients on TB treatment in South Ethiopia using the RE-AIM framework.

Paradoxical Tuberculosis Reactions in Patients Without HIV Infection

Background: Most people with tuberculosis (TB) feel better after starting treatment. But for some people, the opposite happens. They may feel better at first, but then suddenly get worse. This is a paradoxical reaction. Researchers want to better understand what causes this reaction and what happens after someone has it. Objective: To learn about paradoxical reactions to TB treatment. Eligibility: Adults 18 and older diagnosed with confirmed or suspected TB and currently on treatment for at least 2 weeks, with or without signs/symptoms of a paradoxical inflammatory reaction. Design: Participants will be screened with a physical exam and medical history. They will give blood and urine samples. Eligible participants will visit either the NIH Clinical Center or the Mexico Clinic sites 3 times over 6 to 18 months. Each visit will take 7 hours to complete; visits may be scheduled over more than 1 day. Participants may have more visits if their TB symptoms change. Participants will give blood, urine, and sputum samples. They will have adverse event assessments. They will have 2 to 3 positron emission tomography/computed tomography (PET/CT) scans. PET/CT scans make pictures of the inside of the body. For this, participants will lie on a table that slides into a donut-shaped scanner. They will get a small amount of radioactive dye through an IV, which is a small plastic tube placed in a vein in the arm using a needle. Participants may have optional apheresis at the NIH site only. For this, blood is taken from a needle in one arm. White blood cells are separated from the rest of the blood. The rest of the blood is returned through a needle in the other arm.

Study to Assess Efficacy and Safety of M72/AS01E-4 Mycobacterium Tuberculosis (Mtb) Vaccine in Adolescents and Adults

The study is a randomized, double-blind, placebo-controlled, multicenter, clinical trial to assess the prophylactic efficacy, safety, and immunogenicity of the investigational M72/AS01E-4 Mtb vaccine when administered intramuscularly (IM) on a 0,1-month schedule to adolescents and adults. This trial will be conducted in 3 cohorts: Interferon gamma release assay (IGRA)-positive Cohort, IGRA-Negative Cohort and Human Immunodeficiency virus (HIV) Cohort.

Asymptomatic TB With Innovative Modified Short-course Regimens

This study is a randomized controlled trial among asymptomatic tuberculosis individuals aiming to assess whether the standard treatment duration can be shortened to 17 weeks without increasing the types or doses of anti-tuberculosis medications or 13 weeks with the high-dose rifapentine and moxifloxacin.

Evaluation and Demonstration of New Tuberculosis Diagnostics for Indonesia

The goal of this cluster-randomised controlled trial (CRCT) is to learn whether the use of new non-sputum-based diagnostic tests and other intervention components for tuberculosis (TB) diagnosis in healthcare facilities (HCF) can increase TB notifications. The main questions it aims to answer are: (1) Does the diagnostic intervention package raise TB notifications by HCF?; (2) Does the diagnostic intervention package raise the proportion of patients with TB who are diagnosed with microbiological tests, lower the time needed for TB diagnosis, lower the number of visits to HCF before TB diagnosis, raise the use of TB tests by healthcare providers, and lower the costs for TB diagnosis? Researchers will compare the diagnostic intervention package provided to HCFs and the community in the intervention arm with the standard of care in the control arm to assess the intervention's effect. Healthcare providers will be trained to provide diagnostic interventions to patients visiting their HCFs and to community residents in the areas surrounding HCFs.

Investigation of the Effects of Oxidized Antigens on the T-Cell Response and the Epigenetic Reprogramming of Neutrophils in Lung Diseases - OXIGENE -

The OXIGENE study is a research project that aims to better understand how the immune system behaves in people with lung diseases such as asthma, COPD, pneumonia, tuberculosis, and viral lung infections. By analyzing a single blood sample, the study examines how certain immune cells react during inflammation and infection, and whether lasting changes in these cells influence how strongly the body responds to disease. Although participants do not receive direct medical benefit, the results may help improve future diagnosis and treatment of lung diseases by providing deeper insight into immune responses.

A Study of Daily Rifapentine Combined With Isoniazid (1HP) for Tuberculosis Prevention in Children Less Than 13 Years of Age With and Without HIV

This study aims to find the proposed dose of Rifapentine (RPT) taken once daily with Isoniazid (INH) for 28 days to prevent tuberculosis (TB). The study will take place at multiple locations and children under 13 years old will be divided into two groups: one group will include children without HIV, and the other group will include children with HIV who are on antiretroviral treatment. Up to 144 children will participate, and participants in each group will be followed for 24 weeks.