Clinical Research Directory

Dolutegravir/Lamivudine Dual Therapy for ART-naïve People With HIV and TB Receiving Rifampin-based TB Treatment

This will be a Phase IIIb Clinical Trial, an international multicenter, randomized, three-arm, non-comparative trial of efficacy, safety, and tolerability of the dual therapy regimen dolutegravir plus lamivudine either twice daily or DTG/3TC ( Dovato) in the morning +dolutegravir (DTG) in the evening, versus standard of care (SOC) twice-daily dolutegravir plus 2 once-daily Nucleoside reverse-transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate /lamivudine (TDF/3TC), among antiretroviral therapy (ART)-nave individuals with HIV-1 receiving rifampin-based TB therapy

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.

Early Empiric Anti-Mycobacterium Tuberculosis Therapy for Sepsis in Sub-Saharan Africa

In sub-Saharan Africa, tuberculosis (TB) is the etiology of 25-50% of bloodstream infections (BSIs) and the leading cause of sepsis among people living with HIV. TB BSI is associated with 20-50% mortality, and 20-25% of deaths occur within five days of admission. TB BSI is difficult to identify clinically and microbiologically. Given that the high prevalence of TB BSI is under-recognized, most patients with sepsis in sub-Saharan Africa do not receive early anti-TB therapy. The hypothesis of this study is that immediate and optimally dosed anti-TB therapy will improve 28 day mortality in patients with sepsis in Uganda and Tanzania. Therefore, the overall goal is to conduct a phase 3 multi-site open label 2x2 factorial clinical trial of 1) empiric immediate initiation of anti-TB therapy plus standard care compared to diagnosis dependent anti-TB therapy plus standard care and 2) sepsis-specific dose anti-TB therapy plus standard care compared to conventional WHO weight-based dose anti-TB therapy plus standard care for the treatment of sepsis in people living with HIV admitted to our longstanding collaborative research sites at either the Mbarara Regional Referral Hospital in Mbarara, Uganda, or Kilimanjaro region hospitals in Moshi, Tanzania.

Effects of Adjunct Omega-3 Long Chain Polyunsaturated Fatty Acids in Pulmonary Tuberculosis Patient: an Early Bactericidal Activity and Inflammatory Trial

The goal of this randomized controlled trial is to evaluate the early bactericidal activity, early inflammatory response, and safety of omega-3 long chain polyunsaturated fatty acid (n-3 PUFA) supplementation in adult patients (aged 18- 45 years) with newly diagnosed, bacteriologically confirmed drug-sensitive pulmonary tuberculosis. The main questions it aims to answers are: * Does adjunct n-3 LCPUFA supplementation reduce the sputum culture time to positivity * Does it improve inflammatory markers and TB treatment outcomes compared to placebo Researchers will compare daily supplementation with \~2g n-3 LCPUFA (EPA and DHA ) to placebo (high linoleic sunflower oil) to determine effects on bactericidal activity, inflammation, and clinical outcomes. Participants will: * Be randomly assigned to receive either n-3 LCPUFA or Placebo daily for 8 weeks with the intensive phase of TB treatment * Attend clinical visit baseline, and follow up visit mostly weekly for 2 months and then monthly for 4 months of the continuous phase of TB treatment * Provide blood, sputum and urine samples for biomarkers and metabolomic analysis * Undergo assessments of iron status, body composition and muscle strength

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.

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.

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.

Trial to Evaluate the Efficacy, Safety and Tolerability of BPaMZ in Drug-Sensitive (DS-TB) Adult Patients and Drug-Resistant (DR-TB) Adult Patients

To evaluate the efficacy, safety and tolerability at 8 weeks (2-months), 52 weeks (12-months), and 104 Weeks (24-months) post the start of the following treatment regimens in participants with: Drug Sensitive TB (DS-TB) patients given BPaMZ for 17 Weeks ( or 4 months) vs. Standard HRZE/HR treatment given for 26 weeks (or 6 months) and Drug Resistant TB (DR-TB) patients given BPaMZ for 26 Weeks (or 6 months)

Pharmacokinetic and Pharmacodynamic Study of High-Dose Rifapentine and Moxifloxacin for Treatment of Tuberculosis

The Tuberculosis Trials Consortium (TBTC) Study 31 is a phase 3 trial evaluating rifapentine-containing regimens for treatment-shortening of drug-susceptible pulmonary tuberculosis. This pharmacokinetic/pharmacodynamic (PK/PD) substudy evaluates rifapentine and moxifloxacin exposure-response relationships for efficacy and safety outcomes. Intensive and sparse PK sampling are performed among participants receiving rifapentine-containing regimens. PK and clinical outcomes data are used to characterize population pharmacokinetics and assess relationships between drug exposure, culture conversion, treatment failure or relapse, and adverse events.

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.

Pharmacokinetic Properties of Antiretroviral and Anti-Tuberculosis Drugs During Pregnancy and Postpartum

The purpose of this study was to evaluate the pharmacokinetic (PK) properties of antiretroviral (ARV) and anti-tuberculosis (TB) drugs administered during pregnancy and postpartum.

Effectiveness and Cost-Effectiveness of Depression Treatment for Individuals With TB in South Africa

This hybrid type I effectiveness-implementation trial will increase understanding of the effectiveness and cost-effectiveness of integrating a brief evidence-based treatment for major depressive disorder (MDD) within the tuberculosis (TB) care platform to improve TB and MDD. Findings from this R01 are likely to inform policy and treatment guidelines for the integrated management of TB and MDD in low- and middle-income countries globally.

A Study to Investigate the Repeat-dose Pharmacokinetics of a Combined Oral Contraceptive When Given Alone and in Combination With Ganfeborole in Female Participants of Non-childbearing Potential

This study is designed to assess the pharmacokinetics (PK), safety, and tolerability of Ganfeborole and Microgynon, an oral contraceptive containing ethinylestradiol (EE) and levonorgestrel (LNG), when Microgynon is administered alone and in combination with Ganfeborole in healthy female participants of non-childbearing potential.

Alternative Diagnoses in Patients About to Start Empiric Tuberculosis Treatment

This study is being conducted to determine whether in patients who are diagnosed with tuberculosis on a clinical basis (where tuberculosis is not found in the sputum) might have other lung diseases than tuberculosis. Depending on the precise nature of your complaints, additional investigations shall be requested by the study investigators. Possible additional investigations will include laboratory tests on samples of your blood, an additional chest X-ray, lung function testing (where you will have to blow air into a machine, so that your lung capacity is registered), CT-scan, and bronchoscopy. The information obtained through the investigations done in this study will help in the management of your illness and other patients who are diagnosed with tuberculosis on a clinical basis.

Antigen-specific Cytotoxic T Cells in the Treatment of Opportunistic Infections

Epstein Barr Virus (EBV) or Cytomegalovirus (CMV) infection results in significant morbidity and mortality in hematopoietic stem cell transplantation (HSCT) patients. HSCT patients often face opportunistic infections due to the immunosuppressive state during transplantation. Antimicrobial drugs are usually used for prophylactic purposes and for treatment after early detectable infections. Unfortunately, some patients develop resistance to such drug treatment. In addition to HSCT patient, immune compromised patient may also be victim to opportunistic infections. Many infections can be effectively managed by functional immune recovery. In this study, the safety and efficacy of microbial-specific cytotoxic T lymphocytes (CTLs) will be investigated.

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.

Safety and Immunogenicity of VPM1002 Vaccination or BCG Revaccination Against TB in Pre-Adolescents Living With and Without HIV in South Africa

The purpose of this study is to assess whether Mycobacterium bovis rBCGΔureC::hly (VPM1002) vaccination and Mycobacterium bovis bacille Calmette-Guérin (BCG) revaccination are safe and immunogenic in pre-adolescents with and without HIV and with and without Mycobacterium tuberculosis (M.tb) sensitization.

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 Step Forward for Unraveling the Immune Mechanisms and Tools for Tuberculosis Spectrum Management

Tuberculosis (TB) is a significant infectious disease worldwide, with millions of people infected and major impact on mortality and public health. TB-SPECTRUM project will conduct a clinical study to characterize better clinically, microbiologically, and immunologically the spectrum of TB across the different stages of infection, including incipient and asymptomatic/subclinical TB, active disease, and post treatment phases. Passive and active case-finding (ACF) clinical approaches will be implemented, recruiting TB patients through public and private healthcare facilities and targeted community outreach, as well as their close contacts. This approach will allow the study of biomarker profiles associated with infection risk, disease progression and response to treatment. The specific objectives of the study will be: * To unravel immune mechanisms underlying the TB spectrum through a multidisciplinary approach. * To perform a clinical study (passive and ACF) for recruiting patients and their contacts for the enrolment of incipient/subclinical TB forms and the subsequent immune characterization and management. * To characterize host systemic and local immune responses on different TB immune states (with special focus on incipient, subclinical and cured TB) to better understand host-pathogen interactions and the established cellular/humoral immune mechanisms. * To stratify host immunity according to patient's clinical strain characterization and disease severity. * To develop and evaluate innovative tools for better management of all phases of the TB spectrum.

ThiPhiSA: New Pathways to Prevention From Community TB Screening in South Africa

This study will compare community-delivered, multi-month dispensing of tuberculosis preventive therapy (TPT) to standard-of-care clinic-based TPT delivery in a population of South African adults who are recommended to receive TB preventive therapy. We hypothesize that persons receiving multi-month dispensing of TPT in the community will have a higher rate of TPT completion at 3 months than persons receiving TPT via standard of care with monthly clinic-based refills.

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.

Targeted Universal TB Testing With Simultaneous TPT Prescribing Among People Living With HIV in South Africa

Background: In 2023, the South African Department of Health introduced targeted universal TB testing (TUTT) at antiretroviral therapy (ART) initiation (irrespective of the presence of TB symptoms). Guidelines regarding TPT initiation in the setting of TUTT are conflicting - recommending either (1) delaying TPT initiation for all patients until a negative TB test result is returned or (2) delaying TPT only for those patients with a positive TB symptom screen. The new TUTT approach along with ambiguity in the timing of TPT initiation has the potential to substantially reduce timely TPT initiation - missing the period of highest TB risk. In modelling approaches for TB screening and TPT delivery, the investigators found that waiting for a sputum result could decrease TPT prescribing from the current level to approximately 17-31%. A novel alternative is to provide TPT at the time of TB testing to all patients initiating or re-initiating ART (TUTT-PT). Those who test positive for TB (5-8% of patients) would be promptly contacted and switched to anti-TB treatment. The investigators model suggests that this strategy could ensure that almost 90% of patients receive TPT and are tested for TB simultaneously. The viability of such an approach depends on demonstrating the safety and effectiveness of TPT for all vs the standard of care. Guiding the optimal implementation strategy for TPT delivery - balancing high-levels of TPT prescribing with rapid diagnosis and treatment initiation for active TB disease - is essential to ensure the continued success of South Africa's TPT program. The investigators are conducting a one-year study built onto Fedisa PreventTB to compare the proposed novel approach of universal TPT to the standard approaches to inform further TPT policy and optimize the effectiveness of the Fedisa PreventTB behavioral economics approach in light of the new TB testing approach. The overall aim is to pilot test the effectiveness and safety of targeted universal TB testing with simultaneous TPT (TUTT-PT) to increase TPT initiation among PLHIV initiating (or re-initiating) ART and to characterize clinic level implementation determinants among health care workers.