Clinical Research Directory

Clinical Characteristics and Immune Escape Mechanism of Nontuberculous Mycobacterial Lung Disease in South China

Nontuberculous Mycobacterial lung disease (NTM-LD) is a significant infectious challenge. The precise causes remain unclear, diagnosis can be complex, treatment outcomes are often unsatisfactory, and the disease can severely affect a patient's quality of life. Environmental factors, such as the warm and humid climate in South China, may contribute to unique characteristics of NTM in this region, but systematic research is currently lacking. This study aims to improve the understanding of NTM-LD in South China. It consists of two complementary parts: 1. The first part is a retrospective review of medical records from approximately 1,500 NTM patients across multiple hospitals in South China. This analysis seeks to identify common patterns in symptoms, diagnostic findings, and treatment responses within this population. 2. The second part is a prospective study involving about 106 current NTM-LD patients. Blood and lung fluid samples will be collected to analyze, using advanced laboratory techniques, how the patient's immune system responds to the infection. This investigation aims to uncover clues about why some cases are difficult to treat. The overall goal of this research is to generate evidence that can aid healthcare providers in South China in diagnosing and managing NTM-LD more effectively. Please note that this is an observational study; no new drugs or experimental treatments are being tested.

Association of Nutrition and T Cell Immune Activity With Disease Progression in Nontuberculous Mycobacterial Pulmonary Disease

Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic lung infection caused by environmental mycobacteria. The clinical course of NTM-PD varies widely among patients. Some individuals remain stable for long periods without treatment, while others experience worsening lung disease that requires antibiotic therapy or may lead to death. Currently available clinical tools are limited in their ability to predict which patients will experience disease progression. This observational study aims to better understand how the body's immune response and nutritional status are related to disease progression in adults with confirmed or suspected NTM-PD. In particular, the study focuses on T cells, a type of immune cell that plays an important role in controlling mycobacterial infections. Prior research suggests that impaired T-cell function may contribute to disease progression in NTM-PD, but most studies have relied on blood samples rather than immune cells from the lung, where the infection occurs. In this study, immune cells obtained from bronchoalveolar lavage fluid during clinically indicated bronchoscopy will be analyzed to assess inhibitory and exhausted T-cell profiles in the lung. In addition, systemic T-cell function will be evaluated using the mitogen response from the QuantiFERON-TB Gold Plus blood test. Nutritional status and body composition will also be assessed, as poor nutrition is known to affect immune function and disease outcomes. Participants will be followed over time as part of routine clinical care. The primary outcome of the study is the time from enrollment to the initiation of antibiotic treatment due to clinical disease progression. Secondary outcomes include identifying immune predictors of treatment initiation, examining the relationship between nutritional status and immune activity, evaluating changes in body composition and immune markers with disease progression, and determining whether immune and nutritional measures improve prediction of mortality beyond established clinical risk scores. By integrating lung immune profiling, blood-based immune testing, nutritional assessment, and clinical data, this study seeks to improve risk stratification in NTM-PD. The results may help identify patients at higher risk for disease progression and poor outcomes, support more personalized monitoring strategies, and inform future studies targeting immune and nutritional pathways in NTM-PD.

Biomarkers of Phage Treatment Response in NTM and Other Infections

This study aims to identify biomarkers associated with response to phage therapy for refractory bacterial infections. This includes mycobacteriophage treatment for patients with nontuberculous mycobacterial infections. Blood and airway samples will be obtained from follow up visits of patients with refractory bacterial infections that are considered for phage therapy. Samples will be compared between those that receive phage therapy and those that did not. Biomarkers will include changes in the airway microbiome, transcriptome, inflammatory cytokines, and development of neutralizing antibody against phages. The primary endpoint is to identify biomarkers associated with clinical and/or radiographic improvement and/or culture improvement which includes clearing of cultures or decrease in qualitative or resolution of signs and symptoms of infection after at least 6-8 weeks of bacteriophage therapy.

Hypertonic Saline for MAC

The MAC-HS study is a testing whether hypertonic saline helps improve symptoms and clearance of mycobacteria in patients with M. avium complex lung infections.

Hypertonic Saline Inhalation for Mycobacterium Avium Complex Pulmonary Disease

The SALINE trial will investigate the effect of Hypertonic Saline inhalation plus best supportive care on burden of symptoms, clearance of mycobacteria and functional capacities in participants with Mycobacterium avium complex lung disease and compare the effect to treatment with best supportive care alone.

Mycobacteriophage Treatment of Non-tuberculosis Mycobacteria

About 10 people with cystic fibrosis (CF) and persistent Nontuberculosis mycobacteria (NTM) infection despite treatment will be screened to find out if their NTM infection has at least one mycobacteriophage that is effective in killing the mycobacteria. Individuals who are found to have at least one phage will be offered assistance in pursuing FDA approval for treatment via expanded-access Individual New Drug (IND) for compassionate-use. They will receive phage treatment for 1 year along with their guideline-based antibiotics for NTM. Individuals who are not identified as having a phage match will be followed as they continue to receive guideline based antibiotic therapy for 1 year. All subjects, including those who do not have a phage match will continue to be observed for the duration of the study, or about 1 year.

M. Avium WGS During Mav-PD Treatment

This is a prospective observational study using whole genome sequencing (WGS) to investigate whether new strains (other than the initially identified strain(s)) of M. avium are responsible for persistently culture positive sputum during treatment (refractory disease), or the reversion to culture positive sputum after prior conversion to negative. The study will further investigate for differences between participants living in the Toronto/York region versus participants living elsewhere. The primary goal of this prospective observational study is to understand why some patients with M. avium lung disease have persistent or recurrent M. avium in their sputum despite treatment. The aim is to understand whether it is usually due to treatment failure or new infection.

Mycobacterial Lung Diseases in Virginia: Sequencing and Clinical Determinants of Relapse and Outcome

Mycobacterial Lung Diseases in Virginia: sequencing and clinical determinants of relapse and outcome