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

Nontuberculous Mycobacterial Lung Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05277857
• Other study ID #: IRB200232
• Status: Recruiting
• Start date: September 20, 2020
• Est. completion date: December 31, 2026

Study information

• Verified date: May 2022
• Source: University of Virginia
• Contact: Sharon F Johnson
• Phone: 434-982-3413
• Email: sfj8n[@]virginia.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

Description:

Nontuberculous mycobacterial (NTM) lung diseases, primarily due to M. avium complex (MAC), are an increasing clinical problem nationwide and now overtake domestic TB in terms of morbidity and mortality. It is also harder to treat and results in poorer outcomes despite longer drug regimens. In this project we utilize a state-wide clinical cohort of NTM lung disease patients to understand what features of the organism (such as the species or subtype or drug resistance profile), the host (such as antibiotic drug absorption), and the environment (such as household exposure to NTM) are most important in predicting clinical outcome. The sum of this research will direct future therapies and management algorithms for this difficult disease.

First, we will perform whole genome sequencing of NTM isolates to discern relapse versus reinfection and the environmental sources of acquisition. Second, we will utilize a state-wide cohort of new and prior diagnosed NTM lung disease patients, starting initial therapy to correlate clinical outcomes with NTM species, drug susceptibility, other bacterial in vitro assays, and serum drug levels.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 720
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• All subjects:

• Race/ethnicity: any

• Subject has no history of active Tuberculosis in the last 2 years.

• NTM culture positive from respiratory specimen (sputum or bronchial lavage fluid)

• Subject must have an available sputum sample that was taken in the last 2 years. If a sample is not available, the subject must be willing and able to provide a sputum sample.

• Meets the following Infectious Diseases Society of America (IDSA) criteria for NTM lung disease:

• 2 or more sputum (or 1 bronchoscopy/biopsy) cultures positive for "Mycobacterium Avium Complex" or "Mycobacterium abscessus) within the last 2 years.

• Nodules, cavities, and/or bronchiectasis on CT scan within the past 2 years

• If if the above data are not available, but a patient's Infectious Disease or Pulmonary physician has documented the diagnosis of NTM lung disease in their notes, this will suffice

PK subjects:

• Newly diagnosed with NTM lung disease and beginning antibiotics for NTM within the last 3 months from enrollment.

• Prior diagnosis of NTM lung disease, and starting initial therapy within the last 3 months prior to enrollment.

• Consent to pharmacokinetic testing within one month of enrollment and at six months of therapy

Exclusion Criteria:

• List the criteria for exclusion

All subjects:

• Age < 18 years

• Subject has cystic fibrosis or other inherited disorders of airway ciliary dysfunction (eg, primary ciliary dyskinesia)

• Unable to participate in follow-up requirements by phone or clinic visit

PK subjects:

• Unable to have blood drawn for pharmacokinetic testing

Related Conditions & MeSH terms

• Lung Diseases
• Nontuberculous Mycobacterial Lung Disease

Locations

Country	Name	City	State
United States	University of Virginia, Division of Infectious Disease	Charlottesville	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
University of Virginia

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Aim 1	Relapse versus reinfection: Perform whole genome sequencing of NTM isolates from lung disease patients from across Virginia to discern relapse versus reinfection and environmental sources of acquisition.	5 years
Secondary	Aim 2	Patient outcomes: Utilizing the cohort of new and prior diagnosed NTM lung disease patients that have started initial therapy within the last 3 months from across Virginia, compare conventional drug susceptibility (MIC) versus pharmacokinetics/pharmacodynamics (PK/PD) indices in predicting NTM species-specific clinical outcomes.	5 years