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

Study Overview

• Status: Active, not recruiting
• Conditions: Nontuberculous Mycobacterial Lung Disease

Detailed 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.

• Study Type: Observational
• Enrollment (Actual): 109

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia, Division of Infectious Disease

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Observational study of patients with Nontuberculous Mycobacterial lung disease. A subset of newly and prior diagnosed NTM lung disease patients, that have started initial therapy within the last 3 months, and prior diagnosed NTM lung disease patients who have not been on therapy for at least 5 years, will be enrolled in the pharmacokinetics study (Aim 2).

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: University of Virginia

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2020
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: March 3, 2022
• First Submitted That Met QC Criteria: March 3, 2022
• First Posted (Actual): March 14, 2022

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases
• Other Study ID Numbers: IRB200232

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No