M. Avium WGS During Mav-PD Treatment

NCT06266442 | Recruiting

• 1 other identifier: Mav-WGS
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mycobacterium Avium; Mycobacterium Infections, Nontuberculous; Mycobacterium Infections; Nontuberculous Mycobacterial Lung Disease; Respiratory Tract Diseases

Keywords

Nontuberculous mycobacterium; Whole genome sequencing; Mycobacterium avium

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with persistent culture-positive sputum despite antimicrobial therapy

  Whole genome sequencing

  24 months

Secondary Outcomes (2)

• Whether patients with Mav-PD have evidence of polyclonal infection as demonstrated by the presence of >1 strain of M. avium in the pre-treatment sputum or a sputum sample during treatment

  24 months

• Whether there is a source of infection from the home water environment

  24 months

Interventions

Whole genome sequencing testing OTHER

Whole genome sequencing

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients at the Toronto Western Hospital (TWH) Nontuberculous Mycobacterial (NTM) clinic who are to be initiated on therapy for Mav-PD.

You may qualify if:

• Age 18 and older
• Willing to provide informed consent and participate in study procedures
• Residing continuously in Ontario during the past five years
• Mav-PD, either initial or recurrent (previously treated patients will be eligible) five years
• Meet American Thoracic Society (ATS) / Infectious Diseases Society of America (IDSA) NTM disease criteria for Mav-PD

You may not qualify if:

• Lack of an available pre-treatment M. avium isolate in the PHOL isolate bank
• The inability to produce sputum either spontaneously or by induction with nebulized hypertonic saline
• Cavitation \>3 cm internal diameter
• Known macrolide-resistant MAC infection
• HIV infection
• Known diagnosis of cystic fibrosis
• History of solid organ or hematological transplantation
• Severe comorbid illness that is reasonably expected to limit survival to \<24 months
• Residing in mid/north York region (King, Aurora, Newmarket, Whitechurch-Stouffville, East Gwillimbury or Georgina)
• Having moved between regions (Toronto/southern York region vs non-Toronto/York region vs mid-northern York region) within the past 5 years

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Western University, Canada: collaborator
• Public Health Ontario Laboratory, Canada: collaborator

Study Sites (1)

University Health Network

Toronto, Ontario, M5G, Canada

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Sputum and environmental samples, DNA extracts from NTM derived from the patients and their environments

MeSH Terms

Conditions

Mycobacterium avium-intracellulare Infection; Mycobacterium Infections, Nontuberculous; Mycobacterium Infections; Respiratory Tract Diseases

Condition Hierarchy (Ancestors)

Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Theodore Marras, MD

  UHN

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Theodore Marras, MD

CONTACT

416-603-5767; ted.marras@uhn.ca

Matty Mehrabi, BSc, M.Ed

CONTACT

416-603-5726; matty.mehrabi@uhn.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Toronto Western Hospital / University Health Network Nontuberculous Mycobacterial Disease Program, Principal Investigator, Associate Professor

Study Record Dates

• First Submitted: December 27, 2023
• First Posted: February 20, 2024
• Study Start: May 13, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: May 21, 2024

Record last verified: 2024-05

Locations

CA (1)