Prospective Healthcare-Associated Links in Transmission of Nontuberculous Mycobacteria

NCT ID: NCT05686837

Last Updated: 2025-10-17

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-12-28
• Study Completion Date: 2027-12-31

Brief Summary

Pulmonary NTM infection is recognized as one of the most challenging infections to treat among people with cystic fibrosis (PwCF), notable for prolonged treatment courses and often poor response to therapy. Positive cultures for NTM occur in about 20% of children and adults with cystic fibrosis (CF). However, the source of NTM infection, modes of transmission, and exposure risks are poorly understood. It is thought that NTM is primarily acquired from environmental sites including soil and water as well as water supply systems to homes, hospitals, and clinics and from aerosols generated by flowing water from taps, showers, and fountains. Nonetheless, no direct molecular link has been established between environmental NTM and respiratory CF NTM. Healthcare-associated transmission of NTM among CF patients has been suspected and is of growing concern for CF Centers worldwide. Widespread global transmission of NTM, potentially via person-to-person transmission of fomites and aerosols has been reported. The parent HALT NTM study developed and published a standardized epidemiologic outbreak toolkit for investigation of healthcare-associated NTM outbreaks in CF Care Centers. The investigators are now moving to a prospective investigation, with the long-term goal of real-time early identification and mitigation of potential NTM outbreak investigations coupled with healthcare environmental sampling and home of residence watershed analysis of PwCF identified as belonging to an NTM cluster and receiving care at a single CF Care Center.

Detailed Description

This is a prospective, multicenter, nonrandomized study to investigate potential NTM outbreaks in the six CF Care Centers currently enrolled in the HALT NTM study. The study will investigate potential episodes of healthcare-associated NTM transmission and/or acquisition within participating U.S. Care Centers, coupled with healthcare environmental sampling and home of residence watershed analysis.

PART A / Epidemiologic Investigation:

The Colorado NTM Outcome Measure Advancement Core National Resource Centers (CO-NRC) provides a national reference laboratory for CF NTM. NTM respiratory isolates received from CF Care Centers around the U.S. undergo culture, molecular identification, antimicrobial susceptibility, and whole genome sequencing (WGS). Using this approach, the CO-NRC has identified clusters of NTM isolates, defined as highly similar strains at the genomic level, harbored by two or more people with CF (pwCF) who are cared for at the same CF Care Center. These identifications have heightened the concern for potential healthcare-associated NTM acquisition originating from patient-to- patient transmission or a common environmental source within Centers.

Using integrated clinical and epidemiological research methods, the parent HALT NTM study developed and validated a healthcare-associated epidemiologic investigation toolkit that can identify overlaps in source(s) of care between patients with highly similar NTM isolates in a Center. The parent HALT NTM toolkit facilitates a stepwise process by which individual Centers perform epidemiologic evaluation of patients identified by the CO-NRC as being infected with clustered NTM isolates.

The retrospective parent HALT NTM study of potential NTM outbreaks has been completed at six participating CF Care Centers. In the pHALT NTM study, participating sites will prospectively submit all respiratory NTM isolates from all PwCF receiving routine care over a two-year period to NJH Advanced Diagnostic Laboratories. All NTM isolates will be stored in the Biobank within the NTM Culture, Biorepository and Coordinating Core (Project ID: HS3149) and used for research purposes. The CO-NRC will utilize an honest broker to de-identify NTM isolates and will culture, bank, and extract DNA. The CO-NRC de-identified isolates will then be analyzed as previously described.

When highly related clusters are identified, the HALT NTM epidemiologic investigation toolkit will be independently used by each participating Center to identify overlaps in source(s) of care between patients with highly similar NTM isolates. Additionally, PwCF identified as being infected with highly similar NTM isolates will be asked to complete an online survey. The survey will ask the subject's basic demographic information, query their interactions with other PwCF, and document where they receive CF care.

PART B / Dust and Water Biofilm Collection:

Clustered NTM isolates could originate from a shared healthcare water source. Biofilms from healthcare dust and water supplies will be collected and NTM recovered, identified, and sequenced to determine if the respiratory CF NTM strain genotype is similar to those recovered from the healthcare dust and water supply.

Part C/Home of Residence Watershed Mapping: Clustered NTM isolates could originate from a shared home of residence water supply. PwCF having clustered NTM isolates will be asked to complete an online survey. The survey will ask subjects for their current and last 2 year's home address. The home of residence for PwCF identified in clusters will be extracted and geocoded to latitude and longitude coordinates and mapped to Hydrologic Unit Code level watersheds to determine if clustered PwCF share a common home of residence water supply source.

Conditions

Cystic Fibrosis; Nontuberculous Mycobacterial Pulmonary Infection

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

People infected with NTM isolates identified in a cluster

All people with CF infected with NTM respiratory isolated identified in a cluster based on whole genome sequencing of the core genome will undergo epidemiologic investigation and home of residence watersheds will be mapped.

No interventions assigned to this group

People infected with NTM isolates not identified in a cluster

All people with CF infected with NTM respiratory isolated not identified in a cluster based on whole genome sequencing of the core genome will undergo epidemiologic investigation and home of residence watersheds will be mapped.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Diagnosis of CF consistent with the 2017 CFF guidelines.
• Male or female participant of any age who has a history of NTM or a first positive NTM culture collected as part of routine clinical care from expectorated sputum, induced sputum, throat/oropharyngeal swab and/or bronchoalveolar lavage.

Exclusion Criteria

• No diagnosis of CF

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cystic Fibrosis Foundation

OTHER

Sponsor Role: collaborator

National Jewish Health

OTHER

Sponsor Role: collaborator

University of Texas at Tyler

OTHER

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jane E. Gross, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

National Jewish Health

Denver, Colorado, United States

Johns Hopkins Cystic Fibrosis Center

Baltimore, Maryland, United States

Dell Children's Ascension

Austin, Texas, United States

UT Southwestern Medical Center

Dallas, Texas, United States

The University of Vermont Medical Center

Colchester, Vermont, United States

UVA Health University Medical Center

Charlottesville, Virginia, United States

UW Medical Center

Seattle, Washington, United States

Countries

United States

References

Gross JE, Fullmer J, McCleland G, Caceres SM, Poch KR, Hasan NA, Jia F, Epperson LE, Lipner EM, Vang CK, Honda JR, Strand MJ, de Moura VCN, Daley CL, Strong M, Nick JA. Genomic and epidemiologic investigation of Mycobacterium abscessus isolates in a cystic fibrosis center to determine potential routes of transmission. J Cyst Fibros. 2025 Aug 8:S1569-1993(25)01526-7. doi: 10.1016/j.jcf.2025.07.003. Online ahead of print.

Reference Type: RESULT

PMID: 40783340 (View on PubMed)

Gross JE, Teneback CC, Sweet JG, Caceres SM, Poch KR, Hasan NA, Jia F, Epperson LE, Lipner EM, Vang CK, Honda JR, Strand MJ, Calado Nogueira de Moura V, Daley CL, Strong M, Davidson RM, Nick JA. Molecular Epidemiologic Investigation of Mycobacterium intracellulare Subspecies chimaera Lung Infections at an Adult Cystic Fibrosis Program. Ann Am Thorac Soc. 2023 May;20(5):677-686. doi: 10.1513/AnnalsATS.202209-779OC.

Reference Type: RESULT

PMID: 36656594 (View on PubMed)

Gross JE, Caceres S, Poch K, Epperson LE, Hasan NA, Jia F, Calado Nogueira de Moura V, Strand M, Lipner EM, Honda JR, Strong M, Davidson RM, Daley CL, Nick JA. Prospective healthcare-associated links in transmission of nontuberculous mycobacteria among people with cystic fibrosis (pHALT NTM) study: Rationale and study design. PLoS One. 2023 Dec 20;18(12):e0291910. doi: 10.1371/journal.pone.0291910. eCollection 2023.

Reference Type: RESULT

PMID: 38117792 (View on PubMed)

Gross JE, Finklea JD, Caceres SM, Poch KR, Hasan NA, Jia F, Epperson LE, Lipner EM, Vang CK, Honda JR, Strand MJ, Nogueira de Moura VC, Daley CL, Strong M, Nick JA. Genomic epidemiology of Mycobacterium abscessus at an adult cystic fibrosis programme reveals low potential for healthcare-associated transmission. ERJ Open Res. 2024 Jul 8;10(4):00165-2024. doi: 10.1183/23120541.00165-2024. eCollection 2024 Jul.

Reference Type: RESULT

PMID: 38978544 (View on PubMed)

Gross JE, Caceres S, Poch K, Hasan NA, Davidson RM, Epperson LE, Lipner E, Vang C, Honda JR, Strand M, Strong M, Saiman L, Prevots DR, Olivier KN, Nick JA. Healthcare-associated links in transmission of nontuberculous mycobacteria among people with cystic fibrosis (HALT NTM) study: Rationale and study design. PLoS One. 2021 Dec 20;16(12):e0261628. doi: 10.1371/journal.pone.0261628. eCollection 2021.

Reference Type: RESULT

PMID: 34929010 (View on PubMed)

Gross JE, Caceres S, Poch K, Hasan NA, Jia F, Epperson LE, Lipner E, Vang C, Honda JR, Strand M, Calado Nogueira de Moura V, Daley CL, Strong M, Davidson RM, Nick JA. Investigating Nontuberculous Mycobacteria Transmission at the Colorado Adult Cystic Fibrosis Program. Am J Respir Crit Care Med. 2022 May 1;205(9):1064-1074. doi: 10.1164/rccm.202108-1911OC.

Reference Type: RESULT

PMID: 35085056 (View on PubMed)

Other Identifiers

HS-3175

Identifier Type: OTHER

Identifier Source: secondary_id

24-2792

Identifier Type: -

Identifier Source: org_study_id