Improving P. Aeruginosa Detection With Breath-based Diagnostics (IMPACT-Breath)

Recruiting

• Conditions: Cystic Fibrosis

• Registration Number: NCT04735952
• Lead Sponsor: University of British Columbia

Brief Summary

The study is a breath biomarker validation study. It is anticipated that 300 patients with cystic fibrosis (CF) from 5 clinical sites in the USA will be enrolled. The study is funded by the US NIH and the US Cystic Fibrosis Foundation. Enrollment commenced in May 2019. Sputum, induced sputum, and oropharyngeal swabs will be collected and evaluated at each clinic as part of standard clinical practice. Excess sputum will be sent to Children's Colorado Hospital for molecular analysis. No swabs will be sent anywhere (other than the clinic from which they originate). Breath samples will be taken from all study participants.

Detailed Description

AIM 1: Refine and validate volatile biomarkers in the breath of adult and pediatric CF patients for detecting established P. aeruginosa lung infections. For each expectorating subject (n ≥ 288; 5 centers), the diagnostic accuracy of the volatile biomarker panel will be tested, with sputum culture as the standard.

AIM 2: Quantify intra-subject breath variability of the target pediatric population. We will collect longitudinal breath samples for two years from P. aeruginosa-negative subjects (n ≥ 58; \~60% non-expectorating) at 4 pediatric CF clinical centers. We will measure intra-subject variance in the breath signatures of expectorating and non-expectorating subjects, with the latter being the target population for the clinical trial. Two to 8 breath samples will be collected per patient.

Study Timeline

• Study Start: 2019-05-03
• Study First Submitted: 2021-01-21
• Study First Submitted QC: 2021-01-29
• Study First Posted: 2021-02-03
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-02
• Last Update Posted: 2023-12-05
• Primary Completion: 2024-11-30
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• Aim 1, Cross-Sectional

IInclusion Criteria:

1. Male or female, ages 8 years and older

2. Diagnosis of CF based on sweat chloride ≥ 60 mmol/L and/or 2 known CF mutations

3. @ BC Children's Hospital only- Non-expectorators are eligible if having a clinically indicated OP swab.

4. FEV1 ≥ 30% predicted for spontaneous expectorators or FEV1 ≥ 40% predicted for subjects undergoing sputum induction

5. Either P. aeruginosa (Pa) negative or chronically infected with P. aeruginosa (Pa positive) as defined below:

   a. P. aeruginosa negative: must meet one of the following criteria: i: No growth of Pa in previous 12 months and ≥ 4 consecutive Pa-negative cultures, OR ii: No history of Pa positive airway cultures (sputum, OP, Bronchoalveolar lavage) b. P. aeruginosa positive i: Over 50% of cultures positive and at least 2 cultures positive for Pa in previous 18 months

6. Willing to participate in and comply with the study procedures and willingness of the subject, parent or legally authorized representative to provide written informed consent.

Exclusion criteria:

1. Age < 8 years
2. Intermittently infected with Pa
3. FEV1 < 30%
4. History of lung transplant
5. Presence of a condition or abnormality that in the opinion of the Principal Investigator would compromise the safety of the subject or the quality of the data.

Aim 2, Longitudinal

Inclusion Criteria, Expectorating Cohort (n=48):

1. Male or female, ages 8-16 years

2. Diagnosis of CF based on sweat chloride ≥ 60 mmol/L and/or 2 known CF mutations

3. @ BC Children's Hospital only- Non-expectorators are eligible if having a clinically indicated OP swab.

4. FEV1 ≥ 30% predicted for spontaneous expectorators or FEV1 ≥ 40% predicted for subjects undergoing sputum induction

5. P. aeruginosa negative, based on one of the following criteria:

   1. No growth of Pa in previous 12 months and ≥ 4 consecutive Pa-negative cultures
   2. No history of Pa positive airway cultures (sputum, OP, bronchoalveolar lavage)

6. Willing to participate in and comply with the study procedures and willingness of the subject, parent or legally authorized representative to provide written informed consent.

Exclusion criteria:

1. Age < 8 years
2. Intermittently or chronically infected with Pa
3. Unable to expectorate sputum or undergo sputum induction
4. FEV1 < 30%
5. History of lung transplant
6. Presence of a condition or abnormality that in the opinion of the Principal Investigator would compromise the safety of the subject or the quality of the data.

Inclusion Criteria, Non-Expectorating Cohort (n=10):

1. Male or female, ages 3-8 years

2. Diagnosis of CF based on sweat chloride ≥ 60 mmol/L and/or 2 known CF mutations 3. FEV1 ≥ 30%

3. Unable to expectorate sputum 5. P. aeruginosa negative, based on one of the following criteria:

4. No growth of Pa in previous 12 months and ≥ 4 consecutive Pa-negative cultures

5. No history of Pa positive airway cultures (sputum, OP, bronchoalveolar lavage) 6. Willing to participate in and comply with the study procedures and willingness of the subject, parent or legally authorized representative to provide written informed consent.

Exclusion criteria:

1. Age < 3 years
2. Intermittently or chronically infected with Pa
3. FEV1 < 30%
4. History of lung transplant
5. Presence of a condition or abnormality that in the opinion of the Principal Investigator would compromise the safety of the subject or the quality of the data.

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Differences in concentrations of individual volatile biomarkers and combinations of biomarkers in breath samples obtained from persons with and without P. aeruginosa lung infections	Enrollment thru 2023. Last Longitudinal Study Visit will be 24 months after last AIM 2 enrollment	Measured using comprehensive two-dimensional gas chromatography of exhaled breath compared to sputum culture (gold standard)

Secondary Outcome Measures

Name	Time	Method
Intra-subject changes in concentrations of individual volatile biomarkers and combinations of biomarkers in breath samples	Thru end of 2025	Breath samples obtained over a duration of two years, measured using comprehensive two-dimensional gas chromatography of exhaled breath

Trial Locations

Locations (7)

Cincinnati Children's Hospital; 🇺🇸 Cincinnati, Ohio, United States

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States

National Jewish Health; 🇺🇸 Denver, Colorado, United States

Phoenix Children's Hospital; 🇺🇸 Phoenix, Arizona, United States

BC Children's Hospital; 🇨🇦 Vancouver, British Columbia, Canada

Dartmouth-Hitchcock Medical Center; 🇺🇸 Lebanon, New Hampshire, United States

St. Paul's Hospital; 🇨🇦 Vancouver, British Columbia, Canada