Clinical trial NCT04735952: Improving P. Aeruginosa Detection With Breath-based Diagnostics (IMPACT-Breath)
Official title: Improving P. Aeruginosa Detection With Breath-based Diagnostics (IMPACT-Breath)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cystic Fibrosis
Keywords: Breath
IMPACT
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: Arizona State University
name: Children's Hospital Colorado
name: National Heart, Lung, and Blood Institute (NHLBI)
name: Cystic Fibrosis Foundation
First posted: 2021-02-03
Enrollment: 300
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants will have a diagnosis of cystic fibrosis with cultures that are either P. aeruginosa (Pa) negative or Pa positive.

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.

Eligibility criteria: 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%

4. Unable to expectorate sputum 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 \< 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.

Primary outcomes:
measure: Differences in concentrations of individual volatile biomarkers and combinations of biomarkers in breath samples obtained from persons with and without P. aeruginosa lung infections
timeFrame: Enrollment thru 2023. Last Longitudinal Study Visit will be 24 months after last AIM 2 enrollment
Secondary outcomes:
measure: Intra-subject changes in concentrations of individual volatile biomarkers and combinations of biomarkers in breath samples
timeFrame: Thru end of 2025
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Vancouver
country: Canada
facility: BC Children's Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Jane E Hill, PhD
role: PRINCIPAL_INVESTIGATOR
References: