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

• Sponsor: University of British Columbia (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04735952
• Collaborator: Arizona State University (Other), Children's Hospital Colorado (Other), National Heart, Lung, and Blood Institute (NHLBI) (NIH), Cystic Fibrosis Foundation (Other)
• Enrollment: 300
• Locations: 5
• Anticipated Duration (Months): 68
• Patients Per Site: 60
• Patients Per Site Per Month: 0.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis

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 Design

• Study Type: Observational
• Anticipated Enrollment: 300 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Improving P. Aeruginosa Detection With Breath-based Diagnostics (IMPACT-Breath)
• Actual Study Start Date: May 3, 2019
• Anticipated Primary Completion Date: Dec 31, 2022
• Anticipated Study Completion Date: Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
AIM 1 No-Intervention. Participants in this group will have 1 study visit only. During that visit, breath and sputum samples will be collected.
AIM 2 No-Intervention. Participants in this group will have up to 8 study visits over a 2 year period. During the study visits, breath and sputum samples will be collected.

Outcome Measures

Primary Outcome Measures

1. 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

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Aim 1, Cross-Sectional

Inclusion 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. Able to expectorate sputum spontaneously or willing to undergo sputum induction procedure

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:

1. 1. 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

1. 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. 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.

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. Able to expectorate sputum spontaneously or willing to undergo sputum induction procedure

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

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

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

7. No history of Pa positive airway cultures (sputum, OP, bronchoalveolar lavage)

8. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
2	Children's Hospital Colorado	Aurora	Colorado	United States	80045
3	National Jewish Health	Denver	Colorado	United States	80206
4	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
5	Cincinnati Children's Hospital	Cincinnati	Ohio	United States	45229-3039

Sponsors and Collaborators

• University of British Columbia
• Arizona State University
• Children's Hospital Colorado
• National Heart, Lung, and Blood Institute (NHLBI)
• Cystic Fibrosis Foundation

Investigators

• Principal Investigator: Jane E Hill, PhD, University of British Columbia

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Public access to study information and clinical site portal.

Publications

None provided.

• Responsible Party: Jane Hill, PhD, Associate Professor, University of British Columbia
• ClinicalTrials.gov Identifier: NCT04735952
• Other Study ID Numbers: 331178/ H20-00071; Pro00043176; HILL18A0; R56HL139846
• First Posted: Feb 3, 2021
• Last Update Posted: Feb 5, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Jane Hill, PhD, Associate Professor, University of British Columbia: Breath; IMPACT
• Additional relevant MeSH terms: Cystic Fibrosis

Study Results

No Results Posted as of Feb 5, 2021