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

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.

Study Overview

• Status: Recruiting
• Conditions: 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 Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Jane E Hill, PhD; Phone Number: 778 879 5105; Email: jane.hill@ubc.ca
• Study Contact Backup: Name: Nina Nouribakikomarolya, PhD; Phone Number: 778 325 5038; Email: nina.Nouribakikomarolya@ubc.ca

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H3N1
      • Recruiting
      • BC Children's Hospital
      • Contact: Jonathan Rayment, MD; Phone Number: 604-875-2345; Email: Jonathan.Rayment@bcchr.ca
      • Contact: Alam Lakhani; Email: Alam.Lakhani@cw.bc.ca
    • Vancouver, British Columbia, Canada, V6Z1Y6
      • Recruiting
      • St. Paul's Hospital
      • Contact: Bradley Quon, MD; Phone Number: 604-787-3536; Email: bradley.quon@hli.ubc.ca
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Completed
      • Phoenix Children's Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Completed
      • Children's Hospital Colorado
    • Denver, Colorado, United States, 80206
      • Completed
      • National Jewish Health
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Not yet recruiting
      • Dartmouth-Hitchcock Medical Center
      • Contact: Brian O'Sullivan, MD; Email: Brian.P.O'Sullivan@hitchcock.org
      • Contact: Kathy Phipps, BA; Phone Number: 8026839291; Email: kathy.j.phipps@dartmouth.edu
  • Ohio
    • Cincinnati, Ohio, United States, 45229-3039
      • Completed
      • Cincinnati Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of British Columbia
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Children's Hospital Colorado; Arizona State University; Cystic Fibrosis Foundation
• Investigators: Principal Investigator: Jane E Hill, PhD, University of British Columbia

Publications and helpful links

Helpful Links

• Public access to study information and clinical site portal.

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2019
• Primary Completion (Estimated): November 30, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: January 21, 2021
• First Submitted That Met QC Criteria: January 29, 2021
• First Posted (Actual): February 3, 2021

Study Record Updates

• Last Update Posted (Estimated): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 2, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: IMPACT; Breath
• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Cystic Fibrosis
• Other Study ID Numbers: 331178/ H20-00071; Pro00043176 (Other Identifier: Advarra); HILL18A0 (Other Grant/Funding Number: Cystic Fibrosis Foundation); R56HL139846 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No