Researching the Effects of Airway Clearance Therapies in Cystic Fibrosis

Study Overview
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Brief Summary
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This is a pilot study investigating the effectiveness and clinical efficacy of airway clearance therapy (ACT) in cystic fibrosis (CF). Enrolled subjects will undergo measurements of mucociliary clearance (MCC) and exhaled biomarkers at baseline and after 3 different forms of ACT: high frequency chest wall oscillatory vest, oscillatory positive expiratory pressure device, and whole-body vibration.

Official Title
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Researching the Effects of Airway Clearance Therapies in Cystic Fibrosis (REACT-CF)

Conditions
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Cystic Fibrosis, Mucociliary Clearance Defect

Intervention / Treatment
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* Other: Baseline (Huff-Cough alone)
* Device: Oscillatory Positive Expiatory Pressure Device
* Device: Whole-Body Vibration Platform
* Device: High Frequency Chest Wall Oscillatory Vest


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults with confirmed diagnosis of cystic fibrosis aged 18 years and older. Exclusion Criteria: Pregnant or lactating women, Individuals with severe lung disease (FEV1 <30%), or with exacerbations of lung disease requiring antibiotics or medication change within four weeks prior to enrolment. Individuals unable to use vest-based HFCWO, OPEP device, or who require oxygen supplementation at rest. Individuals with significant balance or gait impairment preventing them from tolerating being positioned on a vibrating platform.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: All subjects will undergo baseline testing, followed by study procedures for three separate interventions, with subjects randomized into three arms in which a different sequence in which to complete the studies.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sequence A<br>In this arm, the interventions were performed in the following order: Baseline (prior to randomization), Whole body vibration, High Frequency Chest Wall Oscillation (HFCWO, aka Vest or TheVest®), Oscillatory Positive Expiratory Pressure (OPEP) (note this is different than the sequence shown in the example latin square shown in the included protocol, as that was meant to serve as an example -- actual randomization and formulation of the employed latin square / sequence generator was performed following completion of the protocol) | Other: Baseline (Huff-Cough alone)<br>* Subjects will provide two huffs (forced expiratory maneuver with open glottis) followed by a cough every six minutes for a total of six Huff-Coughs.<br>Device: Oscillatory Positive Expiatory Pressure Device<br>* Subjects will use an Areobika® branded OPEP device (10 breaths through highest tolerated resistance) prior to undergoing a Huff-Cough. Subjects will use the device six times every six minutes.<br>* Other names: Aerobika;Device: Whole-Body Vibration Platform<br>* Subjects will be seated on a PowerPlate® whole-body vibration platform for 90 seconds prior to Huff-Cough. Six intervals on the platform will be completed six minutes apart.<br>* Other names: PowerPlate;Device: High Frequency Chest Wall Oscillatory Vest<br>* Subjects will use TheVest® using a standardized Minnesota Protocol divided into six, four-minute segments, each followed by a Huff-Cough.<br>* Other names: TheVest;|
| Active Comparator: Sequence B<br>In this arm, the interventions were performed in the following order: Baseline (prior to randomization), HFCWO, OPEP, Whole body vibration (note this is different than the sequence shown in the example latin square shown in the included protocol, as that was meant to serve as an example -- actual randomization and formulation of the employed latin square / sequence generator was performed following completion of the protocol) | Other: Baseline (Huff-Cough alone)<br>* Subjects will provide two huffs (forced expiratory maneuver with open glottis) followed by a cough every six minutes for a total of six Huff-Coughs.<br>Device: Oscillatory Positive Expiatory Pressure Device<br>* Subjects will use an Areobika® branded OPEP device (10 breaths through highest tolerated resistance) prior to undergoing a Huff-Cough. Subjects will use the device six times every six minutes.<br>* Other names: Aerobika;Device: Whole-Body Vibration Platform<br>* Subjects will be seated on a PowerPlate® whole-body vibration platform for 90 seconds prior to Huff-Cough. Six intervals on the platform will be completed six minutes apart.<br>* Other names: PowerPlate;Device: High Frequency Chest Wall Oscillatory Vest<br>* Subjects will use TheVest® using a standardized Minnesota Protocol divided into six, four-minute segments, each followed by a Huff-Cough.<br>* Other names: TheVest;|
| Active Comparator: Sequence C<br>In this arm, the interventions were performed in the following order: Baseline (prior to randomization), OPEP, Whole body vibration, HFCWO (note this is different than the sequence shown in the example latin square shown in the included protocol, as that was meant to serve as an example -- actual randomization and formulation of the employed latin square / sequence generator was performed following completion of the protocol) | Other: Baseline (Huff-Cough alone)<br>* Subjects will provide two huffs (forced expiratory maneuver with open glottis) followed by a cough every six minutes for a total of six Huff-Coughs.<br>Device: Oscillatory Positive Expiatory Pressure Device<br>* Subjects will use an Areobika® branded OPEP device (10 breaths through highest tolerated resistance) prior to undergoing a Huff-Cough. Subjects will use the device six times every six minutes.<br>* Other names: Aerobika;Device: Whole-Body Vibration Platform<br>* Subjects will be seated on a PowerPlate® whole-body vibration platform for 90 seconds prior to Huff-Cough. Six intervals on the platform will be completed six minutes apart.<br>* Other names: PowerPlate;Device: High Frequency Chest Wall Oscillatory Vest<br>* Subjects will use TheVest® using a standardized Minnesota Protocol divided into six, four-minute segments, each followed by a Huff-Cough.<br>* Other names: TheVest;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mucociliary Clearance-274 | As described in the protocol, gamma scintigraphy was used to measure clearance of particles from the whole right lung region of interest over 274 minutes. The primary outcome for this study was the area under the particle clearance curve from time 0 to 274 minutes post-inhalation (normalized to time by dividing by 274) and expressed as a percent, representing total average rate of mucociliary clearance (MCC). | 274 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mucociliary Clearance-90 | As described in the protocol, gamma scintigraphy was used to measure clearance of particles from the whole right lung region of interest over 274 minutes. This outcome for this study was the area under the particle clearance curve from time 0 to 90 minutes post-inhalation (normalized to time by dividing by 90) and expressed as a percent, representing average rate of mucociliary clearance (MCC) over 90 minutes. | 90 minutes | 
| Change in Rate of MCC | Change in slope of particle clearance curve between pre intervention and ACT period. | pre-ACT (0-16 mins) and during ACT (16-50 mins) | 
| Change in Fraction of Exhaled Nitric Oxide (FENO) | FENO measurements were obtained pre- and post- intervention. The difference of post- vs pre- ACT FENO was reported. | pre and immediately post intervention (50 mins post inhalation) | 
| Purine Analysis (AMP) in Exhaled Breath Condensate | Exhaled breath condensate was collected using a commercial device for this purpose. Concentrations of the purine adenosine monophosphate (AMP) and urea in this liquid were determined using mass spectrometry. This outcome was the difference in concentrations of AMP normalized to urea in this exhaled breath condensate between post-ACT and pre-ACT intervention. | pre and immediately post intervention (50 mins post inhalation) | 
| Purine Analysis (Adenosine) in Exhaled Breath Condensate (EBC) | Difference of concentration of adenosine (a purine) in EBC between post-ACT and pre-ACT intervention. | pre and immediately post intervention (50 mins post inhalation) | 
| Purine Analysis (Hypoxanthine) in Exhaled Breath Condensate | Difference of concentration of hypoxanthine (a purine) in Exhaled Breath Condensate between post-ACT and pre-ACT intervention. | pre and immediately post intervention (50 mins post inhalation) |