Effect of Intrapulmonary Percussion Ventilation on Deposition of Inhaled Aerosols in Idiopathic Pulmonary Fibrosis

Study Overview
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Brief Summary
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This protocol aims to evaluate the feasibility and benefit of Intrapulmonary Percussive Ventilation (IPV) to improve deposition of inhaled radiolabelled aerosols in fibrotic lung regions of patients with Idiopathic Pulmonary Fibrosis (IPF). Phase 1 of the protocol aims to identify the highest IPV pressure that is tolerated by individual patients. Secondary endpoints explore safety of IPV in IPF patients. Phase 2 of the protocol is a crossover randomized trial where patients will inhale 99mTc-labelled DiethyleneTriamine PentaAcetate (DTPA) aerosols with or without IPV. Aerosol deposition in HRCT-defined fibrotic regions of interest (ROI) is described by Single Photon Emission Computed Tomography (SPECT).

Official Title
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Effect of Intrapulmonary Percussion Ventilation on Deposition of Inhaled Aerosols in Idiopathic Pulmonary Fibrosis

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Device: intrapulmonary percussive ventilation
* Radiation: delivery of 99mTc-DTPA aerosol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of IPF according to 2018 ATS/ERS/JRS/ALAT guidelines Affiliation to health insurance Signed informed consent Exclusion Criteria: Other chronic lung disease Airflow obstruction (FEV1/FVC<0.7) History of congestive heart failure History of IPF exacerbation History of lung cancer Chronic cough precluding aerosol delivery and radioprotection Claustrophobia 24h/24 oxygen therapy Any acute lung disease Any potentially transmissible lung infection Current or possible pregnancy and breastfeeding Contra-indications to IPV : Emphysema, recent barotrauma, pneumothorax, pneumomediastinum History of pneumothorax or pneumomediastinum Patient unable to hold a mouthpiece tightly Patient under legal protection (guardianship, curatorship) Contraindication to the administration of Technescan DTPA

Ages Eligible for Study
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Minimum Age: 50 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Phase 1 : Delivery of intrapulmonary percussive ventilation (IPV) to assess for discomfort and adverse effects Phase 2 : Delivery of radiolabelled aerosols with or without IPV, in a crossover design
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Aerosol delivery without intrapulmonary percussive ventilation (Control condition)<br>A radiolabelled 99mTc-DTPA aerosol is generated with a jet nebuliser and is inhaled by the subject through a device (connecting tubes, filters) connecting the nebuliser with 1) a mouthpiece and 2) an intrapulmonary percussive ventilation device which is turned off. Aerosol deposition in fibrotic lung regions is characterized by SPECT imaging. | Radiation: delivery of 99mTc-DTPA aerosol<br>* A 99mTc-DTPA aerosol (500 MBq+/-20%, 3 ml volume) is generated with a jet nebuliser (MMAD 4 µm). The aerosol is inhaled by the study subject and lung deposition is imaged by SPECT<br>|
| Active Comparator: Aerosol delivery with intrapulmonary percussive ventilation (IPV condition)<br>A radiolabelled 99mTc-DTPA aerosol is generated with a jet nebuliser and is inhaled by the subject through a device (connecting tubes, filters) connecting the nebuliser with 1) a mouthpiece and 2) an intrapulmonary percussive ventilation device which is turned on (frequency=1 Hz, pressure to be determined in phase 1 for each patient, in the 5-40 cm H2O range). Aerosol deposition in fibrotic lung regions is characterized by SPECT imaging. | Device: intrapulmonary percussive ventilation<br>* Intrapulmonary percussive ventilation is a non invasive ventilation technique where small boli or air are delivered, at adjustable frequency and pressure, to the upper airways though a mouthpiece. IPV is currently used in the clinic to aid with airway clearance in neuromuscular and airway diseases.<br>Radiation: delivery of 99mTc-DTPA aerosol<br>* A 99mTc-DTPA aerosol (500 MBq+/-20%, 3 ml volume) is generated with a jet nebuliser (MMAD 4 µm). The aerosol is inhaled by the study subject and lung deposition is imaged by SPECT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Discomfort during IPV | IPV is delivered at increasing pressure (from 5 cm H2O to 40 cm H2O maximum pressure) and discomfort is assessed by a 5-level Likert scale ranging from no discomfort to untolerable discomfort. IPV is stopped when discomfort is rated as difficult to tolerate whatever the pressure. | immediately after IPV (visit V1) | 
| Phase 2: Change between Control and IPV condition in amount of 99mTc-labelled DTPA aerosol deposited in fibrotic lung regions, reported to loaded dose | Following aerosol delivery, chest imaging is done with a SPECT device. SPECT images are fused to high resolution computed tomography (HRCT) images. Fibrotic lung regions regions of interest (ROI) are defined by analysis of HRCT images. SPECT signal in fibrotic ROI is reported to the radioactive dose that was loaded in the nebulizer Endpoint is radioactive signal in fibrotic ROI / loaded dose | After delivery of radiolabelled aerosol under both Control and IPV condition (Visit 4/5) i.e. up to 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Sensations associated with IPV in patients with IPF | 5-levels Likert scales ranging from not at all to Very much are used to answer the following questions : I have trouble breathing This thumps to much This is scary | immediately after IPV (Visit 1) | 
| Phase 1: IPV-induced variations in dyspnea | Dyspnea-12 scale | Before IPV (Visit 1) and 15 days after IPV (Visit 2) | 
| Phase 1: IPV-induced variations in cough | Leicester Cough Questionnaire | Before IPV (Visit 1) and 15 days after IPV (Visit 2) | 
| Phase 1: IPV-induced variations in Forced Vital Capacity | Spirometry Forced vital capacity is expressed in liters | Before IPV (Visit 1) and 15 days after IPV (Visit 2) | 
| Phase 1: IPV-induced variations in Carbon monoxide transfer factor (DLCO) | Single breath test DLCO is expressed in mL/min/mmHg | Before IPV (Visit 1) and 15 days after IPV (Visit 2) | 
| Phase 1: IPV-induced variations in 5 Hz respiratory reactance | Impulse oscillometry 5 Hz reactance is expressed as kPa.s/L | Before IPV (Visit 1) and 15 days after IPV (Visit 2) | 
| Phase 1: Incidence of Treatment-Emergent Adverse Events | Symptomatic pneumothorax Acute exacerbation of IPF requiring hospitalization | immediately after IPV (Visit 1) until 15 days after IPV (V2) | 
| Phase 2 : Change between Control and IPV condition in total lung deposition of the 99mTc-labelled DTPA aerosol | Ratio of SPECT in total lung / loaded dose | After delivery of radiolabelled aerosol under both Control and IPV condition (Visit 5) | 
| Phase 2: Ratio of deposition of the 99mTc-labelled DTPA aerosol in fibrotic lung versus normal lung | ROI for normally-appearing lung are defined by HRCT. Endpoint is SPECT signal in fibrotic lung ROI / SPECT signal in normally-appearing lung ROI | After aerosol delivery in the Control condition | 
| Incidence of Treatment-Emergent Adverse Events one month after treatment | Telephone interview to assess for : Symptomatic pneumothorax Acute exacerbation of IPF requiring hospitalization | 1-month after the last aerosol delivery (V6) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aerosol, deposition, Intrapulmonary Percussive Ventilation