Comparison of Bronchodilator Response From Three Different Aerosol Delivery Methods in Patients With COPD Using Hyperpolarized Xe 129 MRI Ventilation Imaging

Xenon Xe 129 Hyperpolarized MRI Ventilation Imaging for the Evaluation of Treatment Response Comparing Three Different Bronchodilator Aerosol Delivery Methods in Patients With COPD: A Pilot Study

The goal of this clinical trial is to compare responses to bronchodilator treatment delivered by three different aerosol delivery methods in patients with chronic obstructive pulmonary disease (COPD). The main question it aims to answer is whether there are differences in lung ventilation following treatment with each of the three methods as measured using hyperpolarized Xe 129 with MRI.

Participants will:

Receive a standard dose of albuterol delivered using each of 3 aerosol delivery devices. In total, participants will receive three treatments separated by at least 1 week each.

Following each treatment, participants will have inhale an MRI contrast agent called hyperpolarized Xe 129 and will have images of their lungs taken with an MRI.

Researchers will compare the different lung images taken after each treatment to see if there are differences in the distribution of air in the lungs (known as ventilation).

Study Overview

• Status: Recruiting
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Albuterol Sulfate, 2.5 Mg/3 mL (0.083%) Inhalation Solution; Device: Vibrating Mesh Nebulizer; Device: Metered Dose Inhaler; Device: Jet Nebulizer

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22947
      • Recruiting
      • University of Virginia Sheridan Snyder Translational Fontaine Research Unit
      • Contact: Roselove Roselove Nunoo-Asare; Phone Number: 434-243-6074; Email: rnn3b@virginia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years at enrollment.
2. Participant (or legally acceptable representative) willing and able to provide written informed consent.
3. Able (in the Investigator's opinion) and willing to comply with all study requirements.

4. Documented diagnosis of COPD limited to:

   a. Pulmonary function tests (PFT) value of forced expiratory volume at 1 second/forced vital capacity (FEV₁ / FVC) <70%

5. Receiving standard of care (SOC) background drug therapy as per current guidance for COPD for at least 6 months to screening Visit 1.

6. Participants enrolled as bronchodilator responder:

   a. Increase of ≥12% and ≥200 mL as an absolute value compared with a baseline measure in either forced expiratory volume at 1 second or FVC at screening.

7. Participants enrolled as non-bronchodilator responder:

   a. Increase of ≤12% and ≤200 mL as an absolute value compared with a baseline in either FEV1 or FVC at screening.

8. Stable baseline conditions and no medication changes within 6 weeks of planned imaging visit.
9. Female participants of childbearing potential must be confirmed non-pregnant via serum or dip-stick urine test at baseline (Screening) and prior to each Xe MRI.

Exclusion Criteria:

1. Participant with life expectancy <1-2 years or significant diseases other than COPD.

   A significant disease is defined as a disease or condition which, in the opinion of the investigator, may put the patient at risk because of participation in the study or may influence either the results of the study or the patients' ability to participate in the study.

2. Any condition which, in the opinion of the Investigator, would make it unsafe or unsuitable for the patients to undergo MRI (for example: presence of an implanted or external MRI unsafe device that cannot be removed, body weight exceeding table limitations, inability to lie flat, or severe claustrophobia).
3. Inability to hold breath 10-15 seconds for required imaging or for completion of diffusing capacity of lung for carbon monoxide (DLCO) measurements.
4. Respiratory infection of exacerbation of COPD within the 6 weeks prior to screening.
5. Malignancy for which the patient has undergone resection, radiation, or chemotherapy within the last 5 years. Patients with treated basal cell carcinoma are allowed.
6. Known hypersensitivity to any of the study products.
7. Known or planned pregnancy.
8. Participation in another study which, in the opinion of the Investigator, would interfere with the study compliance, or outcome assessments or would prohibit the collection of the required data points.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vibrating Mesh Nebulizer First; Participants will receive albuterol delivered via vibrating mesh nebulizer as their first treatment, followed by albuterol delivered via metered dose inhaler and then albuterol delivered via jet nebulizer.	Drug: Albuterol Sulfate, 2.5 Mg/3 mL (0.083%) Inhalation Solution; Aerosolized albuterol; Device: Vibrating Mesh Nebulizer; A vibrating mesh nebulizer will be used to deliver aerosolized albuterol; Other Names: Solo VMN; Device: Metered Dose Inhaler; A metered dose inhaler will be used to deliver aerosolized albuterol; Other Names: pMDI-aerosol metered dose inhaler; Device: Jet Nebulizer; A jet nebulizer will be used to deliver aerosolized albuterol; Other Names: JN nebulizer
Experimental: Jet Nebulizer First; Participants will receive albuterol delivered via jet nebulizer as their first treatment, followed by albuterol delivered via vibrating mesh nebulizer and then albuterol delivered via metered dose inhaler.	Drug: Albuterol Sulfate, 2.5 Mg/3 mL (0.083%) Inhalation Solution; Aerosolized albuterol; Device: Vibrating Mesh Nebulizer; A vibrating mesh nebulizer will be used to deliver aerosolized albuterol; Other Names: Solo VMN; Device: Metered Dose Inhaler; A metered dose inhaler will be used to deliver aerosolized albuterol; Other Names: pMDI-aerosol metered dose inhaler; Device: Jet Nebulizer; A jet nebulizer will be used to deliver aerosolized albuterol; Other Names: JN nebulizer
Experimental: Metered Dose Inhaler First; Participants will receive albuterol delivered via metered dose inhaler as their first treatment, followed by albuterol delivered via jet nebulizer and then albuterol delivered via vibrating mesh nebulizer.	Drug: Albuterol Sulfate, 2.5 Mg/3 mL (0.083%) Inhalation Solution; Aerosolized albuterol; Device: Vibrating Mesh Nebulizer; A vibrating mesh nebulizer will be used to deliver aerosolized albuterol; Other Names: Solo VMN; Device: Metered Dose Inhaler; A metered dose inhaler will be used to deliver aerosolized albuterol; Other Names: pMDI-aerosol metered dose inhaler; Device: Jet Nebulizer; A jet nebulizer will be used to deliver aerosolized albuterol; Other Names: JN nebulizer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilation Defect Percent	A measure of the percentage of lung area with low ventilation measured using hyperpolarized Xe 129 MRI	measured immediately postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distribution of ventilated space	A measure of distribution of lung ventilation measured using hyperpolarized Xe 129 MRI	measured at baseline and immediately postdose
Membrane uptake of Xe 129	A measure of lung membrane air conductance measured using hyperpolarized Xe 129 MRI	measured at baseline and immediately postdose
Red blood cell Xe 129 transfer	A measure of red blood cell uptake of Xe 129 measured using hyperpolarized Xe 129 MRI	measured at baseline and immediately postdose

Collaborators and Investigators

• Sponsor: Polarean, Inc.
• Collaborators: Aerogen
• Investigators: Principal Investigator: Jaime Mata, PhD, University of Virginia

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: February 14, 2024
• First Submitted That Met QC Criteria: February 14, 2024
• First Posted (Estimated): February 21, 2024

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Chronic Disease; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol
• Other Study ID Numbers: POL-Xe-005

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: Yes
• Studies a U.S. FDA-regulated device product: Yes