Effects of Bevespi on Ventilation and Gas Exchange Abnormalities in COPD Assessed by 129Xe MRI (COPD)

Effects of Glycopyrrolate/Formoterol (Bevespi) on Ventilation and Gas Exchange Abnormalities in COPD Assessed by 129Xe MRI

The purpose of this study is to determine whether the new inhaler, Bevespi improves lung function. Magnetic resonance imaging (MRI) using inhaled hyperpolarized 129Xe gas, that can provide useful images of the functioning of the lung will be used as a new measure to determine change in function. The investigator anticipate these images will provide more specific information about lung disease than standard lung function tests in response to treatment.

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Drug: hyperpolarized 129Xe gas MRI; Drug: Bevespi Aerosphere

Detailed Description

The study will characterize ventilation and gas transfer distributions in GOLD II and III COPD patients and assess the potential for these physiological parameters as a novel phenotyping method using Magnetic resonance imaging (MRI) using inhaled hyperpolarized 129Xe gas.

The study will additionally quantify regional ventilation and gas transfer response to glycopyrrolate/formoterol in GOLD II and III COPD patients.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke Asthma, Allergy, and Airway Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical diagnosis of COPD confirmed by post-bronchodilator spirometry demonstrating (forced expiratory volume at 1 second(FEV1)/forced vital capacity (FVC) < 0.70 and forced expiratory volume at 1 second (FEV1) in GOLD 2 or 3 stage (30%≤ (forced expiratory volume at 1 second [FEV1] < 80%)
• Willing and able to give informed consent and adhere to visit/protocol schedules
• Women of childbearing potential must have a negative urine pregnancy test

Exclusion Criteria:

• Upper respiratory tract infection within 6 weeks

• Chronic systemic corticosteroid use > 10 mg/day of prednisone

  • Chronic oxygen use (intermittent or continuous)
  • Previous lung resection surgery or decortication
  • Previous history of pneumothorax
  • Evidence of interstitial, occupational or chronic infectious lung disease by imaging studies
  • History of exposure to occupational or environmental hazards that are known to cause lung diseases
  • For women of child bearing potential, positive pregnancy test
  • Major chronic illnesses which in the judgement of the study physician would interfere with participation in the study

  • Patients who are not willing to withhold COPD inhalers for the run-in period.

    • MRI is contraindicated based on responses to MRI screening questionnaire
    • Subject is pregnant or lactating
    • Respiratory illness of a bacterial or viral etiology within 30 days of MRI
    • Subject has any form of known cardiac arrhythmia
    • Subject does not fit into 129Xe vest coil used for MRI
    • Subject cannot hold his/her breath for 15 seconds
    • Subject deemed unlikely to be able to comply with instructions during imaging

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: single arm; glycopyrrolate/formoterol (Bevespi) 2 puffs twice a day taken for two weeks, started after completion of the study XeMRI. A follow up xeMRI occurs at the end of the two weeks of taking the Bevespi in a Pre-post study design.

Drug: hyperpolarized 129Xe gas MRI; There will be MRI imaging before the treatment with Bevespi and another one 2 weeks after use Bevespi. Images obtained using 129Xe MRI will be compared with standard lung function tests that are used routinely in the clinic, 6 minute walk test that assesses walking ability and several questionnaires that assess shortness of breath and life quality.; Other Names: 129Xe MRI; Drug: Bevespi Aerosphere; There will be MRI imaging before the treatment with Bevespi and another one 2 weeks after use Bevespi.; Other Names: Inhaler

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilation Distribution as Measured by Ventilation Defect+Low Percent	The ventilation distribution as measured by ventilation defect+low percent is to measure the area of the lung that has no air.	Week 2
Barrier Uptake.	Diffusion of Xe gas across the lung membrane into the blood. This measures how well oxygen goes through the lung into the blood.	2 weeks
Red Blood Cell (RBC) Uptake	Amount of Xe gas that enters the blood stream after it diffuses across the lung membrane	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary Function Test - Forced Vital Capacity (FVC)	Forced vital capacity (FVC) is the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible, as measured by spirometry.	2 weeks
Pulmonary Function Test - Forced Expiratory Volume-one Second (FEV1)	FEV1 is a lung airflow measure to assess the amount of air that can be blown out in one second.	2 weeks
Pulmonary Function Test - Total Lung Capacity (TLC)	Total Lung Capacity (TLC) is the volume in the lungs at a maximal inhalation.	2 weeks
Pulmonary Function Test - Residual Volume (RV)	Residual volume (RV) is the volume of air remaining in the lungs after a maximal exhalation.	2 weeks
Pulmonary Function Test - Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)	DLCO measures the ability of oxygen to travel from the air sacs of the lungs to the blood stream.	2 weeks
6-minute Walk Test (6MWT)	The 6-minute walk test (6MWT) measures the distance walked at a natural pace for 6 minutes.	2 weeks
St. George's Respiratory Questionnaire (SGRQ) Score	The SGRQ is used to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from 0 to 100, with higher scores indicating more limitations.	2 weeks
Rating of Perceived Dyspnea (RPD) Scale	A patient reported outcome to measure perceived exertion during physical activity. The RPD scale goes from 0 to 10, where 0 = no shortness of breath at all and 10 = maximal shortness of breath (needing to stop the exercise or activity).	2 weeks
COPD Assessment Test (CAT) Score	Functional measurement for COPD patients. Range of CAT scores from 0-40. Higher scores denote a more severe impact of COPD on a patient's life.	2 weeks

Collaborators and Investigators

• Sponsor: Bastiaan Driehuys
• Investigators: Principal Investigator: Yuh Chin Huang, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2018
• Primary Completion (Actual): November 12, 2019
• Study Completion (Actual): November 12, 2019

Study Registration Dates

• First Submitted: September 29, 2017
• First Submitted That Met QC Criteria: October 24, 2017
• First Posted (Actual): October 27, 2017

Study Record Updates

• Last Update Posted (Actual): January 19, 2021
• Last Update Submitted That Met QC Criteria: December 23, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Congenital Abnormalities
• Other Study ID Numbers: Pro00086693

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: No
• product manufactured in and exported from the U.S.: No