New Technology to Assess Treatment for Chronic Obstructive Pulmonary Disease (COPD)

NCT02826343 | Completed Early Phase 1

• 1 other identifier: 18667
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

First, the investigators will image patients with hyperpolarized xenon (Xe) magnetic resonance imaging (MRI) to develop the technique of hyperpolarized xenon MRI at the University of Virginia (UVA). Magnetic Resonance (MR) sequences will need to be developed and optimized for the equipment at UVA. These sequences will need to be evaluated in healthy adults for comparison with results obtained and in adults with lung diseases to optimize the sequences for the detection and evaluation of lung diseases. The MR pulse sequences need to be optimized for the parameters of a human MR coil and the gas exchange characteristics in healthy and diseased lungs. Second, the investigators propose to exploit the power of Xe129 MRI as a diagnostic tool to monitor therapeutic responses of a combination inhaler, Advair, which contains a long-acting beta-adrenoceptor agonist (LABA) and an inhaled corticosteroid (ICS) - two major classes of the current COPD therapeutics. The investigators will characterize the functional changes of the lungs with COPD at baseline, and investigate the responses of the lungs to the treatment after a three-month trial. Also the investigators will compare corresponding results obtained by Xe129 dissolved phase (DP) MRI to the results obtained by gadolinium-based dynamic contrast-enhanced perfusion MRI (perfusion MRI) and high resolution computed tomography (HRCT) of the lung to indirectly validate the Xe129 DP MRI technique. The investigators anticipate that the results from this project will greatly improve the investigators understanding of the lung functional responses of COPD subjects to current therapeutics. Also, the investigators expect that this project will provide evidence to consider Xe129 MRI as a diagnostic strategy to assess and monitor therapeutic responses of existing and new pharmaceuticals, and thus Xe129 MRI will stimulate development of novel therapies for COPD in the future

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

COPD

Outcome Measures

Primary Outcomes (2)

• Improvement in pulmonary airflow physiology detected by Xenon129 MRI

  MRI will determine anticipated improvement in patients' airflow limitation correlation ventilation defect.

  From baseline to 3 month post treatment with Advair

• Improvement in pulmonary gas exchange physiology detected by Xenon129 MRI

  Dissolved phase Xe129 of the MRI will determine anticipated improvement in patients' gas exchange capacity in lung tissues correlating with tissue damage caused by COPD.

  From baseline to 3 month post treatment with Advair

Secondary Outcomes (7)

• Improvement in clinical pulmonary function test

  From baseline to 3 month post treatment with Advair

• St. George's Respiratory Questionnaire

  From baseline to 3 month post treatment with Advair

• Baseline Dyspnea Index

  From baseline to 3 month post treatment with Advair

• Transition Dyspnea Index

  From baseline to 3 month post treatment with Advair

• Chronic Respiratory Questionnaire

  From baseline to 3 month post treatment with Advair

Study Arms (1)

COPD Advair

OTHER

Subjects will undergo hyperpolarized xenon MRI with perfusion imaging, before and after a 90 day course of Adair. All subjects belong to one arm and will receive same treatment. Then they are compared at baseline and 3 month post intervention (described below) for within same-subject changes. Subjects will be administered with 1. Hyperpolarized Xenon129 inhalation during MRI twice (at baseline and post 3 month Advair) 2. Gadolinium intravenous contrast during MRI twice (at baseline and post 3 month Advair) 3. Advair diskus: strength 250mcg/50mcg, one puff twice a day for 3 months.

Drug: Xenon129 MRI imaging; Drug: Gadolinium MRI; Drug: Advair (250mcg/50mcg) one puff twice a day

Interventions

Xenon129 MRI imaging DRUG

subjects will receive at baseline and 3 month post Advair intervention (See next intervention)

COPD Advair

Gadolinium MRI DRUG

subjects will receive at baseline and 3 month post Advair intervention (See next intervention)

COPD Advair

Advair (250mcg/50mcg) one puff twice a day DRUG

subjects will receive for 3 month duration between baseline and 3 month post Xenon129 MRI imaging and Gadolinium MRI.

COPD Advair

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects should be at their clinical baseline on the day of imaging
• Subjects must be clinically stable in order to participate in the study
• Smoking history \>10 pack years
• Subjects must not be currently taking Advair or have taken it within 4 weeks prior to screening
• No subject will be withdrawn from Advair to participate in this study
• The subjects with COPD will be categorized according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD severity classification:
• Class 1: forced expiratory volume at one second (FEV1)/forced vital capacity (FVC) \< 70 and FEV1 \> 80% predicted;
• Class 2: FEV1/FVC \< 70 and 50% \< FEV1 \< 80% predicted;
• Class 3: FEV1/FVC \< 70 and 30% \< FEV1 \< 50% predicted;
• Class 4: FEV1/FVC \< 70 and FEV1 \< 30% predicted

You may not qualify if:

• Continuous oxygen use at home
• Blood oxygen saturation of 92% less than as measured by pulse oximetry on the day of imaging
• FEV1 percent predicted less than 25%
• Pregnancy or lactation
• Claustrophobia, inner ear implants, aneurysm or other surgical clips, metal foreign bodies in eye, pacemaker or other contraindication to MR scanning
• Subjects with any implanted device that cannot be verified as MRI compliant will be excluded.
• Chest circumference greater than that of the xenon MR and/or helium coil. The circumference of the coil is approximately 42 inches.
• History of congenital cardiac disease, chronic renal failure, or cirrhosis.
• Inability to understand simple instructions or to hold still for approximately 10 seconds.
• History of respiratory infection within 2 weeks prior to the MR scan
• History of myocardial infarction (MI) , stroke and/or poorly controlled hypertension.
• Known hypersensitivity to albuterol or any of its components, or levalbuterol
• Glomerular filtration rate (GFR) \< 60 ml/min/1.73 m2 or known hypersensitivity to Gd-contrast agents based on a serum creatinine drawn within 30 days of the MRI
• Acute kidney injury
• History of paraproteinemia syndromes such as multiple myeloma

Sponsors & Collaborators

• University of Virginia: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Fluticasone-Salmeterol Drug Combination

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Salmeterol Xinafoate; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Fluticasone; Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Y Michael Shim, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 10, 2016
• First Posted: July 11, 2016
• Study Start: May 1, 2016
• Primary Completion: June 15, 2018
• Study Completion: June 15, 2018
• Last Updated: November 4, 2020

Record last verified: 2020-11

Locations

US (1)