Trial Outcomes & Findings for Imaging Regional Lung Defect Severity (NCT NCT01640288)

Last Updated: 2020-06-17

Results Overview

Determine quantitative measures of lung ventilation performance in terms of direct measures of gas trapping measured during washout of the perfluorinated gas mixture. Measurement of 'gas trapping' was accomplished using fractional lung volume fast and slow filling compartments. Fractional lung volumes are derived from the MRI (lung volume with fast or slow filling/total MR volume elements in the lung field defined by the gas imaging). All data is normalized per subject to the total lung volume of each subject to eliminate bias due to gender, race, age as is required in global pulmonary function tests. Subaim 2: Compare global pulmonary function tests (PFT's) with gas mean wash-in and washout time constants.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

171 participants

Primary outcome timeframe

Study Duration: < 1hr for MRI (Magnetic Resonance Imaging), < 1 Hr for HRCT (High Resolution Computed Tomography), < 1 hr for PFT's (Pulmonary Function Tests)

Results posted on

2020-06-17

Participant Flow

An open label study in subjects with normal lung function and subjects diagnosed with chronic obstructive pulmonary disease (COPD) over five years. We recruited 100 normal subjects (non-, ex- and current smokers with normal PFT's) and 71 subjects with COPD (varies stages of GOLD I-IV (Global Initiative for Obstructive Lung Disease).

Participant milestones

Participant milestones
Measure	Normal Subjects Subjects with Normal Lung Function by Pulmonary Function Tests (e.g. Spirometry) with or without smoking as a risk factor (non-smokers, ex-smokers, current smokers) Perfluorinated Gas/Oxygen Mixture: 19-Fluorine (19F) MRI of the lungs with 21%/79% Oxygen/Perfluorinated Gas, ≤ 25 liters, gas, single visit, \< 1 hour High Resolution CT of the Chest: High Resolution CT of the Chest, single visit	Subjects With COPD Subjects diagnosed with COPD by GOLD criteria. Perfluorinated Gas/Oxygen Mixture: 19-Fluorine (19F) MRI of the lungs with 21%/79% Oxygen/Perfluorinated Gas, ≤ 25 liters, gas, single visit, \< 1 hour High Resolution CT of the Chest: High Resolution CT of the Chest, single visit
Overall Study STARTED	100	71
Overall Study Received Allocated Intervention	70	48
Overall Study Did Not Receive Allocated Intervention	26	18
Overall Study COMPLETED	70	48
Overall Study NOT COMPLETED	30	23

Reasons for withdrawal

Reasons for withdrawal
Measure	Normal Subjects Subjects with Normal Lung Function by Pulmonary Function Tests (e.g. Spirometry) with or without smoking as a risk factor (non-smokers, ex-smokers, current smokers) Perfluorinated Gas/Oxygen Mixture: 19-Fluorine (19F) MRI of the lungs with 21%/79% Oxygen/Perfluorinated Gas, ≤ 25 liters, gas, single visit, \< 1 hour High Resolution CT of the Chest: High Resolution CT of the Chest, single visit	Subjects With COPD Subjects diagnosed with COPD by GOLD criteria. Perfluorinated Gas/Oxygen Mixture: 19-Fluorine (19F) MRI of the lungs with 21%/79% Oxygen/Perfluorinated Gas, ≤ 25 liters, gas, single visit, \< 1 hour High Resolution CT of the Chest: High Resolution CT of the Chest, single visit
Overall Study Equipment Failure or Poor Image Quality	4	5
Overall Study Screen Failure	20	18
Overall Study Withdrawn by PI	5	0
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Imaging Regional Lung Defect Severity

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Normal Subjects n=100 Participants Subjects with Normal Lung Function by Pulmonary Function Tests (e.g. Spirometry) with or without smoking as a risk factor (non-smokers, ex-smokers, current smokers) Perfluorinated Gas/Oxygen Mixture: 19-Fluorine (19F) MRI of the lungs with 21%/79% Oxygen/Perfluorinated Gas, ≤ 25 liters, gas, single visit, \< 1 hour High Resolution CT of the Chest: High Resolution CT of the Chest, single visit	Subjects With COPD n=71 Participants Subjects diagnosed with COPD by GOLD criteria. Perfluorinated Gas/Oxygen Mixture: 19-Fluorine (19F) MRI of the lungs with 21%/79% Oxygen/Perfluorinated Gas, ≤ 25 liters, gas, single visit, \< 1 hour High Resolution CT of the Chest: High Resolution CT of the Chest, single visit	Total n=171 Participants Total of all reporting groups
Age, Customized Age	42.9 years STANDARD_DEVIATION 14.97 • n=5 Participants	67.7 years STANDARD_DEVIATION 8.54 • n=7 Participants	53.2 years STANDARD_DEVIATION 17.2 • n=5 Participants
Sex: Female, Male Female	47 Participants n=5 Participants	30 Participants n=7 Participants	77 Participants n=5 Participants
Sex: Female, Male Male	53 Participants n=5 Participants	41 Participants n=7 Participants	94 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	96 Participants n=5 Participants	71 Participants n=7 Participants	167 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	40 Participants n=5 Participants	15 Participants n=7 Participants	55 Participants n=5 Participants
Race (NIH/OMB) White	52 Participants n=5 Participants	55 Participants n=7 Participants	107 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Study Duration: < 1hr for MRI (Magnetic Resonance Imaging), < 1 Hr for HRCT (High Resolution Computed Tomography), < 1 hr for PFT's (Pulmonary Function Tests)

Population: 118 subjects successfully received the perfluorinated gas/oxygen imaging agent with acceptable images

Outcome measures

Outcome measures
Measure	Normal Subjects n=70 Participants Subjects with Normal Lung Function by Pulmonary Function Tests (e.g. Spirometry) with or without smoking as a risk factor (non-smokers, ex-smokers, current smokers) Perfluorinated Gas/Oxygen Mixture: 19-Fluorine (19F) MRI of the lungs with 21%/79% Oxygen/Perfluorinated Gas, ≤ 25 liters, gas, single visit, \< 1 hour High Resolution CT of the Chest: High Resolution CT of the Chest, single visit	Subjects With COPD n=48 Participants Subjects diagnosed with COPD by GOLD criteria, specifically FEV1/FVC. Perfluorinated Gas/Oxygen Mixture: 19-Fluorine (19F) MRI of the lungs with 21%/79% Oxygen/Perfluorinated Gas, ≤ 25 liters, gas, single visit, \< 1 hour High Resolution CT of the Chest: High Resolution CT of the Chest, single visit
Gas Trapping Measured During Washout of the Perfluorinated Gas Mixture. Fractional Lung Volume Fast Component 19F MRI	0.718 percentage of total lung volume Standard Error 0.024	0.541 percentage of total lung volume Standard Error 0.216
Gas Trapping Measured During Washout of the Perfluorinated Gas Mixture. Fractional Lung Volume Slow 19F MRI	0.308 percentage of total lung volume Standard Error 0.022	0.451 percentage of total lung volume Standard Error 0.026

SECONDARY outcome

Timeframe: ≤ One hour

Population: Of the baseline participants,118 subjects received the intervention, imaging lung function with the perfluorinated gas/oxygen agent.

Determine ventilation defect severity (VDS) by comparing regional gas signal during wash-in of the perfluorinated gas mixture to steady state in the same cohort. VDS is described as follows. The signal intensity is evaluated at the pixel level at the first image frame (computed from the modeled data) and normalized to the steady state signal intensity (peak signal from the modeled data). This yields a normalized score ranging from 0 to 1. The mean VDS is computed from all pixels in the lung field for each subject in each arm. The two arms are compared

Outcome measures

Outcome measures
Measure	Normal Subjects n=70 Participants Subjects with Normal Lung Function by Pulmonary Function Tests (e.g. Spirometry) with or without smoking as a risk factor (non-smokers, ex-smokers, current smokers) Perfluorinated Gas/Oxygen Mixture: 19-Fluorine (19F) MRI of the lungs with 21%/79% Oxygen/Perfluorinated Gas, ≤ 25 liters, gas, single visit, \< 1 hour High Resolution CT of the Chest: High Resolution CT of the Chest, single visit	Subjects With COPD n=48 Participants Subjects diagnosed with COPD by GOLD criteria, specifically FEV1/FVC. Perfluorinated Gas/Oxygen Mixture: 19-Fluorine (19F) MRI of the lungs with 21%/79% Oxygen/Perfluorinated Gas, ≤ 25 liters, gas, single visit, \< 1 hour High Resolution CT of the Chest: High Resolution CT of the Chest, single visit
Ventilation Defect Severity During wash-in of the Perfluorinated Gas Mixture	0.388 score on a scale Standard Error 0.014	0.504 score on a scale Standard Error 0.017

OTHER_PRE_SPECIFIED outcome

Timeframe: < 1hr

Population: 5 CT datasets could not be analyzed with the IMBIO software and were excluded from further analysis for this subaim.

Compare gas trapping with air trapping by HRCT quantitatively with % lung volume with normal, functional or persistent status determined by thresholds of Hounsfield units.

Outcome measures

Outcome measures
Measure	Normal Subjects n=64 Participants Subjects with Normal Lung Function by Pulmonary Function Tests (e.g. Spirometry) with or without smoking as a risk factor (non-smokers, ex-smokers, current smokers) Perfluorinated Gas/Oxygen Mixture: 19-Fluorine (19F) MRI of the lungs with 21%/79% Oxygen/Perfluorinated Gas, ≤ 25 liters, gas, single visit, \< 1 hour High Resolution CT of the Chest: High Resolution CT of the Chest, single visit	Subjects With COPD n=49 Participants Subjects diagnosed with COPD by GOLD criteria, specifically FEV1/FVC. Perfluorinated Gas/Oxygen Mixture: 19-Fluorine (19F) MRI of the lungs with 21%/79% Oxygen/Perfluorinated Gas, ≤ 25 liters, gas, single visit, \< 1 hour High Resolution CT of the Chest: High Resolution CT of the Chest, single visit
Subaim 1.1: Compare Gas Trapping With Air Trapping by HRCT Normal Lung Density	90.7 percentage of Lung volume at CT density Standard Error 2.68	64.2 percentage of Lung volume at CT density Standard Error 3.07
Subaim 1.1: Compare Gas Trapping With Air Trapping by HRCT Functional Lung Density	8.97 percentage of Lung volume at CT density Standard Error 2.25	28.07 percentage of Lung volume at CT density Standard Error 2.57
Subaim 1.1: Compare Gas Trapping With Air Trapping by HRCT Persistent Lung Density	0.102 percentage of Lung volume at CT density Standard Error 0.95	7.4 percentage of Lung volume at CT density Standard Error 1.09

Adverse Events

Normal Subjects

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Subjects With COPD

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

H. Cecil Charles, Ph.D.

Duke University School of Medicine, Department of Radiology

Phone: 919-684-7921

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place