Radiation Injury
Conditions
Keywords
Radiation induced lung injury, Xenon gas, hyperpolarized
Brief summary
The purpose of this study is to determine whether magnetic resonance imaging (MRI) using inhaled hyper polarized xenon-129 (129Xe) gas, and conventional contrast can help visualize impaired lung function and detect changes over time in patients receiving treatment as well as those who don't. 129Xe is a special type of xenon gas and when inhaled during MRI may be able to show areas of abnormal thickening of parts of the lungs. These images combined with images taken with injected contrast agents or other special types of MRI such as conventional proton (1H) MRI may provide a better way to look at lung structure and function. The ultimate goal is to predict the degree of radiation-induced lung injury that will develop in a given patient for a given treatment plan. The investigators anticipate that these images will provide more specific information about lung disease than standard lung function tests. The use of 129Xe MRI is investigational. Investigational means that these tests have not yet been approved by the US Food and Drug Administration and are only available in research studies like this one. In addition, standard MRI with contrast is not typically done as standard of care for monitoring changes due to thoracic radiation therapy, therefore, its use in this study is also considered investigational. Healthy volunteers are being asked to participate in this study because to develop a database of functional images that are representative of healthy lungs.
Interventions
Hyperpolarized xenon will be administered in multiple doses in volumes up to 25% of subject total lung capacity (TLC) followed by a breath hold of up to 15 seconds. Subsequent 129Xe doses will only be administered once the subject is ready to proceed.
DEVICEMRI
Conventional 1H MRI will be used to provide anatomical reference scans, as well as pulmonary perfusion.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Bastiaan Driehuys
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
for Patients: 1. Patient scheduled to undergo thoracic RT at Duke University to a dose of at least 20 Gy 2. Willing and able to give informed consent and adhere to visit/protocol schedules
Exclusion criteria
for Patients: 1. Subject is less than 18 years old 2. MRI is contraindicated based on responses to MRI Screening questionnaire 3. Subject is pregnant or lactating 4. Respiratory illness of a bacterial or viral etiology within 30 days of MRI 5. Subject has any form of known cardiac arrhythmia 6. Subject does not fit into 129Xe vest coil used for MRI 7. Subject cannot hold his/her breath for 15 seconds 8. Subject deemed unlikely to be able to comply with instructions during imaging 9. Medical or psychological conditions which, in the opinion of the investigator, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pulmonary Function, as Measured by Ventilation Defect Percentage (VDP) | Baseline, following radiation treatment (up to 3 months) | Ventilation is defined as the regional 129Xe airspace signal divided by the top 1% of 129Xe airspace signal (representing open-airway ventilation). A Ventilation Defect is defined as any region of lung where the Ventilation signal is more than 2 standard deviations below the mean Ventilation signal of healthy volunteer subjects' lungs. Ventilation Defect Percentage, or VDP, is defined as the volume of a subject's Ventilation Defects divided by the volume of the subject's lung, multiplied by 100%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Gas Exchange Defect Percentage (EDP) Following RT (Radiation Treatment) | Baseline, following RT (up to 3 months) | Gas exchange is defined as the ratio of the signal from 129Xe transiently bonding with hemoglobin in the pulmonary capillaries to the local 129Xe airspace signal. In other publications, the investigators have referred to this as RBC (red blood cell) transfer. A Gas Exchange Defect is defined as any region of lung where the Gas Exchange signal is more than 2 standard deviations below the mean Gas Exchange signal of healthy volunteer subjects' lungs. Gas Exchange Defect Percentage, or EDP, is defined as the volume of a subject's Gas Exchange Defects divided by the volume of the subject's lung, multiplied by 100%. |
| RBC (Red Blood Cell) to Barrier Ratio Following RT | Baseline, following RT (up to 3 months) | RBC:barrier ratio is defined as the ratio of the whole lung signal from 129Xe transiently bonding with hemoglobin in the pulmonary capillaries to the whole lung signal from 129Xe in the alveolar barrier tissue. |
| Change in High Barrier Uptake Percentage (HBUP) Following RT | Baseline, following RT (up to 3 months) | Barrier Uptake is defined as the ratio of the regional signal from 129Xe dissolved in the interstitial space within the alveolar walls to the regional signal from 129Xe in the adjacent airspaces. High Barrier Uptake is defined as any region of lung where the Barrier Uptake signal is more than 2 standard deviations above the mean Barrier Uptake signal of healthy volunteer subjects' lungs. High Barrier Uptake Percentage, or HBUP, is defined as the volume of a subject's lung exhibiting High Barrier Uptake divided by the total volume of the subject's lung, multiplied by 100%. |
Other
| Measure | Time frame |
|---|---|
| Change in Perfusion Defect Percentage (PDP) Following RT | Baseline, following RT (up to 3 months) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Patients Scheduled to Undergo Radiation Therapy (RT) Patients scheduled to undergo Radiation Therapy (RT) for lung cancer, or other malignancies such as breast cancer or lymphoma that involve significant irradiation of the thoracic cavity.
Hyperpolarized 129-Xenon gas: Hyperpolarized xenon will be administered in multiple doses in volumes up to 25% of subject total lung capacity (TLC) followed by a breath hold of up to 15 seconds. Subsequent 129Xe doses will only be administered once the subject is ready to proceed.
MRI: Conventional 1H MRI will be used to provide anatomical reference scans, as well as pulmonary perfusion. | 17 |
| Healthy Volunteers Hyperpolarized 129-Xenon gas: Hyperpolarized xenon will be administered in multiple doses in volumes up to 25% of subject total lung capacity (TLC) followed by a breath hold of up to 15 seconds. Subsequent 129Xe doses will only be administered once the subject is ready to proceed.
MRI: Conventional 1H MRI will be used to provide anatomical reference scans, as well as pulmonary perfusion. | 8 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 6 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Patients Scheduled to Undergo Radiation Therapy (RT) | Total | Healthy Volunteers |
|---|---|---|---|
| Age, Continuous | 64.4 years | 54.7 years | 34 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 24 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 17 Participants | 3 Participants |
| Region of Enrollment United States | 17 Participants | 25 Participants | 8 Participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 1 Participants |
| Sex: Female, Male Male | 12 Participants | 19 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 8 |
| other Total, other adverse events | 0 / 17 | 0 / 8 |
| serious Total, serious adverse events | 0 / 17 | 0 / 8 |
Outcome results
Primary
Change in Pulmonary Function, as Measured by Ventilation Defect Percentage (VDP)
Ventilation is defined as the regional 129Xe airspace signal divided by the top 1% of 129Xe airspace signal (representing open-airway ventilation). A Ventilation Defect is defined as any region of lung where the Ventilation signal is more than 2 standard deviations below the mean Ventilation signal of healthy volunteer subjects' lungs. Ventilation Defect Percentage, or VDP, is defined as the volume of a subject's Ventilation Defects divided by the volume of the subject's lung, multiplied by 100%.
Time frame: Baseline, following radiation treatment (up to 3 months)
Population: Subjects that completed visit 1 and visit 2 (n=10) were analyzed. Not applicable to the healthy volunteers group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Scheduled to Undergo Radiation Therapy (RT) | Change in Pulmonary Function, as Measured by Ventilation Defect Percentage (VDP) | -2.20 Ventilation Defect Percentage (VDP) | Standard Error 1.7 |
p-value: 0.22t-test, 2 sided
Secondary
Change in Gas Exchange Defect Percentage (EDP) Following RT (Radiation Treatment)
Gas exchange is defined as the ratio of the signal from 129Xe transiently bonding with hemoglobin in the pulmonary capillaries to the local 129Xe airspace signal. In other publications, the investigators have referred to this as RBC (red blood cell) transfer. A Gas Exchange Defect is defined as any region of lung where the Gas Exchange signal is more than 2 standard deviations below the mean Gas Exchange signal of healthy volunteer subjects' lungs. Gas Exchange Defect Percentage, or EDP, is defined as the volume of a subject's Gas Exchange Defects divided by the volume of the subject's lung, multiplied by 100%.
Time frame: Baseline, following RT (up to 3 months)
Population: Subjects that competed visit 1 and visit 2 (n=10) were analyzed. Not applicable to the healthy volunteers group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Scheduled to Undergo Radiation Therapy (RT) | Change in Gas Exchange Defect Percentage (EDP) Following RT (Radiation Treatment) | 5.20 Gas Exchange Defect Percentage (EDP) | Standard Error 2.6 |
Secondary
Change in High Barrier Uptake Percentage (HBUP) Following RT
Barrier Uptake is defined as the ratio of the regional signal from 129Xe dissolved in the interstitial space within the alveolar walls to the regional signal from 129Xe in the adjacent airspaces. High Barrier Uptake is defined as any region of lung where the Barrier Uptake signal is more than 2 standard deviations above the mean Barrier Uptake signal of healthy volunteer subjects' lungs. High Barrier Uptake Percentage, or HBUP, is defined as the volume of a subject's lung exhibiting High Barrier Uptake divided by the total volume of the subject's lung, multiplied by 100%.
Time frame: Baseline, following RT (up to 3 months)
Population: Subjects that competed visit 1 and visit 2 (n=10) were analyzed. Not applicable to the healthy volunteers group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Scheduled to Undergo Radiation Therapy (RT) | Change in High Barrier Uptake Percentage (HBUP) Following RT | 5.0 Interstitial space to alveolar walls (%) | Standard Error 4 |
Secondary
RBC (Red Blood Cell) to Barrier Ratio Following RT
RBC:barrier ratio is defined as the ratio of the whole lung signal from 129Xe transiently bonding with hemoglobin in the pulmonary capillaries to the whole lung signal from 129Xe in the alveolar barrier tissue.
Time frame: Baseline, following RT (up to 3 months)
Population: Subjects that competed visit 1 and visit 2 (n=10) were analyzed. Not applicable to the healthy volunteers group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Scheduled to Undergo Radiation Therapy (RT) | RBC (Red Blood Cell) to Barrier Ratio Following RT | -0.021 Ratio | Standard Error 0.016 |
Other Pre-specified
Change in Perfusion Defect Percentage (PDP) Following RT
Time frame: Baseline, following RT (up to 3 months)