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Dual MRI for Cardiopulmonary COVID-19 Long Haulers

Characterizing the Long-Term Cardiopulmonary Effects of COVID-19 With Hyperpolarized Xenon and Cardiac MRI

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT04828135
Enrollment
18
Registered
2021-04-01
Start date
2021-05-26
Completion date
2023-04-20
Last updated
2024-05-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Covid19

Keywords

MRI, Hyperpolarized 129Xe

Brief summary

The next phase of the COVID-19 pandemic is likely to see a surge in an associated chronic cardiopulmonary disease that will challenge health systems. Recovered patients are presenting with persistent dyspnea at the Duke Pulmonary Post-COVID clinic. Evidence is now mounting that recovered patients have significant residual pulmonary disease, while myocardial injury has also been increasingly reported. To optimally care for these patients, Duke Pulmonary study team must comprehensively assess and monitor the changes in cardiopulmonary function and relate the changes to physiologic and quality of life outcomes. The study team will deploy cutting-edge MRI to fully characterize cardiopulmonary function in enrolled 30 subjects (accrual 23 subjects) at time point 60-120 days post recovery and 6-9 months later. Cardiac MRI will assess the myocardial status and right ventricular function, while hyperpolarized 129Xe MRI will provide a 3D assessment of pulmonary ventilation, interstitial barrier integrity, and pulmonary vascular hemodynamics. The overall objective outlined in this study is to demonstrate the feasibility and value of comprehensive longitudinal imaging characterization of cardiopulmonary structure and function in patients recovered from Covid-19.

Detailed description

The proposed research builds on the established sensitivity of Hyperpolarized 129Xe MRI to obstructive and pulmonary vascular lung disease, features expected to represented in the Covid-19 cohort. It further incorporates a new understanding of the possible role of myocardial injury in these recovered patients by combining cutting-edge pulmonary and cardiac MRI. Although the initial presentation of patients with moderate to severe symptoms of COVID19 infections is dominated by respiratory symptoms, 10% go on to develop persistent post-infection symptoms which are thought to have an inflammatory etiology. Evidence suggests that pathologic activation of the inflammasome persists beyond the acute initial presentation that contributes to the persistent disabling symptoms characterized as long-haul COVID. For this trial, subjects will be eligible for enrollment if subjects are outpatients with a history of a laboratory-confirmed diagnosis of COVID-19 infection, and after 60 days or longer. The study team will accrual 13 subjects who continue to have respiratory symptoms (i.e., cough, shortness of breath, dyspnea on exertion). An additional 10 subjects engaged in competitive sports and diagnosed with COVID-19 will also be enrolled. These subjects can be asymptomatic or mildly to moderately. Although rare, cardiac impairment has been documented in \<2% of these individuals. The study team knowledge, XeMRI has not yet been studied in this specific patient subset. Existing data highlight significant racial and ethnic disparities with historically underserved minority populations (i.e., Black, LatinX) suffering disproportionately higher infection rates and more severe illness compared to Whites. This is reflected by the population enrolled in the study team RedCAP database and biorepository. As such 30% of subjects enrolled will be required to be from underserved communities.

Interventions

Each xenon dose will be limited to a volume less than 25% of subject lung capacity (TLC),

Sponsors

Bastiaan Driehuys
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE

Intervention model description

This will be a single-blinded open-label study enrolling 30 subjects (accrued 23 subjects (13 subjects who continue to have respiratory symptoms and 10 subjects within competitive sports) with a laboratory-confirmed diagnosis of COIVD-19 infection, and after 60 days or longer

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

Diagnosis of post Coronavirus (COVID-19) Inclusion Criteria: 1. Age ≥ 18-year-old 2. Tested positive for SARS-CoV2 3. Willing and able to give informed consent and adhere to visit/protocol scheduled (consent must be given before any study procedures are performed)

Exclusion criteria

1. Prisoners 2. Pregnant, planning pregnancy, or lactating 3. Conditions that prohibit MRI scanning (metal in eye, claustrophobia, inability to lie supine). 4. 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

Design outcomes

Primary

MeasureTime frameDescription
Red Blood Cell to Membrane (RBC:M) Ratio1 yearTo determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery.
Ventilation Defect Percent1 yearTo determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery.
High Membrane Percent1 yearTo determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery.
Red Blood Cell (RBC) Defect Percent1 yearTo determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery.
Red Blood Cell to Membrane (RBC:M) Ratio at 9 Months9 MonthsTo characterize the evolution of cardiopulmonary abnormalities over 9 months.
Ventilation Defect Percent at 9 Months9 monthsTo characterize the evolution of cardiopulmonary abnormalities over 9 months.
High Membrane Percent at 9 Months9 monthsTo characterize the evolution of cardiopulmonary abnormalities over 9 months.
Red Blood Cell (RBC) Defect Percent at 9 Months9 monthsTo characterize the evolution of cardiopulmonary abnormalities over 9 months.
Identify MRI Features That Predict Physiological Outcomes With DLCO (Diffusing Capacity of the Lungs for Carbon Monoxide)BaselineDLCO is the extent to which oxygen passes from the air sacs of the lungs into the blood.

Countries

United States

Participant flow

Pre-assignment details

Historical Controls were not considered enrolled.

Participants by arm

ArmCount
Participants With Diagnosis of COVID-19 (Long-hauler)
23 participants with a confirmed diagnosis of COVID-19 infection, and after 60 days or longer Hyperpolarized 129Xenon gas: Each xenon dose will be limited to a volume less than 25% of subject lung capacity (TLC),
18
Historical Controls
10 participants with historical Hyperpolarized 129Xenon imaging
10
Total28

Baseline characteristics

CharacteristicParticipants With Diagnosis of COVID-19 (Long-hauler)Historical ControlsTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
3 Participants0 Participants3 Participants
Age, Categorical
Between 18 and 65 years
15 Participants10 Participants25 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants1 Participants1 Participants
Race (NIH/OMB)
Black or African American
0 Participants1 Participants1 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
4 Participants0 Participants4 Participants
Race (NIH/OMB)
White
14 Participants8 Participants22 Participants
Region of Enrollment
United States
18 participants10 participants28 participants
Sex: Female, Male
Female
8 Participants5 Participants13 Participants
Sex: Female, Male
Male
10 Participants5 Participants15 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
1 / 18
other
Total, other adverse events
0 / 18
serious
Total, serious adverse events
3 / 18

Outcome results

Primary

High Membrane Percent

To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery.

Time frame: 1 year

ArmMeasureValue (MEAN)Dispersion
Subjects With Diagnosis of COVID-19 (Long-hauler)High Membrane Percent18.23 percentage of high membraneStandard Deviation 29.4
Historical ControlsHigh Membrane Percent0.5 percentage of high membraneStandard Deviation 1.3
Primary

High Membrane Percent at 9 Months

To characterize the evolution of cardiopulmonary abnormalities over 9 months.

Time frame: 9 months

ArmMeasureValue (MEAN)Dispersion
Subjects With Diagnosis of COVID-19 (Long-hauler)High Membrane Percent at 9 Months15 percentage of high membraneStandard Deviation 30.6
Primary

Identify MRI Features That Predict Physiological Outcomes With DLCO (Diffusing Capacity of the Lungs for Carbon Monoxide)

DLCO is the extent to which oxygen passes from the air sacs of the lungs into the blood.

Time frame: Baseline

ArmMeasureValue (MEAN)Dispersion
Subjects With Diagnosis of COVID-19 (Long-hauler)Identify MRI Features That Predict Physiological Outcomes With DLCO (Diffusing Capacity of the Lungs for Carbon Monoxide)20 percentage of predicted valueStandard Deviation 8
Primary

Red Blood Cell (RBC) Defect Percent

To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery.

Time frame: 1 year

ArmMeasureValue (MEAN)Dispersion
Subjects With Diagnosis of COVID-19 (Long-hauler)Red Blood Cell (RBC) Defect Percent10.6 percentage of RBC defectStandard Deviation 5.6
Historical ControlsRed Blood Cell (RBC) Defect Percent4.2 percentage of RBC defectStandard Deviation 4.8
Primary

Red Blood Cell (RBC) Defect Percent at 9 Months

To characterize the evolution of cardiopulmonary abnormalities over 9 months.

Time frame: 9 months

ArmMeasureValue (MEAN)Dispersion
Subjects With Diagnosis of COVID-19 (Long-hauler)Red Blood Cell (RBC) Defect Percent at 9 Months6.2 percentage of RBC defectStandard Deviation 1.8
Primary

Red Blood Cell to Membrane (RBC:M) Ratio

To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery.

Time frame: 1 year

ArmMeasureValue (MEAN)Dispersion
Subjects With Diagnosis of COVID-19 (Long-hauler)Red Blood Cell to Membrane (RBC:M) Ratio0.39 ratio (RBC:M)Standard Deviation 0.14
Historical ControlsRed Blood Cell to Membrane (RBC:M) Ratio0.51 ratio (RBC:M)Standard Deviation 0.13
Primary

Red Blood Cell to Membrane (RBC:M) Ratio at 9 Months

To characterize the evolution of cardiopulmonary abnormalities over 9 months.

Time frame: 9 Months

ArmMeasureValue (MEAN)Dispersion
Subjects With Diagnosis of COVID-19 (Long-hauler)Red Blood Cell to Membrane (RBC:M) Ratio at 9 Months0.44 ratio (RBC:M)Standard Deviation 0.14
Primary

Ventilation Defect Percent

To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery.

Time frame: 1 year

ArmMeasureValue (MEAN)Dispersion
Subjects With Diagnosis of COVID-19 (Long-hauler)Ventilation Defect Percent2.4 percentage of ventilation defectStandard Deviation 3.5
Historical ControlsVentilation Defect Percent0.6 percentage of ventilation defectStandard Deviation 0.7
Primary

Ventilation Defect Percent at 9 Months

To characterize the evolution of cardiopulmonary abnormalities over 9 months.

Time frame: 9 months

ArmMeasureValue (MEAN)Dispersion
Subjects With Diagnosis of COVID-19 (Long-hauler)Ventilation Defect Percent at 9 Months0.5 percentage of ventilation defectStandard Deviation 0.5

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026