Dual MRI for Cardiopulmonary COVID-19 Long Haulers

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

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.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Drug: Hyperpolarized 129Xenon gas

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

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: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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: subjects with diagnosis of COVID-19 (Long-hauler); 23 subjects with a confirmed diagnosis of COVID-19 infection, and after 60 days or longer	Drug: Hyperpolarized 129Xenon gas; Each xenon dose will be limited to a volume less than 25% of subject lung capacity (TLC),; Other Names: Xe MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Red Blood Cell to Membrane (RBC:M) Ratio	To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery.	1 year
Ventilation Defect Percent	To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery.	1 year
High Membrane Percent	To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery.	1 year
Red Blood Cell (RBC) Defect Percent	To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery.	1 year
Red Blood Cell to Membrane (RBC:M) Ratio at 9 Months	To characterize the evolution of cardiopulmonary abnormalities over 9 months.	9 Months
Ventilation Defect Percent at 9 Months	To characterize the evolution of cardiopulmonary abnormalities over 9 months.	9 months
High Membrane Percent at 9 Months	To characterize the evolution of cardiopulmonary abnormalities over 9 months.	9 months
Red Blood Cell (RBC) Defect Percent at 9 Months	To characterize the evolution of cardiopulmonary abnormalities over 9 months.	9 months
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.	Baseline

Collaborators and Investigators

• Sponsor: Bastiaan Driehuys
• Investigators: Principal Investigator: Loretta Que, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2021
• Primary Completion (Actual): April 20, 2023
• Study Completion (Actual): April 20, 2023

Study Registration Dates

• First Submitted: March 11, 2021
• First Submitted That Met QC Criteria: March 30, 2021
• First Posted (Actual): April 1, 2021

Study Record Updates

• Last Update Posted (Actual): May 6, 2024
• Last Update Submitted That Met QC Criteria: May 3, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: MRI; Hyperpolarized 129Xe
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Anesthetics, Inhalation; Xenon
• Other Study ID Numbers: Pro00107681

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