- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06105450
Respiratory Muscle Assesment in COVID-patients Without Hospitalization (RMA-COVID-19)
Potential Role of Diaphragmatic Muscle Weakness as a Cause of Persistent Exertional Dyspnea in Patients With COVID-19 Disease Without Hospitalization
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Since the beginning of the COVID pandemic, more and more recovered patients have a number of persistent symptoms including exertional dyspnea and fatigue even months after recovering from acute coronavirus disease 2019 (COVID-19). These symptoms often cannot be explained because routine clinical diagnoses, including extensive cardiac and pulmonary examinations, do not reveal any relevant abnormalities.
In our previous study (Regmi et al) with 50 patients formerly hospitalized due to acute COVID-19 infection, it was shown that diaphragm muscle weakness contributes to persistent exertional dyspnea about one year after hospitalization for COVID-19, regardless of mechanical ventilation. Additionally, the severity of exertional dyspnea correlated with the extent of diaphragmatic weakness.
Since laboratory findings, pulmonary function tests and cardiological routine examinations did not reveal any significant impairments, this was the first time that a potential pathophysiological correlate is objectively associated with dyspnea in long COVID-19 syndrome. The results of our study were clinically relevant because the persistent symptom burden in patients after surviving COVID-19 infection remains very high. In addition diaphragm training presents itself as a potential therapeutic target, since in other diseases such as COPD, such training has been shown to improve the symptoms. Therefore, the investigators believe that the results provide important perspectives, both for the pathophysiological understanding and for the potential treatment of persistent exertional dyspnea in patients.
However, a considerable gap exists here: a significant number of patients who suffer from an acute COVID-19 infection but do not have a severe course during the initial infection, so that hospitalization is not necessary, still complain of different persistent symptoms. Here, too, despite an extensive cardiopulmonary work-up, there is a lack of a sufficient explanation of the lasting complaints. It is precisely in these patients that a possible role of diaphragmatic weakness on the symptoms is yet to be investigated using already established gold standard techniques.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Jens Spiesshoefer, MD
- Phone Number: 37065 +4924180
- Email: mdreher@ukaachen.de
Study Contact Backup
- Name: Michael Dreher, Professor
- Phone Number: 88763 +4924180
- Email: jspiesshoefe@ukaachen.de
Study Locations
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NRW
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Aachen, NRW, Germany
- Jens Spiesshoefer
-
Contact:
- Jens Spiesshoefer
- Email: jspiesshoefe@ukaachen.de
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Patients with COVID-19 infection without hospitalization during the acute infection (n=25)
- Patients aged at least 18 years, who are mentally and physically able to consent and participate into the study
Exclusion Criteria:
- Clinically pre-established cardiovascular disease or other pulmonary diseases which might lead to exertional dyspnea (systolic heart failure, COPD).
- Body-mass-index (BMI) >40
- Expected absence of active participation of the patient in study-related measurements
- Alcohol or drug abuse
- Metal implant in the body that is not MRI compatible (NON MRI compatible pacemaker, implantable defibrillator, cervical implants, e.g. brain pacemakers etc.)
- Slipped disc
- Epilepsy
- Bound to a wheel chair
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Twitch transdiaphragmatic pressure in response to supramaximal magnetic stimulation of the phrenic nerve roots
Time Frame: 1 year
|
Recording of twitch transdiaphragmatic pressure (Unit: Pressure in cmH2O)
|
1 year
|
Respiratory mouth pressures
Time Frame: 1 year
|
Measurement of respiratory (inspiratory and expiratory) mouth pressures (Unit: Pressure in cmH2O)
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Diaphragm ultrasound
Time Frame: 1 year
|
Comprehensive evaluation of diaphragm excursion (amplitude during tidal breathing, sniff maneuver and maximal inspiration in cm, corresponding velocity in cm/sec, respectively) and thickening on ultrasound (thickness at functional residual capacity, at total lung capactiy in cm), Markers of Diaphragm excursion and thickening will be combined to classify diaphragm function as normal, mildly, moderately or severly impaired.
|
1 year
|
Exercise intolerance
Time Frame: 1 year
|
Comprehensive evaluation of symptoms (breathlesness based on NYHA class, on a visual scale ranging from 1-10, respectively) and exercise capacity (6 minute walking distance).
These measurements will be combined to classifiy patients as presenting with exercise intolerance or no exercise intolerance.
|
1 year
|
Lung function
Time Frame: 1 year
|
Comprehensive assessment of lung function by bodyplethysmography (most importantly forced vital capacity, forced expiratory volume after 1 second, intrathoracic gas volume, residual volume) and capillary blood gas analysis (most importantly pO2 in mmHG and pCO2 in mmHG).
These measurements will be combined to classify patients as showing normal, restrictive, obstructive lung function impairment, as being hypoxic, hypercapnic, respectively.
|
1 year
|
EMG
Time Frame: 1 year
|
Diaphragm and accessory respiratory muscle electromyography
|
1 year
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Michael Dreher, Professor, RWTH Aachen University
- Principal Investigator: Jens Spiesshoefer, MD, RWTH Aachen University
- Study Chair: Binaya Regmi, MD, RWTH Aachen University
Publications and helpful links
General Publications
- Sudre CH, Murray B, Varsavsky T, Graham MS, Penfold RS, Bowyer RC, Pujol JC, Klaser K, Antonelli M, Canas LS, Molteni E, Modat M, Jorge Cardoso M, May A, Ganesh S, Davies R, Nguyen LH, Drew DA, Astley CM, Joshi AD, Merino J, Tsereteli N, Fall T, Gomez MF, Duncan EL, Menni C, Williams FMK, Franks PW, Chan AT, Wolf J, Ourselin S, Spector T, Steves CJ. Attributes and predictors of long COVID. Nat Med. 2021 Apr;27(4):626-631. doi: 10.1038/s41591-021-01292-y. Epub 2021 Mar 10. Erratum In: Nat Med. 2021 Jun;27(6):1116.
- Spiesshoefer J, Herkenrath S, Henke C, Langenbruch L, Schneppe M, Randerath W, Young P, Brix T, Boentert M. Evaluation of Respiratory Muscle Strength and Diaphragm Ultrasound: Normative Values, Theoretical Considerations, and Practical Recommendations. Respiration. 2020;99(5):369-381. doi: 10.1159/000506016. Epub 2020 May 12.
- Langer D, Ciavaglia C, Faisal A, Webb KA, Neder JA, Gosselink R, Dacha S, Topalovic M, Ivanova A, O'Donnell DE. Inspiratory muscle training reduces diaphragm activation and dyspnea during exercise in COPD. J Appl Physiol (1985). 2018 Aug 1;125(2):381-392. doi: 10.1152/japplphysiol.01078.2017. Epub 2018 Mar 15.
- Regmi B, Friedrich J, Jorn B, Senol M, Giannoni A, Boentert M, Daher A, Dreher M, Spiesshoefer J. Diaphragm Muscle Weakness Might Explain Exertional Dyspnea 15 Months after Hospitalization for COVID-19. Am J Respir Crit Care Med. 2023 Apr 15;207(8):1012-1021. doi: 10.1164/rccm.202206-1243OC.
- Griffin L, Cafarelli E. Resistance training: cortical, spinal, and motor unit adaptations. Can J Appl Physiol. 2005 Jun;30(3):328-40. doi: 10.1139/h05-125.
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 23-296
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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