Clinical trial NCT06105450: Respiratory Muscle Assesment in COVID-patients Without Hospitalization
Official title: Potential Role of Diaphragmatic Muscle Weakness as a Cause of Persistent Exertional Dyspnea in Patients With COVID-19 Disease Without Hospitalization
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Covid19
Diaphragm Injury
Keywords: Respiratory muscle functtion
Lead sponsor: RWTH Aachen University
Sponsor class: OTHER
First posted: 2023-10-27
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: A total of 25 patients will be enrolled. Patients from the outpatient clinic of Department of Pneumology and Intensive Care UKA Aachen with a COVID infection at least six months ago without the need for hospitalization during the initial infection phase. Those patients will be compared with healthy controls (availaible data from pre-covid era) matched in a 3:1 ratio for age, sex and body mass index (BMI).

Brief summary: Fatigue and exercise intolerance after survived COVID-19-infection might be related to weakness of the respiratory muscles. The aim of the project is to measure respiratory muscle function and strength in our respiratory physiology laboratory in patients who were not hospitalized during the acute COVID-19-infection but still complain of different persistent symptoms including exertional dyspnea and fatigue.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Twitch transdiaphragmatic pressure in response to supramaximal magnetic stimulation of the phrenic nerve roots
timeFrame: 1 year
measure: Respiratory mouth pressures
timeFrame: 1 year
Secondary outcomes:
measure: Diaphragm ultrasound
timeFrame: 1 year
measure: Exercise intolerance
timeFrame: 1 year
measure: Lung function
timeFrame: 1 year
measure: EMG
timeFrame: 1 year
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Jens Spiesshoefer
state: NRW
Study officials:
affiliation: RWTH Aachen University
name: Michael Dreher, Professor
role: STUDY_DIRECTOR
affiliation: RWTH Aachen University
name: Jens Spiesshoefer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: RWTH Aachen University
name: Binaya Regmi, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.