Clinical trial NCT05903001: Diaphragmatic Function as a Biomarker
Official title: Diaphragmatic Function as a Biomarker in Patients With Respiratory Diseases
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Dyspnea; Asthmatic
COPD
Fibrosis
Pulmonary Hypertension
Asthma
Dyspnea
Keywords: dyspnea
COPD
asthma
fibrosis
pulmonary hypertension
pneumology
Lead sponsor: RWTH Aachen University
Sponsor class: OTHER
First posted: 2023-06-15
Enrollment: 800
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 800 patients, 4 groups

Brief summary: Dyspnea is among the most common symptoms in patients with respiratory diseases such as Asthma, chronic obstructive pulmonary disease (COPD), Fibrosis, and Pulmonary Hypertension. However, the pathophysiology and underlying mechanisms of dyspnea in patients with respiratory diseases are still poorly understood. Diaphragm dysfunction might be highly prevalent in patients with dyspnea and respiratory diseases. The association of diaphragm function and potential prognostic significance in patients with respiratory diseases has not yet been investigated.

Detailed description: The aim of the present project is to comprehensively measure respiratory muscle function and strength in patients with respiratory diseases. The investigators attempt to recruit 800 patients across four disease groups (Asthma, COPD, Fibrosis, and Pulmonary Hypertension) and the investigators intend to measure diaphragm and accessory respiratory muscle function and strength, lung function, and exercise tolerance, as well as the participants' symptom burden during one day at baseline in the investigators' lab. Thereafter, the investigators will follow up on patients by phone 3 months, 6 months, 12 months and 18 months after the investigators have seen them in the investigators' lab. Based on these results, not only the association between dyspnea exercise tolerance and diaphragm function in patients with respiratory diseases can be assessed, but also the prognostic significance of diaphragm dysfunction in these patients can be determined. As such, hospitalization and exacerbation requiring the intake of steroids will be assessed and followed up on by phone, and therefore the prognostic significance of diaphragm dysfunction in predicting hospitalization and the intake of steroids can be determined.

Eligibility criteria: Inclusion Criteria:

* patient has one of the following lung diseases: COPD, bronchial asthma, pulmonary fibrosis, pulmonary hypertension
* is 18 years or older
* is mentally and physically able to understand the study and to follow instructions
* are legally competent
* signed declaration of consent

Exclusion Criteria:

* BMI \> 35
* current or treatments or diseases in the past which could influence the evaluation of the study
* Expected lack of willingness to actively participate in study-related measures
* alcohol or drug abuse
* disc herniation/prolapse
* epilepsy
* wheelchair bound
* in custody due to an official or court order
* in a dependent relationship or employment relationship with investigating physician or one of their deputy
* emergency inpatient hospital stay within 4 weeks before study-specific examinations

Primary outcomes:
measure: Dyspnea Borg scale 1 to 10
timeFrame: 6 months recruiting
measure: Dyspnea Borg scale 1 to 10
timeFrame: follow up 3 months after recruitment
measure: Dyspnea Borg scale 1 to 10
timeFrame: follow up 6 months after recruitment
measure: Dyspnea Borg scale 1 to 10
timeFrame: follow up 12 months after recruitment
measure: Dyspnea Borg scale 1 to 10
timeFrame: follow up 18 months after recruitment
Secondary outcomes:
measure: 6 minute walking distance in m
timeFrame: 6 months recruiting
measure: Sit-to stand-test (60 seconds)
timeFrame: 6 months recruiting
measure: New York Heart Association (NYHA) classification scale 1 to 4
timeFrame: 6 months recruiting, follow up up to 18 months after last recruitment
measure: Modified Medical Research Council (MRC) Breathlessness Scale 1 to 5
timeFrame: 6 months recruiting, follow up up to 18 months after last recruitment
measure: Chronic Respiratory Questionnaire (CRQ)
timeFrame: 6 months recruiting, follow up up to 18 months after last recruitment
measure: COPD Assessment Test (CAT-Questionnaire) from 0 to 40 points.
timeFrame: 6 months recruiting, follow up up to 18 months after last recruitment
measure: Global Initiative for Asthma (GINA) classification
timeFrame: 6 months recruiting, follow up up to 18 months after last recruitment
measure: Body Plethysmography
timeFrame: 6 months recruiting
measure: Diaphragm Thickening Ratio (DTR) in percent
timeFrame: 6 months recruiting
measure: Diaphragm thickness at Total lung capacity (TLC)
timeFrame: 6 months recruiting
measure: Diaphragm thickness at functional capacity (FRC)
timeFrame: 6 months recruiting
measure: Diaphragm ultrasound sniff velocity in cm/s
timeFrame: 6 months recruiting
measure: Intercostal Muscle ultrasound thickness at Total lung capacity (TLC) in cm
timeFrame: 6 months recruiting
measure: Intercostal Muscle ultrasound thickness at functional capacity (FRC) in cm
timeFrame: 6 months recruiting
measure: Intercostal Muscle Thickening Ratio in percent
timeFrame: 6 months recruiting
measure: Maximum Inspiratory Pressure (MIP) in percent predicted
timeFrame: 6 months recruiting
measure: Maximum Expiratory Pressure (MEP) in percent predicted
timeFrame: 6 months recruiting
measure: Sniff Nasal Inspiratory Pressure (SNIP) in percent predicted
timeFrame: 6 months recruiting
measure: Blood Gas Analysis in cmH2O
timeFrame: 6 months recruiting
measure: Blood Gas Analysis in cmH2O
timeFrame: 6 months recruiting
measure: Blood Gas Analysis
timeFrame: 6 months recruiting
measure: Blood Gas Analysis in mmol/l
timeFrame: 6 months recruiting
measure: Blood Gas Analysis in (I1/s) percent
timeFrame: 6 months recruiting
measure: Electromyography (EMG)
timeFrame: 6 months recruiting
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: RWTH Aachen University Hospital
state: North Rhine-westphalia
Study officials:
affiliation: Uniklinik RWTH Aachen
name: Michael Dreher, MD
role: STUDY_DIRECTOR
affiliation: Uniklinik RWTH Aachen
name: Binaya Regmi, MD
role: STUDY_CHAIR
affiliation: Uniklinik RWTH Aachen
name: Jens Spiesshoefer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Uniklinik RWTH Aachen
name: Mustafa Elfeturi
role: STUDY_CHAIR
affiliation: Uniklinik RWTH Aachen
name: Benedikt Jörn
role: STUDY_CHAIR
affiliation: Uniklinik RWTH Aachen
name: Faniry Ratsimba
role: STUDY_CHAIR
affiliation: Uniklinik RWTH Aachen
name: Felix Wagner
role: STUDY_CHAIR
References:
citation: Daher A, Balfanz P, Aetou M, Hartmann B, Muller-Wieland D, Muller T, Marx N, Dreher M, Cornelissen CG. Clinical course of COVID-19 patients needing supplemental oxygen outside the intensive care unit. Sci Rep. 2021 Jan 26;11(1):2256. doi: 10.1038/s41598-021-81444-9.
citation: Daher A, Balfanz P, Cornelissen C, Muller A, Bergs I, Marx N, Muller-Wieland D, Hartmann B, Dreher M, Muller T. Follow up of patients with severe coronavirus disease 2019 (COVID-19): Pulmonary and extrapulmonary disease sequelae. Respir Med. 2020 Nov-Dec;174:106197. doi: 10.1016/j.rmed.2020.106197. Epub 2020 Oct 20.
citation: Balfanz P, Hartmann B, Muller-Wieland D, Kleines M, Hackl D, Kossack N, Kersten A, Cornelissen C, Muller T, Daher A, Stohr R, Bickenbach J, Marx G, Marx N, Dreher M. Early risk markers for severe clinical course and fatal outcome in German patients with COVID-19. PLoS One. 2021 Jan 29;16(1):e0246182. doi: 10.1371/journal.pone.0246182. eCollection 2021.
citation: Spiesshoefer J, Henke C, Herkenrath S, Brix T, Randerath W, Young P, Boentert M. Transdiapragmatic pressure and contractile properties of the diaphragm following magnetic stimulation. Respir Physiol Neurobiol. 2019 Aug;266:47-53. doi: 10.1016/j.resp.2019.04.011. Epub 2019 Apr 25.
citation: Spiesshoefer J, Henke C, Herkenrath S, Randerath W, Brix T, Young P, Boentert M. Assessment of Central Drive to the Diaphragm by Twitch Interpolation: Normal Values, Theoretical Considerations, and Future Directions. Respiration. 2019;98(4):283-293. doi: 10.1159/000500726. Epub 2019 Jul 26.
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.