Diaphragmatic Function as a Biomarker

Asthma Clinical Trial

— DFUNBIO  

Official title:

Diaphragmatic Function as a Biomarker in Patients With Respiratory Diseases

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05903001
• Other study ID #: RWTHAachenU
• Status: Recruiting
• Start date: July 1, 2023
• Est. completion date: June 30, 2025

Study information

• Verified date: November 2023
• Source: RWTH Aachen University
• Contact: Jens Spiesshoefer, MD
• Phone: 0049 2418037036
• Email: jspiesshoefer[@]ukaachen.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 800
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Asthma
• COPD
• Dyspnea
• Dyspnea; Asthmatic
• Fibrosis
• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension

Intervention

Diagnostic Test:
• Diaphragm Ultrasound
Ultrasound of the Diaphragm at the end of inspiration and expiration
• Intercostal Muscle Ultrasound
Ultrasound of the Intercostal Muscles at the end of inspiration and expiration
• Borg scale
Questionnaire for Perceived Exertion (Borg Rating of Perceived Exertion Scale)
• MRC Breathlessness Scale
The MRC Dyspnoea Scale allows the patients to indicate the extent to which their breathlessness affects their mobility.
• Respiratory Questionaire
Specialized respiratory questionnaire with different domains (Emotional Domain, Dyspnea Domain, Mastery Domain, Fatigue Domain)
• GINA classification of Asthma
Patients are classified according to the GINA classification of Asthma.
• Measurement of respiratory mouth pressure
Inspiratory and expiratory Measurement of respiratory mouth pressure
• SNIP
Measurement of Sniff Nasal Inspiratory Pressure
• 6-minute walking distance
The maximum walking distance achieved in 6 minutes
• 60 seconds sit-to-stand test
number of repetitions achieved in sitting down and standing up in 60 seconds
• Electromyography
electromyography of the muscles of respiration via superficial electrodes
• Lung Function
Measurement of lung function via body plethysmography
• CAT-Questionnaire
COPD Assessment Test (CAT)
• European Society of Cardiology (ESC)/ European Respiratory Society (ERS) risk group
Patients with pulmonary hypertension are classified according to the ESC/ERS risk group.

Locations

Country	Name	City	State
Germany	RWTH Aachen University Hospital	Aachen	North Rhine-westphalia

Sponsors (1)

Lead Sponsor	Collaborator
RWTH Aachen University

Country where clinical trial is conducted

Germany, 

References & Publications (6)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dyspnea Borg scale 1 to 10	Borg scale before and after "6 minute walking distance" test. Lower scores show fewer dyspnea, higher scores indicate more dyspnea.	6 months recruiting
Primary	Dyspnea Borg scale 1 to 10	Borg scale before and after "6 minute walking distance" test. Lower scores show fewer dyspnea, higher scores indicate more dyspnea.	follow up 3 months after recruitment
Primary	Dyspnea Borg scale 1 to 10	Borg scale before and after "6 minute walking distance" test. Lower scores show fewer dyspnea, higher scores indicate more dyspnea.	follow up 6 months after recruitment
Primary	Dyspnea Borg scale 1 to 10	Borg scale before and after "6 minute walking distance" test. Lower scores show fewer dyspnea, higher scores indicate more dyspnea.	follow up 12 months after recruitment
Primary	Dyspnea Borg scale 1 to 10	Borg scale before and after "6 minute walking distance" test. Lower scores show fewer dyspnea, higher scores indicate more dyspnea.	follow up 18 months after recruitment
Secondary	6 minute walking distance in m	Measurement of achieved walking distance in 6 minutes	6 months recruiting
Secondary	Sit-to stand-test (60 seconds)	Measurement of achieved repetitions of standing up and sitting down from an initial seated position in 60 seconds.	6 months recruiting
Secondary	New York Heart Association (NYHA) classification scale 1 to 4	Patients are linked to a NYHA degree. Lower scores show fewer dyspnea, higher scores indicate more dyspnea.	6 months recruiting, follow up up to 18 months after last recruitment
Secondary	Modified Medical Research Council (MRC) Breathlessness Scale 1 to 5	Patients are assessed and grouped according to their MRC Breathlessness Scale. Lower scores show fewer dyspnea, higher scores indicate more dyspnea.	6 months recruiting, follow up up to 18 months after last recruitment
Secondary	Chronic Respiratory Questionnaire (CRQ)	Assessments of different domains (Emotional Domain, Dyspnea Domain, Mastery Domain, Fatigue Domain) in a standardized questionnaire on a scale from 1 to 7. The scores for each question of each dimension are added together and divided by the number of completed questions in each domain. In general, higher scores mean a worse outcome and lower scores mean a better outcome.; For the dyspnea domain for example, a high score means that patients have less dyspnea, and a low score means that patients have more dyspnea.	6 months recruiting, follow up up to 18 months after last recruitment
Secondary	COPD Assessment Test (CAT-Questionnaire) from 0 to 40 points.	Patients are evaluated and placed into the corresponding groups. Lower scores show fewer dyspnea, higher scores indicate more dyspnea.	6 months recruiting, follow up up to 18 months after last recruitment
Secondary	Global Initiative for Asthma (GINA) classification	Patients are assessed and grouped as mild, moderate, or severe according to the GINA classification.	6 months recruiting, follow up up to 18 months after last recruitment
Secondary	Body Plethysmography	TLC (Total lung capacity) in percent predicted.	6 months recruiting
Secondary	Diaphragm Thickening Ratio (DTR) in percent	Via ultrasound, the diaphragm thickening ratio (DTR) was calculated as thickness at total lung capacity (TLC) divided by thickness at functional residual capacity (FRC).	6 months recruiting
Secondary	Diaphragm thickness at Total lung capacity (TLC)	Via ultrasound, the diaphragm thickness at TLC is measured at the maximum point of inspiration.	6 months recruiting
Secondary	Diaphragm thickness at functional capacity (FRC)	Via ultrasound, the diaphragm thickness at FRC is measured after a normal expiration.	6 months recruiting
Secondary	Diaphragm ultrasound sniff velocity in cm/s	Via ultrasound, the diaphragm sniff velocity was assessed during tidal breathing and following a maximum sniff.	6 months recruiting
Secondary	Intercostal Muscle ultrasound thickness at Total lung capacity (TLC) in cm	Via ultrasound, the intercostal thickness at TLC is measured at the maximum point of inspiration.	6 months recruiting
Secondary	Intercostal Muscle ultrasound thickness at functional capacity (FRC) in cm	Via ultrasound, the intercostal thickness at FRC is measured after a normal expiration.	6 months recruiting
Secondary	Intercostal Muscle Thickening Ratio in percent	Via ultrasound, the intercostal muscle thickening ratio was calculated as thickness at total lung capacity (TLC) divided by thickness at functional residual capacity (FRC).	6 months recruiting
Secondary	Maximum Inspiratory Pressure (MIP) in percent predicted	Measurement of Maximum Inspiratory Pressure	6 months recruiting
Secondary	Maximum Expiratory Pressure (MEP) in percent predicted	Measurement of Maximum Expiratory Pressure	6 months recruiting
Secondary	Sniff Nasal Inspiratory Pressure (SNIP) in percent predicted	Measurement of Sniff Nasal Inspiratory Pressure	6 months recruiting
Secondary	Blood Gas Analysis in cmH2O	oxygen partial pressure (pO2)	6 months recruiting
Secondary	Blood Gas Analysis in cmH2O	carbon dioxide partial pressure (pCO2)	6 months recruiting
Secondary	Blood Gas Analysis	pH scale	6 months recruiting
Secondary	Blood Gas Analysis in mmol/l	Base Excess	6 months recruiting
Secondary	Blood Gas Analysis in (I1/s) percent	Base Excess	6 months recruiting
Secondary	Electromyography (EMG)	Measurement of electrical activity during different breathing maneuvers (Sniff, Cough, Valsalva, Mueller) via superficial electrodes placed on the diaphragm and accessory respiratory muscles (Sternocleidomastoideus muscle, intercostal muscles).	6 months recruiting