Disease-related Fatigue Monitoring Based on Body Signals Measured on the Skin

Study Overview
=================
Brief Summary
-----------------
This study investigates the use of physiological parameters as predictors of disease-related fatigue. For that purpose, wearable devices are used to monitor cancer and post-COVID-19 patients during their stay in a rehabilitation clinic. Besides, the effectiveness of respiratory training in reducing breathlessness and improving exercise breathing patterns in patients suffering from post-COVID-19 will be explored.

Official Title
-----------------
Disease-related Fatigue Monitoring Based on Body Signals Measured on the Skin

Conditions
-----------------
Post-COVID-19 Related Fatigue, Cancer-related Fatigue

Intervention / Treatment
-----------------
* Procedure: Respiratory training


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults (≥18 years old) suffering from cancer-related/post-COVID-19 fatigue (i.e., score equal or higher than 5 on the single-item fatigue [SIF] or the Fatigue Severity Scale [FSS]) admitted to Gais rehabilitation clinic able to use a mobile phone able to wear and handle the monitoring devices Exclusion Criteria: Patients suffering from a relevant comorbidity (i.e., comorbidity resulting in significant distortion of physiological signals [e.g., moderate to severe chronic obstructive pulmonary disease or persistent atrial fibrillation]) pregnancy unable to use, wear or handle the monitoring systems

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study population comprises 40 patients, 20 suffering from cancer-related fatigue and 20 from post-COVID-19, since fatigue is a major complaint in both conditions. Since abnormal breathing patterns during exertion occur mainly in post-COVID-19 patients, only these will participate in the respiratory training intervention. Half of the post-COVID-19 patients will be the control, and the other half the intervention group.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Post-COVID-19 (respiratory training and monitoring)<br>Post-COVID-19 patients allocated to this arm get an additional respiratory training added to their conventional rehabilitation program. Patients will train twice daily for the length of their rehabilitation stay. An incentive spirometer (Voldyne 5000 R, Sherwood Medical, St. Louis, USA) will be used to complete training sessions of 15 mins each. | Procedure: Respiratory training<br>* Respiratory training will be included in the rehabilitation program of a subgroup of post-COVID-19 patients. The intervention group will train twice daily for the length of their rehabilitation stay using an incentive spirometer (Voldyne 5000 R, Sherwood Medical, St. Louis, USA). Subjects will be instructed to first completely exhale slowly. Then inspire slowly up to 70% of their vital capacity, producing a constant flow controlled via feedback from the device. This procedure will be repeated every 30 s (paced by a metronome) for 15 min. The training will be conducted twice a day, resulting in a total of 60 inspirations per day.<br>|
| No Intervention: Post-COVID-19 (control and monitoring)<br>Patients receive the same therapeutical interventions as the Post-COVID19 respiratory training arm excluding respiratory training. | |
| No Intervention: Cancer-related fatigue (monitoring)<br>Patients are treated according to the respective rehabilitation program not including respiratory training. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantification of fatigue based on self-reported fatigue by means of single item fatigue questionnaire | The single item fatigue (SIF) questionnaire is a multidimensional questionnaire developed for use in daily clinical practice. It has 5-items covering global fatigue, cognitive fatigue, emotional fatigue, physical fatigue, fatigue relief by sleep), each consisting of an 11-point likert scale (0 [no fatigue] to 10 [severe fatigue]), . Perceived fatigue was asked for the past 24 hours. | baseline | 
| Quantification of fatigue based on self-reported fatigue by means of single item fatigue questionnaire | The single item fatigue (SIF) questionnaire is a multidimensional questionnaire developed for use in daily clinical practice. It has 5-items covering global fatigue, cognitive fatigue, emotional fatigue, physical fatigue, fatigue relief by sleep), each consisting of an 11-point likert scale (0 [no fatigue] to 10 [severe fatigue]), . Perceived fatigue was asked for the past 24 hours. | after 12 weeks of rehabilitation | 
| Heart rate | Heart rate (in beats per minute) will be obtained from ECG signals monitored continuously by the eqO2+ LifeMonitor (Equivital Inc, New York, USA) | baseline | 
| Heart rate | Heart rate (in beats per minute) will be obtained from ECG signals monitored continuously by the eqO2+ LifeMonitor (Equivital Inc, New York, USA) | after 12 weeks of rehabilitation | 
| Heart rate variability | Heart rate variability (in milliseconds) will be obtained from ECG signals monitored continuously by the eqO2+ LifeMonitor (Equivital Inc, New York, USA) | baseline | 
| Heart rate variability | Heart rate variability (in milliseconds) will be obtained from ECG signals monitored continuously by the eqO2+ LifeMonitor (Equivital Inc, New York, USA) | after 12 weeks of rehabilitation | 
| Breathing rate | Breathing rate (in breaths per minute) will be obtained from breathing waveform signals monitored continuously by the eqO2+ LifeMonitor (Equivital Inc, New York, USA) | baseline | 
| Breathing rate | Breathing rate (in breaths per minute) will be obtained from breathing waveform signals monitored continuously by the eqO2+ LifeMonitor (Equivital Inc, New York, USA) | after 12 weeks of rehabilitation | 
| Physical activity intensity | The mean amplitude observed for the resultant acceleration (based on 3D acceleration measurements in g) is considered to be representative for the physical activity intensity. It will be obtained from acceleration measurements monitored continuously by the eqO2+ LifeMonitor (Equivital Inc, New York, USA) | baseline | 
| Physical activity intensity | The mean amplitude observed for the resultant acceleration (based on 3D acceleration measurements in g) is considered to be representative for the physical activity intensity. It will be obtained from acceleration measurements monitored continuously by the eqO2+ LifeMonitor (Equivital Inc, New York, USA) | after 12 weeks of rehabilitation | 
| Nocturnal blood oxygen saturation | Nocturnal blood oxygen saturation (in %) will be monitored continuously during night by Nonin Wristox2 3150 (Nonin Medical Inc., Minnesota, USA) | baseline | 
| Nocturnal blood oxygen saturation | Nocturnal blood oxygen saturation (in %) will be monitored continuously during night by Nonin Wristox2 3150 (Nonin Medical Inc., Minnesota, USA) | after 12 weeks of rehabilitation | 
| Breathing frequency at anaerobic threshold | Breathing frequency (in breaths per minute) obtained during ergospirometer test using Cortex Metalyzer 3B (Cortex Biophysik GmbH, Leipzig, Germany) during a ramp protocol (starting work load of 5 Watts, increase in work load by 12.5 Watts/min). | baseline | 
| Breathing frequency at anaerobic threshold | Breathing frequency (in breaths per minute) obtained during ergospirometer test using Cortex Metalyzer 3B (Cortex Biophysik GmbH, Leipzig, Germany) during a ramp protocol (starting work load of 5 Watts, increase in work load by 12.5 Watts/min). | after 12 weeks of rehabilitation | 
| Tidal volume at anaerobic threshold | Tidal volume (in ml) obtained during ergospirometer test using Cortex Metalyzer 3B (Cortex Biophysik GmbH, Leipzig, Germany) during a ramp protocol (starting work load of 5 Watts, increase in work load by 12.5 Watts/min). | baseline | 
| Tidal volume at anaerobic threshold | Tidal volume (in ml) obtained during ergospirometer test using Cortex Metalyzer 3B (Cortex Biophysik GmbH, Leipzig, Germany) during a ramp protocol (starting work load of 5 Watts, increase in work load by 12.5 Watts/min). | after 12 weeks of rehabilitation | 
| Respiratory exchange ratio at anaerobic threshold | Respiratory exchange ratio obtained during ergospirometer test using Cortex Metalyzer 3B (Cortex Biophysik GmbH, Leipzig, Germany) during a ramp protocol (starting work load of 5 Watts, increase in work load by 12.5 Watts/min). | baseline | 
| Respiratory exchange ratio at anaerobic threshold | Respiratory exchange ratio obtained during ergospirometer test using Cortex Metalyzer 3B (Cortex Biophysik GmbH, Leipzig, Germany) during a ramp protocol (starting work load of 5 Watts, increase in work load by 12.5 Watts/min). | after 12 weeks of rehabilitation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional assessment by means of the hand grip test | Measurement of mean strength (in kg) by pulling a dynamometer handle with maximum force for 3 seconds using the dominant hand followed by 5 seconds of relaxation. Sequence in conducted 10 times. | baseline | 
| Functional assessment by means of the hand grip test | Measurement of mean strength (in kg) by pulling a dynamometer handle with maximum force for 3 seconds using the dominant hand followed by 5 seconds of relaxation. Sequence in conducted 10 times. | after 12 weeks of rehabilitation | 
| Functional assessment by means of the time up and go test | Measures the time (in s) required to rise from a standard armchair, walk to a marker 3 m away, turn, walk back, and sit down again; assesses the dynamic balance and functional mobility. | baseline | 
| Functional assessment by means of the time up and go test | Measures the time (in s) required to rise from a standard armchair, walk to a marker 3 m away, turn, walk back, and sit down again; assesses the dynamic balance and functional mobility. | after 12 weeks of rehabilitation | 
| Functional assessment by means of the 6 min walking test | Measurement of distance covered (in m) during 6 minutes of walking. | baseline | 
| Functional assessment by means of the 6 min walking test | Measurement of distance covered (in m) during 6 minutes of walking. | after 12 weeks of rehabilitation | 
| Fatigue severity scale | Questionnaire to evaluate the impact of fatigue with a minimum value of 9 (not suffering from fatigue at all) and a maximum value of 63 (highly affected by fatigue) | baseline | 
| Fatigue severity scale | Questionnaire to evaluate the impact of fatigue with a minimum value of 9 (not suffering from fatigue at all) and a maximum value of 63 (highly affected by fatigue) | after 12 weeks of rehabilitation | 
| Health-related quality of life assessment by means of short form health survey (SF-36) | Questionnaire for the assessment of health-related quality of life (minimum value = 0, low quality of life; maximum value = 100, high quality of life) | baseline | 
| Health-related quality of life assessment by means of short form health survey (SF-36) | Questionnaire for the assessment of health-related quality of life (minimum value = 0, low quality of life; maximum value = 100, high quality of life) | after 12 weeks of rehabilitation | 
| Hospital Anxiety and Depression Scale | Questionnaire for the assessment of anxiety and depression (minimum value = 0, no signs of anxiety and depression; maximum value = 10, highest levels of anxiety and depression) | baseline | 
| Hospital Anxiety and Depression Scale | Questionnaire for the assessment of anxiety and depression (minimum value = 0, no signs of anxiety and depression; maximum value = 10, highest levels of anxiety and depression) | after 12 weeks of rehabilitation | 
| Bell Disability Scale | Questionnaire for the assessment of the patient's overall functioning (minimum value = 0, worst functioning; maximum value = 100, best functioning) | baseline | 
| Bell Disability Scale | Questionnaire for the assessment of the patient's overall functioning (minimum value = 0, worst functioning; maximum value = 100, best functioning) | after 12 weeks of rehabilitation | 
| Chronic Respiratory Disease Questionnaire | Questionnaire for the assessment of dyspnoea (in post-COVID-10 patients) consisting of 5 items covering a range of 0 (worst condition) and 8 (best condition) | baseline | 
| Chronic Respiratory Disease Questionnaire | Questionnaire for the assessment of dyspnoea (in post-COVID-10 patients) consisting of 5 items covering a range of 0 (worst condition) and 8 (best condition) | after 12 weeks of rehabilitation | 
| Edmonton Symptom Assessment System | Questionnaire for the assessment of cancer symptoms consisting of 10 items covering a range of 0 (no symptoms) and 10 (worst symptoms) | baseline | 
| Edmonton Symptom Assessment System | Questionnaire for the assessment of cancer symptoms consisting of 10 items covering a range of 0 (no symptoms) and 10 (worst symptoms) | after 12 weeks of rehabilitation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Self-reported fatigue, Fatigue questionnaires, Continous monitoring of physiological signals, Predictive model for fatigue condition, Respiratory training