E-monitoring of Pulmonary Function in Patients With Duchenne Muscular Dystrophy Undergoing Respiratory Rehabilitation at Home"
Phase: NA
Conditions: Duchenne Muscular Dystrophy (DMD)
Sponsor: Medical University of Gdansk

 
 
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 Protocol Version 1.1  
 
 Clinical Trial Protocol 
 
“E-monitoring of pulmonary function in patients with Duchenne Muscular Dystrophy undergoing 
respiratory rehabilitation at home”. The controlled and observational 12-months study with 
prospective cohort design.  
 
 
 Sponsor: prive 
 
Version and Date of Protocol: protocol version 1.1; dated: 01.Mar.2021 
 
The information contained in this document (particularly unpublished data) is provided only to those 
directly involved in this study (clinical study secretariat, investigators [including clinical study staff], 
study drug manager, independent ethics committee, and head of medical institution). Therefore, this 
information cannot be disclosed to third parties not involved in this study, except when consent is 
obtained from participating patients (legal representative) and when disclosure is required by 
applicable laws. 
 
“E-monitoring of PULMonary function in patients with Duchenne 
Muscular Dystrophy undergoing respiratory rehabilitation at home”. 
 
acronym :   E-PULMoDMD 
ID:  E-PULMoDMD 001/2021 
 
SIGNATURES 
I agree to conduct the study in accordance with the current protocol. 
Principal Investigator’s Name (print) ____________________________________ 
Principal Investigator’s Signature________________________________________ 
Date _______________________________________ 
 
 
 

 
 
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STATEMENT OF COMPLIANCE  
 
The trial will be carried out in accordance with International Conference on Harmonisation Good 
Clinical Practice (ICH GCP E6 (R2)).  
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the Ethic Committee (EC) for review and approval. Approval of both the protocol and the 
consent form must be obtained before any participant is enrolled. Any amendment to the protocol will 
require review and approval by the IEC before the changes are implemented to the study. In addition, 
all changes to the consent form will be IEC-approved; a determination will be made regarding whether 
a new consent needs to be obtained from participants who provided consent, using a previously approved 
consent form.  
The Principal Investigator will assure that no deviation from, or changes to the protocol will take place 
without prior agreement from sponsor,  and documented approval from the IEC, except where necessary 
to eliminate an immediate hazard(s) to the trial participants. All personnel involved in the conduct of 
this study have completed ICH GCP Training. 
 
KEY CONTACTS: NAME, TITLE, ADDRESS, TELEPHONE NUMBER INCLUDING 
PRINCIPAL INVESTIGATOR  
 
Principal Investigator:  
Sub-investigator:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table of Contents 
 

 
 
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NAME AND TITLE OF THE PERSON(S) AUTHORIZED TO SIGN THE PROTOCOL AND 
AMENDMENT(S) FOR THE SPONSOR ................................................................................... 1  
Key contacts: name, title, address, telephone number including Principal investigator  
Name(s), address(es) of the clinical laboratory(ies) or other medical and/or technical 
department(s)/institutions involved in the trial  
STATEMENT OF COMPLIANCE ............................................................................................... 2 
Table of Contents.............................................................................................................................. 3  
 
1 PROTOCOL SUMMARY ............................................................................................................... 4  
1.1 Synopsis ..................................................................................................................... 4  
1.2 Abbreviations ............................................................................................................. 4  
 
2 INTRODUCTION .......................................................................................................................... 5 
  
3 AIMS, OBJECTIVES AND ENDPOINTS .................................................................................. 6  
 
4 STUDY DESIGN ........................................................................................................................... 6  
4.1 Overall Design ......................................................................................................... 6 
4.2 Investigate procedures  .......................................................................................... 7  
 
5 STUDY POPULATION ................................................................................................................. 8  
5.1. Inclusion Criteria........................................................................................ 8 
5.2. Exclusion Criteria................................................................................................... 8  
 
6 PARTICIPANT RECRUITMENT PROCESS ............................................................................ 8 
6.1 Recruitment Setting ................................................................................................ 9  
6.2 Screening ................................................................................................................. 9  
6.3 Informed Consent, Trial Records ........................................................................ 9 
6.3.1 Consent Process .................................................................................... 9  
 
7 STUDY INTERVENTION .............................................................................................................10  
7.1  Description of all Trial Periods ..................................................................................... 10  
7.1.1 Enrolment visit.................................................................... 10 
7.2.2 Follow-up visit and end-point visit ............................................................. 14 
8 STATISTICAL CONSIDERATIONS ............................................................................. 15 
8.1. Sample size estimation ........................................................................................ 15 
9 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS....... 15 
9.1 Ethics…………………………………………………………………………………..15 
9.2 Publication………………………………………………………………………………….15 
9.3 Conflict of Interest Policy …………………………………………………………………..16 
8. COVID-19 (SARS-COV-2 INFECTION) SAFETY MEASURES ……………………….16 
 
 
1 PROTOCOL SUMMARY 
 1.1 SYNOPSIS 

 
 
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Title: 
“E-monitoring of pulmonary function in patients with Duchenne Muscular Dystrophy undergoing 
respiratory rehabilitation at home”. The controlled and observational 12-months study with 
prospective cohort design. 
Short title: E-monitoring of pulmonary function in Patients with Duchenne Muscular Dystrophy 
(DMD). 
*Acronym: E-PULMoDMD 
 
Abbreviations:  
DMD, Duchenne muscular dystrophy 
BMI, body mass index  
BS, Brooke scale 
VS, Vignos scale 
FVC, forced vital capacity 
FEV1, forced expiratory volume in 1 second  
PEF, peak expiratory flow 
MEP, maximal expiratory pressure  
MIP, Maximal inspiratory pressure 
PUL, Performance of Upper  Limb   
 
Study Description: 
The controlled and observational 12-months study with prospective cohort design and 
longitudinal data collection performs in paediatric patients with established diagnosis of DMD, at 
the Department of Allergy and Pulmonology Medical University of Gdansk, Poland.  
The study includes 200 patients with DMD diagnosis confirmed by genetic testing, 7-17 years old (7 
≥and <18) at the study entry with the routine standardized a follow-up of up to 4 weeks, 12 weeks, 
24 weeks and  12 months.  
The study size is estimated at 200, with a dropout rate after the 12-month follow-up period being 
ca. 10% (N=180). The study consists of 4 arms: 3 actives and 1 control (each arm of n=50 participants; 
with dropout rate after 12 months ca.10%, n=45). 
Duration of the project March 2021 - March 2025. 
 
2 INTRODUCTION 
 

 
 
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Duchenne muscular dystrophy (DMD) is the most common and most severe muscular dystrophy 
recognized in childhood. DMD is a genetically determined, progressive, irreversible disease in which 
dystrophin dysfunction in skeletal and multiple organ muscles is fatal before the age of 20 years. 
Nowadays, multi-specialist care has resulted in an increase in patient survival by up to 10-25 years. 
However, the respiratory muscle failure is the most common cause of death [1,2], so assessment and 
treatment of respiratory system is one of the most important problems for DMD patients. 
In the first years of life, the respiratory system of children with DMD is efficient and does not differ 
from that of healthy peers. From the age of 7 years, the parameters of lung function no longer increase, 
and between the ages of 10 to 12 years, when the child loses the ability to walk independently, the 
lung function rapidly deteriorates [3]. 
The basic tasks include the initiation of early monitoring of respiratory system functions. It is 
recommended that measurement of lung function is started from the age of 5 years [1,2,4]. Taking the 
measurement at such an early age is aimed at familiarizing and teaching the child about this type of 
systematic examination and determining the individual maximum parameters of lung function in each 
child. Thanks to systematic measurements, it is possible to detect any sharp deterioration as well as 
the moment when the decreasing lung function requires respiratory support, so-called non-invasive 
ventilation (NIV). 
According to the standards, lung function is assessed by spirometry, which should be performed at 
least once a year, at least every 6 months after losing independent walking, and every 3 months after 
starting non-invasive ventilation [1,2]. 
The spirometry test assesses forced vital capacity (FVC), which is considered a marker of disease 
progression. An FVC value below 2.1 L is a rationale to start supporting the cough reflex, and below 1 L 
is an indication to start respiratory support, i.e. NIV [5,6,7,8,9,10]. 
Implementation of the above-mentioned tests often encounters difficulties which increase when the 
child loses independent walking. Additionally, during the COVID pandemic, which runs from March 
2020 in Poland, spirometry was included in the procedures generating aerosols, i.e. high risk of SARS-
CoV-2 virus transmission. Therefore, it has become necessary to look for other methods of measuring 
and monitoring lung function in children with DMD. 
Because a major component of respiratory dysfunction seems to be decline of inspiratory muscle 
weakness [3,6] therefore also respiratory training and rehabilitation is recommended as one of the key 
elements of DMD patient care [1,3]. 
The time of the SARS-CoV-2 pandemic also makes it necessary to look for rehabilitation methods at 
home. The assumption of the exercises is the possibility of performing them independently, at home, 
without the assistance of a physiotherapist, and without the use of additional equipment. 
 
Summary: Pulmonary rehabilitation is one of the key issues in DMD patient management. The 
combination of systematic home lung function measurement with home respiratory rehabilitation is 
an innovative project. It is a non-invasive test, and the measurement is intended to improve the quality 
of life of DMD patients. 
3. AIMS, OBJECTIVE 
 

 
 
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Objectives: 
The primary objective of this study is to evaluate whether using home electronical device to monitoring 
pulmonary function and/or home telerehabilitation can slow the rate of progression pulmonary 
function  in males with DMD compared to control group without using home e-device and 
telerehabilitation. 
 
The second aim of this study is: 
to investigate whether it is possible to monitor pulmonary function at home using an electronical 
spirometry system called AioCare  in boys with DMD.  
to assess the acceptance of telerehabilitation of respiratory system in this group of patients. 
to assess the acceptance of electronical home monitoring of respiratory system in this group of 
patients. 
to assessment of the quality of life of patients subjected to electronic monitoring and pulmonary 
rehabilitation vs. not subjected (validated questionnaires) 
 
4. STUDY DESIGN 
 
4.1 Overall design 
The study consists of 4 arms: 3 actives and 1 control (figure 1).  
ARM 1: Patients in arm 1 use electronical home device to measurements pulmonary function,  
ARM 2: Patients in arm 2 use  electronical home device to measurements pulmonary function, and 
perform telerehabilitation,  
ARM 3: Patients in arm 3 perform telerehabilitation  
CONTROL GROUP: Patients without home e-monitoring pulmonary function and telerehabilitation.  
Enrolment of a patient to one of four groups (active or control) takes place after enrolment visit in 
random order.  
As a part of the clinical trial, diagnostic examinations evaluating progression of the disease, pulmonary 
function tests will be performed periodically. The compliance, efficacy, accomplishment in all patients 
will be monitored by questionnaire during follow -up visits. The problems with investigate procedures 
(e-spirometry, telerehabilitation) and patients' personal well-being will be controlled using 
telemedicine technologies. Additional visits in the research center will be provided if any adverse 
events occur. This model will be continued for 12 months from the enrolment. After 4 weeks the first 
home  e-monitoring pulmonary function and respiratory telerehabilitation efficiency analysis will be 
performed.  
The study may be continued for 12 months or in case of negative impact of the intervention on 
patients' health and well-being, terminated with further patients monitoring 

 
 
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Figure 1. Study design 
 
4.2 Investigate procedures  
The presented project evaluates the measurement of lung function at home using an individual 
electronic spirometer called an AioCare [11] and home respiratory telerehabilitation. 
4.2.1 Home e-spirometry  
Home e-spirometry will be performed by AioCare system ((AioCare® spirometers, Healthup, Poland) 
[11].  The AioCare spirometer is a small, convenient device that can be used anywhere. The device 
enables systematic non-invasive monitoring of lung parameters (including FVC measurement) at home 
in children over 5 years of age. The child inhales and exhales forcefully through a mouthpiece with 
antibacterial and antiviral filters. The test results are sent from the AioCare spirometer via the AioCare 
application for iOS and Android (as used by all current smartphones). Communication between the 
AioCare spirometer and the application takes place via a Bluetooth 4.0 (BT LE) connection. The 
spirometry results are available to the practitioner in real time in the AIOCARE Doctor panel. 
 
4.2.2 Home respiratory telerehabilitation 
A module with exercises for training respiratory muscles, will be included in an additional smartphone 
application.  
It will be a series of 4 exercises aimed at strengthening respiratory muscles, to be performed after the 
spirometry test; twice every day. 
Participants will perform forced exhalation exercises with a relaxed epiglottis, exercises to improve the 
mechanics of the chest and the mobility of the shoulder girdle. The duration of the exercises is 
approximately 7 minutes. The exercise program will be recorded in the form of an instructional video.  
           
              
          
       
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4. STUDY POPULATION 
 
4.1 Inclusion criteria 
The study includes patients with signed informed consent, i.e. those who agree to participate in a 
clinical study and meet the inclusion criteria. The children will be enrolled in the study after their legal 
guardians read, agree to, and sign the informed consent form. All children older than 12 as well as 
adolescents will be enrolled in the study after signing the inform consent, as well. The subjects will be 
assesses for inclusion and exclusion criteria on first study visit after signing the informed consent.  
Inclusion criteria are as follows: (1) male with DMD diagnosis based on current guidelines, the presence 
of typical clinical symptoms, genetic testing, and/or muscle biopsy results [1]. (2) male  ≥7 years and 
<18 years of age at time of enrollment in the study; (3) ability to perform spirometry; (4) do not use 
breathing support; and (5) stated willingness to comply with all study procedures and availability for 
the duration of the study. 
 
4.2 Exclusion criteria 
Autism 
  
6. PARTICIPANT RECRUITMENT PROCESS 
 
6.1 Recruitment Setting 
 
In order to support the recruitment of patients the following actions will be undertaken: 
I. Public study announcement and participant invitation 
• 
preparation and distribution of the informational advertisements, fliers, and brochures 
• 
preparation of the study website containing information for patients and their families 
• 
establishment o  contact an  cooperation  ith patient’s organizations thro gho t the co ntr  
(such as "Parent Project DMD") 
• 
other actions as outlined in the Recruitment strategies 
 
II. Contacting potential participants 
• 
answer any preliminary questions or doubts over a phone or internet communicator as 
suitable for the patient or guardian, point to the study website  
 
 
6.2 Screening  
 
 Screening will take place at the study Site. Medical workup will include a visit to the nurse 
(measurements), interview and medical examination. Education on the study protocol. Signing the 
study consent form.  

 
 
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Every subject after giving the consent will be given one, unique screening number. The number will be 
used for identification of the subject for all procedures. In case a subject is screened more than once 
he will always have the same screening number.  
The investigator agrees to complete a participant identification and enrolment log to permit easy 
identification of each participant during and after the study. 
  
6.3 Informed Consent, Trial Records  
 
The study will be conducted in accordance with the protocol, with established ethical principles in the 
Helsinki Declaration, in line with the harmonized ICH Guidelines for Good Clinical Practice (GCP), 
Relevant BI Standard Operating Procedures (SOP), and other relevant recipes. Investigators and plant 
employees must follow these rules. Deviation from protocol, rules of ICH GCP or applicable law that 
will be considered "protocol deviation".  
Standard medical care (prophylactic, diagnostic and treatment procedures) still remains responsibility 
of the patient's doctor and participants are required to attend neurologist, rehabilitation specialist and 
other specialist if indicated for supervision of musculoskeletal function in accordance with current 
DMD treatment guidelines.  
 he Investigator  ill obtain the  ritten in orme  consent  rom the s bject’s parent(s) or g ar ian(s) 
prior to any study-specific procedures.  
 ach s bject’s parent(s) or g ar ian(s)  ill receive an explanation o  the nat re an  p rposes o  the 
study from the Investigator or designee.  
Time will be given to the parent(s)/guardian(s) to ask questions and make their decision on whether 
they would like for their child to participate.  
The Investigator or designee will ensure the study is appropriate for the subject.  
Subjects are considered to be enrolled in the study at the time written informed consent is obtained.  
 
 
6.3.1 Consent Process  
 
In orme  consent is a process that is initiate  prior to the in ivi  al’s agreeing to participate in the 
study and continues throughout the in ivi  al’s st    participation. Consent  orms  ill be I C-
approve   an  the s bject’s parent(s) or g ar ian(s) an  participant  ill be as e  to rea  an  revie  
the document. The investigator will explain the research study and answer any questions that may 
arise.   verbal explanation  ill be provi e  in terms s ite  to the participant’s comprehension o  the 
purposes, procedures, and potential risks of the study and of their rights as research participants. The 
participants should have the opportunity to discuss the study with their family or surrogates or think 
about it prior to agreeing to participate. The informed consent process will be conducted and 
documented in the source document (including the date), and the form signed, before the participant 
undergoes any study-specific procedures. The rights and welfare of the participants will be protected 
by emphasizing to them that the quality of their medical care will not be adversely affected if they 
decline to participate in this study.  
 he s bject’s parent(s) or guardian(s) will be asked if s/he understands that the study is for research 
purposes only and that it may not provide any benefit to the subject and that the subject is free to 
withdraw from the study at any time without prejudice. Each s bject’s parent(s) or g ar ian(s)  ill be 

 
 
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required to sign a study ICF before any procedures are performed for the study; both parents or 
guardians will sign the ICF in jurisdictions where this is required.  
If applicable, the assent of the child himself will also be obtained, if possible, in writing per individual 
where a child is intellectually capable of assenting (and in accordance with local regulations: according 
to Art. 25 (in connection with Article 37h (1) (1) of the PF), if a minor is 16 or under 16 and is able to 
expressly express his opinion on his participation in the experiment, his consent is also required. At 
any time, the researcher is obliged to take into account the wishes of the minor (able to express an 
opinion) regarding the refusal to participate in the study or withdrawal from the study.), and with the 
permission of the parent(s)/guardian(s).  
The Investigator or designee will obtain ICF in accordance with the principles outlined in the current 
version of the Declaration of Helsinki. Informed Consent Forms must be dated and signed by the 
Investigator or  esignee an  the s bject’s legal representative(s) an  the original signe  consent  orm 
m st be  ept b  the Investigator in the st    s bject’s  ile.  
“Legal representative” means an individual whom a judicial or other body authorized under applicable 
la  to consent on behal  o  a prospective st    s bject to the s bject’s participation in the 
procedure(s) involved in the research. The Study Monitor will ensure that the ICF has been signed by 
the s bject’s legal representative(s).  he st    s bject’s legal representative(s)  ill receive a cop  o  
the signed consent form. Consent will be a continuing process; investigator will foster a continuous 
dialogue with participants and inform them of anything new related to the trial. 
 
  
 
7. STUDY INTERVENTION  
 
7.1 Description of all Trial Periods  
7.1.1.Enrollment  visit  
During the enrollment visit, medical history data and clinical symptoms of the respiratory system will 
be collected from an interview. A physical examination, Vignos scale (VS) assessment, Brooke scale 
(BS) assessment, and spirometry (Jaeger, Germany), Respiratory muscle assessment (Maximal 
inspiratory pressure -MIP, and Maximal expiratory pressure- MEP), Assessment of the muscles of the 
upper limb (Performance of Upper  Limb -PUL),  Maximal grip strength (dynamometry) will be 
performed in all participants.  
Participants on arm 1 and 2 will receive an electronic individual spirometer (AioCare) with a 2-h 
training session how to use it. Each participant was then asked to perform on their own three 
correct spirometry measurements twice daily (morning and evening) at home.   
Participants from arm 2 and 3 will receive a 1-hour training with respiratory rehabilitation and link 
to video presentation with respiratory rehabilitation exercises to home daily using. 
 
• 
Functional status  
The functional status of the participants was assessed by the Vignos scale (VS). The scores on the VS 
range from 1 to 10 (1 - the subject can walk and climb stairs without assistance, 10 - the subject is 

 
 
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confined to a bed). The VS allows staging of the disease and focuses on functional ambulatory activities. 
This is the main scale used for characterizing the progression of disease [12]. Upper limb functional 
status was assessed with the 6-point Brooke scale (BS) (1 - the subject can abduct their arms in a full 
circle until they touch above their head, 6 - the subject has no useful function of the hands) [13]. 
• 
Respiratory muscle assessment 
MicroRPM- Maximal respiratory pressure and reflecting respiratory muscle strength was 
measured   using a calibrated portable hand-held mouth pressure meter  (MicroRPM; Micro Medical 
Ltd., Rochester, England) in a sitting position. To measure maximal expiratory pressure (MEP), subjects 
performed maximal expiratory effort after maximal inspiration. Maximal inspiratory pressure (MIP) 
was measured by exerting maximal inspiratory effort after maximal expiration. To measure these 
pressures, effort was maintained for at least 1 second. The highest positive MEP value and the lowest 
negative MIP value in three or more attempts were chosen. We calculated percent predicted MEP 
(MEP%) and MIP (MIP%) values according to the formulas: MEP% MEP*100 / (7·619 + ( 7·806 * age ) 
+ (0·004 * height * weight));  MIP%-MIP*100 / ( –27·020 – ( 4·132 * age ) – (0·003 * height * weight)) 
• 
Pulmonary function tests 
Lung function by spirometry using the calibrated, computerized spirometer Pneumo Screen (Jaeger, 
Germany) will be performed according to the European Respiratory Society and American Thoracic 
Society recommendations, by a certificated, experienced pediatric pulmonologist [6,14]. The highest 
value of forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), peak expiratory 
flow (PEF) expressed as liters (L) and liters per minute (L/min) accordingly, and percent predicted 
value (%pv) from correct acceptable attempts will be evaluated. The results will be compared with 
results from home electronical spirometry. 
• 
Assessment of the muscles of the upper limb  
Performance of Upper  Limb (PUL )-  a functional scale specifically designed for assessing upper limb 
function in Duchenne muscular dystrophy (DMD). It includes three domains (shoulder, mid- and distal), 
each including items exploring activities easily related to activities of daily living that both patients and 
clinicians identified as relevant. Each dimension (shoulder, mid, distal) can be scored separately. In the 
PUL 2.0 there is a maximum score of 12 for the shoulder level, 17 for the mid-level, and 13 for the 
distal level. A total score of 42 can be achieved by adding the three level scores [15]. 
Dynamometry – Maximal grip strength was measured using dynamometer FT-5988 – N1 (Spais, 
Poland) – very sensitive electronic device developed to measure grip in very weak patients, the device 
can be also applied in assessment of healthy subjects. The dynamometer measures forces from 0 to 
1000N with a resolution of 0,02N. All measurements were conducted by the same experienced and 
trained evaluators. Grip strength was measured on the dominant side with a high precision 
dynamometer. All tests were performed with patients seated on a chair or in their wheelchair facing a 
table with the forearm placed on the table on the waist level. Trials were carried out with strong verbal 
encouragement asking the patients to provide maximal voluntary isometric contractions for 3 s. A rest 
period of about 30 s was respected between the trials. Patients were asked to perform three trials. 
The mean value was calculated from three valid trials.  
• 
Telerehabilitation – respiratory exercises 

 
 
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Participants from arm 2,and 3 will received a 1-hour training with respiratory rehabilitation and link to 
video presentation with respiratory rehabilitation exercises to home daily using. 
The video with the instruction of respiratory exercises: positive inspiratory pressure, glossopharyngeal 
breathing and positive expiratory pressure was showed to parents and patients at the Conference 
during the Physical Therapy panel. Participants were asked to perform the exercises themselves at 
home  itho t ph siotherapists’ assistance. Patients  ere enco rage  to train ever   a   three times 
a day. On the video patients received following instructions:  
1. Breath stacking (positive inspiratory pressure): patients were asked to take maximal inhale, then 
without exhaling, to take another 1-3 inhales, and hold for 5 seconds. Boys were instructed to repeat 
the exercise 5 times. The aim of the exercise was to increase lung volume. The same exercise was 
presented with the use of balloon – inflated balloon – patients were instructed to inhale the air from 
balloon, without exhaling and try to hold as much air in the lungs as possible – hold for 5 seconds and 
repeat for 5 times.  
2. Glossopharyngeal breathing – patients were instructed to push series of small volumes of air by 
tong e an  phar nx into the l ngs b  sa ing ‘cat’ in Polish - patients were encouraged to repeat the 
exercise for 5 times. 
3. Positive expiratory pressure – inflating the balloon – patients were instructed to inflate the balloon 
by inhaling by nose and exhaling by mouth – the exercise should be repeated for 3 times. Caregivers 
were encouraged to try different types of balloons to find optimal elasticity of material (optimal 
resistance). 
 
The 
video 
is 
available 
in 
the 
internet 
https://www.youtube.com/watch?v=AEaxOsuJimU&feature=youtu.be. 
 
7.1.2 Follow-up visit 
Visit 1  
• 
Feasibility home e- monitoring pulmonary function survey  
Participants from arm 1 and 2 during visit 1 (after 4 weeks training home using e-device), will be 
completed a survey that included questions about home spirometry (compliance, satisfaction, and 
problems with the use of the electronical spirometer at home).  Patients were asked to express their 
general satisfaction and the intelligibility of the instructions from the AioCare home spirometry on a 
5-point scale,  here “ ” meant the  orst an  “ ” meant the best score. Participants  ho  ere not 
able to perform spirometric measurements regularly were also asked the reason why and what would 
help them to take measurements more regularly. The last question concerned the benefits of home 
spirometry (table 1).  
Table 1. Survey of satisfaction and possibility of home e-monitoring pulmonary function in DMD 
patients.  
Home AioCare e-spirometry  
1. Mark on the scale how you rate the monitoring of lung function with the home spirometer. 
1 
2 
3 
4 
5 

 
 
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the worst                                                                                                                  the best 
2. Mark on the scale how you assess the comprehensibility of the instructions received for 
self-measurements of spirometry. 
1 
2 
3 
4 
5 
the worst                                                                                                                  the best 
3. If you have not been able to perform spirometric measurements regularly, what was the 
most common reason for this? 
- 
Correct blowing into the spirometer is too difficult for me 
- 
I don't have time to blow into the spirometer 
- 
I have no motivation for this assessment 
- 
I feel unwell 
- 
I forget to take the measurements 
- 
other reasons: ..................................................................................................... 
4. What would be helpful for you to take measurements every day?  
- 
reminder sent via SMS 
- 
weekly online appointment with your doctor 
- 
weekly report of my results with interpretation 
- 
I am not able to take measurements everyday 
- 
other: ..................................................................................................... 
5. Do you think that you benefit from home spirometry measurements? 
YES   NO 
6. I  ‘Y  ’  the bene its are: 
- 
I can breathe easier 
- 
I can clear my lungs easier 
- 
I feel more confident 
- 
I like to use new electronic spirometer 
- 
I will not be afraid of performing spirometry in the hospital 
- 
other: ..................................................................................................... 
 
• 
Feasibility telerehabilitation  

 
 
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The structured questionnaire consisted of questions that covered several areas: (1) respiratory 
exercises; (2) additional information required with respect to exercises and home-based program; (3) 
satisfaction from program. 
Respiratory exercises: The participants were asked: (a) whether the exercises were performed (yes/no, 
alone/with assistance), (b) possibility to implement this treatment to daily routine and about how 
often the exercises could be performed from patients perspective (3 times daily/ 1-2daily/ few times 
a week/not possible), (c) difficulty of the exercises (all exercises possible to perform/ possible to 
perform after practicing/some exercises too difficult, all exercises too difficult).  
Additional information: The caregivers were invited to leave an e-mail contact in case they needed 
expanded individual consultation or training.  
Satisfaction from program: Respondents were also asked to assess general satisfaction, 
appropriateness of the exercises and intelligibility in six points scale, where 0 meant the worse and 5 
meant the best score. 
 
Visit 2 and Visit 3 
All patients will be followed up after 3, and 6  months from visit 1. Lung function testing, will be  
recorded and assessed at this visit.  
Lung function by spirometry using the calibrated, computerized spirometer Pneumo Screen (Jaeger, 
Germany) will be performed according to the European Respiratory Society and American Thoracic 
Society recommendations, by a certificated, experienced pediatric pulmonologist [6,14]. The highest 
value of forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), peak expiratory flow 
(PEF) expressed as liters (L) and liters per minute (L/min) accordingly, and percent predicted value 
(%pv) from correct acceptable attempts will be evaluated. The results will be compared with results 
from home electronical spirometry. 
 
End -point visit  
• 
During the end-point  visit (after 12 months), medical history data, clinical symptoms of the 
respiratory system will be collected from an interview. A physical examination, Vignos scale 
(VS) assessment, Brooke scale (BS) assessment, and spirometry (Jaeger, Germany), Respiratory 
muscle assessment (Maximal inspiratory pressure -MIP, and Maximal expiratory pressure- 
MEP), Assessment of the muscles of the upper limb (Performance of Upper  Limb -PUL),  
Maximal grip strength (dynamometry) will be performed in all participants.  
 
 
8. STATISTICAL CONSIDERATIONS  
Sample size estimation 
Estimation of the sample size was based on the expected differences of the FVC between the groups 
with and without intervention. In the reference studies annual decline of FVC is varied between 6-11% 
(mean 8.5%). Assuming that telerehabilitation with using mobile spirometry can decrease this decline 
to 6% per year with standard deviation of 3% we estimated sample size for the study arms. Taking into 
account 80% power of the test, 5% significant level, the number of the subjects in the arm 1 (AioCare 

 
 
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device spirometry + telerehabilitation of the respiratory system) and control group equals 46 per 
group; finally 50 subjects per group were established. The same number of subjects were determined 
in the rest arms of the study (arm 2 – only mobile spirometry and arm 3 – only telerehabilitation). 
Statistical Analysis 
The results of the statistical analysis will be expresse  as mean ± stan ar   eviation ( D) or me ian 
and interquartile range (IQR). The comparison analysis of the results will obtaine from ambulatory 
spirometry and results from home spirometry using the AioCare spirometer will be performed using 
paired, parametric Student t-test, or non-parametric Wilcoxon signed-rank test (depending on 
whether compared values were normally distributed, which was evaluated using the Shapiro–Wilk 
test) with a significance level of p = 0.05. 
The relationship between the compliance of spirometry parameters, such as number of days with 
performed spirometry tests and clinical parameters (age, BMI, AS, VS, BS) and spirometry results 
(FEV1%pv or FVC%pv), will be evaluated using linear regression analysis. The goodness of fit of the 
mo el  base  on   ai e’s in ormation criterion ( IC)   ill compare between the four models. The 
number of independent variables will reduce using backward, stepwise regression models. This 
method allows for a decrease in the variables from the model that do not contribute to the explanation 
of the variability of dependent variables, which reduces the complexity of the model (which was 
necessary due to the limited sample size). The correlation between continuous variables will be 
evaluated using Pearson correlation coefficients.  
 
 
9. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS  
 
9.1  Ethics  
The study will be conducted in accordance with the law, local regulations, principles of GCP and 
Declaration of Helsinki.  
Before the start of the study, the protocol, ICF, and any other appropriate documents will be submitted 
to the IEC for approval. The Investigator will keep the IEC informed regarding the status of the study. 
No changes will be made without IEC approval, except when required to eliminate immediate hazards 
to the subjects.  
The Investigator will submit to the IEC the following:  
1. Information on serious or unexpected AEs, as soon as possible  
2. Periodic reports on the progress of the study  
3. Final Study Summary upon study completion or closure.  
Notification of the end of the trial will be sent to the IEC within 30 days after completion of the study 
close-out visit. The IEC will be notified within 15 days in case the study is ended prematurely.  
 
9.2  Publication  

 
 
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The results will be disseminated through manuscript publications in high impact scientific journals, 
international workshops and presentations at scientific meetings and parents' forums.  
 
9.3 Conflict of Interest Policy  
There is no conflict of interest. 
 
10. COVID-19 (SARS-COV-2 INFECTION) SAFETY MEASURES  
 
COVID-19 PREPARADNESS AND PREVENTION  
Based on the current data and understanding of both DMD and COVID-19 (Coronavirus Disease 2019) 
patients suffering DMD are potentially at higher risk of severe course of COVID-19. The following 
measures are to minimalize SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2 – the virus 
responsible for COVID-19) infection risk to other patients and their guardians, as well as personnel. 
One should be aware that total risk elimination in real life setting is nearly impossible. Two-fold 
measures will be implemented – patient specific and infrastructural.  
As of now three main routes of transmission of SARS-CoV-2 are confirmed: respiratory droplets, 
aerosols and contact transmission. PFTs are non-invasive tests that are commonly performed in 
routine assessment and follow-up of patients with DMD. Most of the procedures planned by the study 
protocol (patient history and examination etc.) pose low to moderate risk of SARS-CoV-2 transfer and 
allow for both personnel and patient to were personal protective equipment (PPE). However, PFTs 
(pulmonary function tests, e.c. spirometry) may generate aerosols and require sharing common room 
and surfaces during forced expiration with the patient unable to wear a face mask. Thus, PFTs is 
considered high risk procedure. To address this risk the following measures will be implemented.  
Patient specific recommendations  
1. Every patient and guardian 1–2 day before each visit will be required to complete (by telephone or 
email or PRO-eCRF software)  
a. epidemiological history  
b. COVID-19 specific symptoms history  
c. Local (regional) epidemiological status as reported by Polish Ministry of Health  
I  a. positive or b. positive or c. “Re ” – COVID-19 PCR test at place of residence.  
If PCR test doubtful or positive – visit postponed by 2 weeks, repeat a. to c. + PCR test. 
2. Required from every patient and guardian accompanying during visit  
a. Mask covering mouth and nose at all times  
b. Hand disinfection before and after each procedure (on entering and leaving the room)  
Study center, equipment and personnel (infrastructural preparedness)  
I. Standard risk procedures (all except PFTs)  

 
 
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1. Personnel  
a. Mask covering mouth and nose at all times  
b. Hand disinfection after each patient  
2. Room and equipment  
a. Equipment and surfaces disinfection before each patient  
II. High risk procedures (PFTs)  
3. Personnel  
a. Full set PPE: Gown, respirator (FPP2 or N95), full-face shield and disposable gloves  
b. Hand disinfection after each patient  
4. Room and equipment – Spirometry lab  
a. Forced high efficiency room ventilation / air purifier  
b. Post-test cleaning and disinfection procedures of the equipment and the testing room  
c. Individual Antiviral/Antibacterial Filters for the equipment i.e. spirometer (high viral and bacterial 
filtration efficiency (99.999%), low resistance to airflow, minimal dead space)  
The choice of specific types and brands of PPE, filters, disinfectants and air purification methods at the 
discretion and in accordance with recommendations, standards and practices of the specific study 
center.  
This measures were prepared in compliance with Recommendation from ERS Group 9.1 (Respiratory 
function technologists/Scientists) Lung function testing during COVID-19 pandemic and beyond 
(https://ers.app.box.com/s/ zs1uu88wy51monr0ewd990itoz4tsn2h) and ERS COVID-19 resource 
centre 
(https://www.ersnet.org/the-society/ 
news/novel-coronavirus-outbreak--update-and-
information-for- healthcare-professionals); Novel Coronavirus (COVID-19): The ATS Response 
(https://www.thoracic.org/professionals/clinical-resources/ 
disease-related-resources/novel-
coronavirus.php) 
 
 
14 EFERENCES 
 
 
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Hadjiyannakis, S.; Olson, A.K.; et al. Diagnosis and management of Duchenne muscular 
dystrophy, part 2: Respiratory, cardiac, bone health, and orthopaedic management. Lancet 
Neurol. 2018, 17, 347–361.  

 
 
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