Comparison of Blended Care Outpatient Neurorehabilitation With Traditional Outpatient Neurorehabilitation, a Crossover Pilot Study
Phase: NA
Conditions: Stroke, Intracerebral Haemorrhage, Brain Trauma
Sponsor: Luzerner Kantonsspital

Comparison of blended care outpatient neurorehabilitation with traditional 
outpatient neurorehabilitation, a crossover pilot study 
Study Type: 
Risk Categorisation: 
Study Registration: 
Other Clinical Trial according to ClinO, Chapter 4 
A 
1.Intended registry: clinicaltrials.gov 
2.Registration number from the FOPH portal HumRes ( follows 
Approval) 
Dr.  med. Noortje Maaijwee, Luzerner Kantonsspital, Spitalstrasse, 
6003 Luzern 
Dr.  med. Noortje Maaijwee, Luzerner Kantonsspital, Spitalstrasse, 
6003 Luzern 
Traditional outpatient neurorehabilitation (Physiotherapy, 
occupational therapy, speech therapy and 
neuropsychology at the clinic), blended with telerehabilitation 
(Home setting) 
Sponsor: 
Principal Investigator 
Investigated Intervention: 
Protocol ID 
Comparison of blended care out 
Version and Date 
Version 2.1 (24.12.2025) 
CONFIDENTIALITY STATEMENT 
The information contained in this document is confidential and the property of the principal 
investigator. The information may not - in full or in part - be transmitted, reproduced, published, 
or disclosed to others than the applicable Competent Ethics Committee and Regulatory Authority 
without prior written authorisation from the principal investigator except to the extent necessary 
to obtain informed consent from those who will participate in the study. 
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PROTOCOL SIGNATURE FORM 
Study Title 
Study ID 
Comparison of blended care outpatient neurorehabilitation 
with traditional outpatient neurorehabilitation, a crossover 
pilot study 
Comparison of blended care out 
The Sponsor- Investigator has approved the protocol version 2.1 (dated 24.12.2025) and confirm 
hereby to conduct the study according to the protocol, current version of the World Medical 
Association Declaration of Helsinki[1], the HRA[2] and ICH-GCP guidelines as well as the local 
legally applicable requirements. 
Sponsor: 
Name: Dr. med. Noortje Maaijwee 
Date: 
24.12.2025 
Signat e: 
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TABLE OF CONTENTS 
TABLE OF CONTENTS 
3 
GLOSSARY OF ABBREVATIONS 
4 
1 STUDY SYNOPSIS 
5 
2 BACKGROUND AND RATIONALE 
7 
3 STUDY OBJECTIVES AND DESIGN 
8 
3.1 Hypothesis and primary objective 
8 
3.2 Primary and secondary endpoints 
8 
3.3 Study design 
9 
3.4. Study intervention 
9 
4 STUDY POPULATION AND STUDY PROCEDURES 
9 
4.1 Inclusion and exclusion criteria, justification of study population 
9 
4.2 Recruitment, screening and informed consent procedure 
10 
4.3 Study procedures 
11 
4.4 Withdrawal and discontinuation 
11 
5 STATISTICS AND METHODOLOGY 
11 
5.1. Statistical analysis plan and sample size calculation 
11 
5.2. Handling of missing data and drop-outs 
12 
6 REGULATORY ASPECTS AND SAFETY 
12 
6.1 Local regulations / Declaration of Helsinki 
12 
6.2 (Serious) Adverse Events and notification of safety and protective measures 
122 
6.3 (Periodic) safety reporting 
13 
6.4 Amendments 
13 
6.5 Notification and reporting upon completion, discontinuation or interruption of the 
study 
14 
6.6 Insurance 
14 
7 FURTHER ASPECTS 
144 
7.1 Overall ethical considerations 
144 
7.2 Risk-benefit assessment 
144 
8 QUALITY CONTROL AND DATA PROTECTION 
15 
8.1 Quality measures 
15 
8.2 Data recording and source data 
15 
8.3 Confidentiality and coding 
16 
8.4 Retention and destruction of study data and biological material 
16 
9 MONITORING AND REGISTRATION 
16 
10.FUNDING / PUBLICATION / DECLARATION OF INTEREST 
16 
11.REFERENCES 
17 
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GLOSSARY OF ABBREVATIONS 
AE 
ANQ 
AST 
ASR 
BASEC 
Clin O 
CRF 
CTCAE 
EQ-5D-5L 
FADP 
FIM 
eCRF 
FOPH 
GCP 
HRA 
ICF 
ICH 
LAST 
LIMOS 
MiniBESTest 
MoCA 
NHPT 
PREM 
PROM 
Short-LIMOS 
SAE 
Adverse Event 
Nationaler Verein für Qualitätsentwicklung  in  Spitälern und Kliniken 
Apraxia Screening Test 
Annual Safety Repot 
Business Administration System for Ethical Committees 
Ordinance on Clinical Trials in Human Research (in German: KIinV, in French: 
OClin, in Italian: OSRUm) 
Case Report Form 
Common Terminology Criteria for Adverse Events 
5-Level EuroQol 5D questionnaire 
Federal Act on Data Protection (in German:  DSG,  in French: LPD, in Italian: LPD) 
Functional Independence Measurement 
electronic Case Report Form 
Federal Office of Public Health 
Good Clinical Practice 
Human Research Act (in German:  HFG,  in French: LRH, in Italian: LRUm) 
International Classification of Functioning, Disability, and Health 
International Conference on Harmonisation 
Language and Aphasia Screening Test 
Lucerne International Classification of Functioning, Disability, and Health (ICF)-
Based Multidisciplinary Observation Scale 
Mini Balance Evaluation Systems Test 
Montreal Cognitive Assessment 
Nine Hole Peg Test 
Patient Reported Experience Measure 
Patient Reported Outcome Measure 
Short version of the Lucerne ICF-Based Multidisciplinary Observation Scale 
Serious Adverse Event 
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1 STUDY SYNOPSIS 
Sponsor / 
Sponsor- 
Investigator 
Luzerner Kantonsspital  Luzern, Spitalstrasse, 6000 Luzern 16 
Study Title 
Comparison of blended care outpatient neurorehabilitation with traditional outpatient 
neurorehabilitation, a crossover pilot study 
Short Title I 
Study ID 
Comparison of blended care out 
Protocol Version 
and Date 
Version 24.1 (24.12.2025) 
Study 
Registration 
Clinicaltrials.gov, Swiss National Clinical trial Portal (HumRes via BASEC) 
Study Category 
and Rationale 
Risk category A 
Background and 
Rationale 
Outpatient neurorehabilitation is crucial for managing chronic neurological conditions, but 
digital tools have yet to be fully integrated due to challenges like billing and limited evidence. 
With rising patient numbers and resource constraints, innovative solutions are needed. 
Telerehabilitation shows promise but lacks sufficient evidence. Our study aims to assess a 
blended care model combining traditional therapy with digital tools to provide a more efficient 
solution. 
We will adjust our statistical analysis for sex, to exclude any possible differences between men 
and women on their recovery rate and outcomes. 
Risk 1 Benefit 
Assessment 
The patients undergo a comprehensive medical evaluation and are checked for their 
suitability for the study to minimize risks (mainly falls). A direct beneficial effect might be 
present, when patients experience high convenience by the new set-up in the home 
environment. 
Objective 
To explore the trend to non-inferiority of a blended care model in comparison with traditional 
outpatient neurorehabilitation. 
Endpoint 
Primary: The change in total sum score between start and end of the interventions A and B 
(See chapter 3.4) on the Lucerne ICF-based Multidisciplinary Observation Scale (LIMOS) 
Secondary endpoints (at start and end of intervention A and B: 
- 
5-Level EuroQol 5D questionnaire (EQ-5D-5L) : 
- 
Short version of the Lucerne ICF-based Multidisciplinary Observation Scale (Short-
LIMOS). 
- 
ANQ-Kurzfragebogen Rehabilitation V2.0. 
The aforementioned parameters at 3 months follow-up 
Study Design 
Cross-over-design, pilot 
Inclusion-I 
Exclusion 
Criteria 
Inclusion criteria: 
•
Diagnosis of ischemic or haemorragic stroke or brain trauma. 
•
People for whom at least 6 weeks of outpatient rehabilitation is foreseen to be 
indicated. 
•
Ability for safe independent mobilisation (screening with MiniBesTest, Chedoke) 
•
Access to and ability to operate MS Teams and Apps on computer and other digital 
devices (Smartphone, Tablet) (Screening with AST, LAST and NHPT) 
•
Able to provide informed consent in German. 
•
Age: 18 - 80 years 
Exclusion criteria: 
•
Severe cardiopulmonary disease 
•
Other neurological disease than mentioned in the inclusion criteria 
•
Inability to provide informed consent in German 
Number of 
Participants with 
Rationale 
30 Patients 
Study 
Intervention 
Blended care: Participants will interchangeably receive on-site therapy and telerehabilitation 
in their home environment. Telerehabilitation will be provided by therapists via video call and 
apps. 
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Control 
Intervention 
Participants will receive outpatient neurorehabilitation in the neurology outpatient clinic of the 
Luzerner Kantonsspital,  according to current standard practice. 
Study 
procedures 
An overall study duration of ca. 5.5 to 6 months is needed, including the recruitment period 
(during last 2 weeks of inpatient rehabilitation), 1-2 weeks waiting time between discharge and 
start of outpatient rehabilitation due to organisational reasons, a 6 week intervention and a 
follow-up examination at 3 months. 
Study Duration 
and Schedule 
Planned 04/2026 of First-Participant-In 
Planned 04/2029 of Last-Participant-Out 
Investigator 
Dr. med. Noortje Maaijwee,  Luzerner Kantonsspital,  Spitalstrasse, 6003 Luzern 
E-Mail:  noortje.maaijwee@luks.ch, Tel. 041 205 19 52 
Study Center 
Luzerner Kantonsspital  Luzern, Spitalstrasse, 6000 Luzern 16 
Statistical 
Considerations: 
For the study, attention is paid to a balanced representation of the genders and the data is 
presented gender-specifically, if relevant differences are suspected. The data is recorded at 
the beginning as a baseline, after completion of the first intervention and after completion of 
the second intervention and 3 months after the end of the intervention and statistically 
evaluated. 
Data privacy 
Data protection is guaranteed by internal encryption, the separation of personal data and test 
data as well as the input in RedCap 
Ethical 
consideration 
Since the intervention has already been tested abroad, it does not pose any major risk to the 
test subjects. If the study is successful, patients will be able to choose in the future whether 
they would prefer to carry out their rehabilitation using the old or new system. 
GCP Statement 
This study will be conducted in compliance with the protocol, the current version of the 
Declaration of Helsinki, the ICH-GCP, the HRA as well as other locally relevant legal and 
regulatory requirements. 
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2 
BACKGROUND AND RATIONALE 
Over the years, the outpatient neurorehabilitation model has become a crucial component in the 
care for individuals with neurological diseases. This model, which involves an interdisciplinary 
team of physical therapists, occupational therapists, speech therapists, and neuropsychologists, 
plays a vital role in the continuum of care—from acute medical treatment to long-term 
ambulatory management of patients, many of whom experience chronic neurological deficits. 
However, as digitalization continues to transform healthcare, there are still significant barriers to 
fully integrating technology into neurorehabilitation programs. In Switzerland, for instance, 
challenges such as the inability to bill for digital services, insufficient adaptation of digital tools to 
the specific needs of neurorehabilitation, and a lack of established evidence on their efficacy, 
have hindered the widespread adoption of these innovations. At the same time, the healthcare 
sector is facing increasing challenges: more patients are surviving with neurological deficits, 
healthcare costs are rising, and there is a growing scarcity of both human and financial 
resources. This necessitates the development of innovative solutions that can ensure high-
quality care while maintaining efficiency. 
One such solution is telerehabilitation—the provision of therapeutic support remotely, allowing 
patients to receive treatment in their personal environments. Preliminary evidence suggests that 
telerehabilitation can be at least as effective as traditional, in-person neurorehabilitation.[3] 
While the available studies indicate positive outcomes, the overall quality of evidence remains 
low to moderate, and large-scale implementation of telerehabilitation in Switzerland has yet to 
occur. Additionally, we currently lack clear data on its effectiveness within the Swiss healthcare 
system. 
Therefore, our study aims to explore the efficacy of a blended care neurorehabilitation model. 
This model combines traditional, in-person neurorehabilitation with innovative digital tools such 
as synchronous video therapy, asynchronous systems using sensors to monitor patient 
progress, and standalone app-based therapies tailored to individual needs.[4] By integrating 
these new technological solutions, we eventually seek to enhance the benefits of traditional 
therapies, and in some cases, replace them, offering a more contemporary, efficient, and cost-
effective approach to neurorehabilitation. This approach could ultimately benefit all 
stakeholders—patients and their families, healthcare professionals, hospitals, insurance 
companies, and society at large—by improving care quality while addressing the challenges 
posed by the current healthcare landscape. 
We classified our Study as Category A (low risk), since the concept has been studied in other 
countries before without any reports of safety concerns. Our main safety concern would be the 
fact, that patients might perform certain exercises in a wrong way, bringing not the desired profit. 
However, we expect no persisting negative consequences, since our therapy model consists of 
blended care, where patients will be guided on-site as well within a short timeframe, where any 
false exercise implementations will be timely discovered and corrected. The risk of falling, without 
a therapist directly supporting the patient, is being minimized by careful screening of participants. 
We will adjust our statistical analysis for sex, to exclude any possible differences between men 
and women on their recovery rate and outcomes.[5] 
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3 
STUDY OBJECTIVES AND DESIGN 
3.1 Hypothesis and primary objective 
The primary objective of this study is to investigate the effectiveness of the blended care 
neurorehabilitation model in our outpatient neurorehabilitation clinic, compared with the traditional 
interdisciplinary outpatient neurorehabilitation (on-site only). We hypothesize, that the blended 
care model will show a trend towards non-inferiority in comparison with the traditional 
neurorehabilitation. 
3.2 Primary and secondary endpoints 
The change in total sum score between start and end of the interventions A and B (See chapter 
3.4) on the Lucerne ICF-based Multidisciplinary Observation Scale (LIMOS)[6] will serve as 
primary endpoint. 
The LIMOS consists of 45 items in 7 different domains, namely `interpersonal interactions and 
relationships', 'mobility', 'self-care', 'communication', `learning and applying knowledge', 'general 
tasks and demands' and `domestic life'. On every item, the therapist scores the performance of 
the participant on a Likert-scale of 1 (fully dependent) to 5 (fully independent/normal 
performance). This score has been well validated and is already in use in daily clinical practice, 
in which it is standardly filled out every two weeks as a standard assessment. 
For assessment of the efficacy of the intervention, as experienced by the patient (PROM), and 
also general patient satisfaction (PREM), the total scores on the following self-assessment 
questionnaires will be used as secondary endpoints at the start and end of interventions A and 
B: 
5-Level EuroQol 5D questionnaire (EQ-5D-5L) : First, this questionnaire assesses 5 
dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. 
Each dimension has 5 levels: no problems, slight problems, moderate problems, severe 
problems and extreme problems. The patient is asked to indicate his/her health state by 
ticking the box next to the most appropriate statement in each of the five dimensions. 
Then, a visual analogue scale is presented, on which the patient has to rate his/her 
current health status, ranging from '100, The best health you can imagine' to '0, The 
worst health you can imagine'. 
Short version of the Lucerne ICF-based Multidisciplinary Observation Scale 
(Short-LIMOS). This questionnaire consists of 18 separate items. Some items are 
combined into a mean score, so that - in the end - 10 subscores will be generated. On 
every item, the participant must choose an answer concerning how well he/she 
subjectively rates his/her performance in the activity described by the given item, on a 
Likert scale of 1 (fully dependent) to 5 (fully independent/normal performance). The 10 
subscores will be summed to one total score, ranging between 10 (worst performance 
on all subscores) and 50 (normal performance on all subscores). 
ANQ-Kurzfragebogen Rehabilitation V2.0. This questionnaire consists of 6 questions 
measuring the participants' satisfaction with the treatment. 
Also, the sustainability of the above mentioned primary and secondary endpoints will be 
measured by repeating the above assessments/questionnaires at 3 months follow-up. 
Since age, sex, location of brain damage, cognitive performance (MoCA) and severeness of 
disability  (FIM)  are potential confounders, these parameters will be recorded at baseline. 
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3.3 Study design 
This study will be a monocentric, cross-over study. After screening of eligibility and safety, 
participants will either start with the telerehabilitation blended care (intervention A) followed by 
crossover to traditional outpatient neurorehabilitation (control' intervention B) or start with 
traditional outpatient neurorehabilitation (control' intervention B) followed by crossover to 
telerehabilitation blended care (intervention A). The feasibility of telerehabilitation has already 
been documented in previous studies (e.g. Chen et al., Journal of NeuroEngineering and 
Rehabilitation, 2021; Cacciante et al., Digital Health, 2025), so this is not the focus of the present 
study. The current study aims to collect preliminary data on the non-inferiority of the treatment 
method. As funding for the study is unavailable without preliminary data, a large RCT cannot be 
implemented. As the patient group is highly heterogeneous in terms of clinical condition and 
demographic data, it is not realistic to recruit a separate control group matched for all confounders 
within a reasonable timeframe. We have therefore opted for the crossover model.[7, 8] 
3.4. Study intervention 
Intervention A, the intervention under current investigation:  
Participants will interchangeably receive on-site therapy (1 day per week) and telerehabilitation 
in their home environment (2 days per week) with an average of 180 minutes per day. 
Telerehabilitation will be provided by therapists via video call (MS Teams, available at the 
Luzerner Kantonsspital),  alternated with a practice program, implemented by the participant, 
guided by apps. The following apps will be used: 
Physiotherapy and occupational therapy: Physitrack, www.physitrack.com  
Occupational therapy and Neuropsychology:  MS-Kognition,  MS  Kognition  -  Startseite  
Occupational therapy and Neuropsychology: Brain Yoga, Brain Yoga Brain Training Game-App —
App Store  
If indicated: Speech therapy: Tactus Therapy, Tactus Therapy: Speech Therapy Apps for Adults 
with Aphasia after Stroke  
`Comparison' intervention B  
Participants will receive outpatient neurorehabilitation in the neurology outpatient clinic of the 
Luzerner Kantonsspital,  according to current standard practice, 3 days per week with an average 
of 180 minutes per day. They will receive therapies from the following disciplines: physiotherapy, 
occupational therapy and, if indicated, speech therapy and neuropsychology. 
4 
STUDY POPULATION AND STUDY PROCEDURES 
4.1 Inclusion and exclusion criteria, justification of study population 
Since the implementation of blended care rehabilitation is still in a developmental phase 
worldwide, we consider this intervention in a pilot phase. Therefore, we aim for a study 
population of 30 participants, based on the median number of participants which are usually 
included in these kind of pilot studies.[9] 
Inclusion criteria: 
•
Diagnosis of ischemic or haemorragic stroke or brain trauma. 
•
People for whom at least 6 weeks of outpatient rehabilitation is foreseen to be indicated. 
•
Ability for safe independent mobilisation (screening with MiniBesTest, Chedoke) 
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•
Access to and ability to operate MS Teams and Apps on computer and other digital 
devices (Smartphone, Tablet) (Screening with AST, LAST and NHPT) 
•
Able to provide informed consent in German. 
•
Age: 18 - 80 years 
Exclusion criteria: 
•
Severe cardiopulmonary disease 
•
Other neurological disease than mentioned in the inclusion criteria 
•
Inability to provide informed consent 
4.2 Recruitment, screening and informed consent procedure 
The recruitment will take place during in-hospital rehabilitation. When the treatment team 
decides for a patient to receive outpatient rehabilitation following discharge from in-patient 
rehabilitation, the study coordinator will screen this possible participant for eligibility and safety 
and start the informed consent procedure. 
A screening is performed using the following tests with the aim of evaluating whether the risk of 
falling is low and whether the patient can follow a home programme: 
Mini Balance Evaluation Systems Test (MiniBESTest): assessment of risk of falling (if score <20 
points); 
Chedoke: Assessment of trunk stability, arm and leg function; 
Apraxia Screening Test (AST): ability to use a computer; 
Nine Hole Peg Test (NHPT): ability to use a computer; 
Language and Aphasia Screening Test (LAST): understanding of spoken language. 
The investigators will explain to each participant the nature of the study, its purpose, the 
procedures involved, the expected duration, the potential risks and benefits and any discomfort it 
may entail. Each participant will be informed that the participation in the study is voluntary and 
that he or she may withdraw from the study at any time and that withdrawal of consent will not 
affect his or her subsequent medical assistance and treatment. 
The participant will be informed that his or her medical records may be examined by authorised 
individuals other than their treating physician. 
All participants for the study will be provided a participant information sheet and a consent form 
describing the study and providing sufficient information for participant to make an informed 
decision about their participation in the study. 
Participants will be given at least one day between information and consent. When needed, 
participants can take longer time before decision. 
The formal consent of a participant, using the approved consent form, will be obtained before the 
participant is submitted to any study procedure. 
The consent form will be signed and dated by the investigator or his designee at the same time 
as the participant sign. A copy of the signed informed consent will be given to the study participant. 
The consent form will be retained as part of the study records. 
The investigator notifies the Ethics Committee of the first study participant, in accordance with art 
62 lit. c ClinO, resp. art 38 ClinO. If the first participating person is not included in the trial within 
two years following the issuance of the authorization, the trial is considered interrupted (art. 23a 
ClinO). The clinical trial may not be commenced until an application for an extension of the time 
limit has been approved. The application for the extension is submitted to the CEC as a 
substantial amendment. 
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4.3 Study procedures 
An overall study duration of ca. 5.5 to 6 months is needed, including the recruitment period (during 
last 2 weeks of inpatient rehabilitation), 1-2 weeks waiting time between discharge and start of 
outpatient rehabilitation due to organisational reasons, a 6 week intervention and a follow-up 
examination after 3 months. Participants are allocated in a 1:1 ratio to either start with traditional 
outpatient neurorehabilitation or with blended care. Allocation is performed in REDCap®. 
See the table below for an overview of the assessments 
Time (hour, day, 
week) 
>-15d 
-14d 
Baseline 
3 Weeks 
6 Weeks 
Follow Up at 3 
Months 
Visit 
Screening 
Inclusion 
1st visit 
2nd visit 
3rd visit 
4th Visit 
Safety and 
eligibility-
Screening 
(MiniBesTest, 
Chedoke, AST, 
NHPT, LAST) 
+ 
Oral and written 
patient 
information 
+ 
Written consent 
+ 
Randomisation 
+ 
Baseline 
variables (MoCA, 
FIM) 
+ 
+ 
Primary 
Outcome 
Variable 
(LIMOS) 
+ 
+ 
+ 
Secondary 
outcome 
Variables 
(Eq-5D-5L, Short-
LIMOS, ANQ 
Kurzfragebogen) 
+ 
+ 
+ 
+ 
4.4 Withdrawal and discontinuation 
Participants are withdrawn from the study upon withdrawal of informed consent by the participant 
or if safety concerns (mainly risk of falling) exist within the treatment team, despite positive 
screening for eligibility. The participant is handled as drop-out. 
5 
STATISTICS AND METHODOLOGY 
5.1. Statistical analysis plan and sample size calculation 
The change in total sum score on the LIMOS will be compared between Intervention A and 
Intervention B with a paired t-test or Wilcoxon signed ranks test in case of skewed data. A 
correction for Age, sex, location of brain damage and baseline  FIM  and MoCA will be made, as 
these are considered confounders of the primary endpoint. The significance level will be two-
sided, with a set at 0.05 
Our hypothesis is that there will be a trend towards non-inferiority between the two groups. The 
goal is to provide preliminary data, which can be used for a power analyse for sample size 
calculation on a future randomized controlled trial. 
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See chapter 4.1 for justification of the sample size. 
Statistical analysis will be made in Jamovi, version 2.6.26110] 
In case of deviation from the original statistical plan, arguments will be described in the final trial 
report. 
5.2. Handling of missing data and drop-outs 
Only cases with complete data on the primary outcome will be analyzed. We consider other 
methods, like multiple imputation or last observation carried forward to be too vulnerable for 
outliers within a relatively small sample size. 
Drop-outs are replaced by recruitment of new participants. 
Secondary outcomes will be analyzed descriptively. 
6 
REGULATORY ASPECTS AND SAFETY 
6.1 Local regulations Declaration of Helsinki 
This study is conducted in compliance with the protocol, the current version of the Declaration of 
Helsinki, the ICH-GCP, the HRA as well as other locally relevant legal and regulatory 
requirements. 
6.2 (Serious) Adverse Events and notification of safety and protective measures 
An Adverse Event (AE) is any untoward medical occurrence in a patient or a clinical investigation 
subject which does not necessarily have a causal relationship with the trial procedure. An AE can 
therefore be any unfavourable or unintended finding, symptom, or disease temporally associated 
with a trial procedure, whether or not related to it. 
A Serious Adverse Event (SAE) (ClinO, Art. 63) is any untoward medical occurrence that 
Results in death or is life-threatening, 
Requires in-patient hospitalisation or prolongation of existing hospitalisation, 
Results in persistent or significant disability or incapacity, or 
Causes a congenital anomaly or birth defect 
Both Investigator and Sponsor-Investigator make a causality assessment of the event to the trial 
intervention, (see table below based on the terms given in  ICH  E2A guidelines). Any event 
assessed as possibly, probably or definitely related is classified as related to the trial intervention. 
Relationship 
Description 
Definitely 
Temporal relationship 
Improvement after dechallenge* 
Recurrence after rechallenge 
(or other proof of drug cause) 
Probably 
Temporal relationship 
Improvement after dechallenge 
No other cause evident 
Possibly 
Temporal relationship 
Other cause possible 
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Unlikely 
Any assessable reaction that does not fulfil the above conditions 
Not related 
Causal relationship can be ruled out 
*Improvement after dechallenge only taken into consideration, if applicable to reaction 
Both Investigator and Sponsor-Investigator make a severity assessment of the event as mild, 
moderate or severe. Mild means the complication is tolerable, moderate means it interferes with 
daily activities and severe means it renders daily activities impossible. 
Reporting of SAEs (see an°, Art. 63) 
SAEs that are possibly, probably or definitely related is classified as related to the trial intervention 
are documented and reported immediately (within a maximum of 24 hours) to the Sponsor-
Investigator of the study. 
If it cannot be excluded that the SAE occurring in Switzerland is attributable to the intervention 
under investigation, the Investigator reports it to the Ethics Committee via BASEC within 15 days. 
Falls in the domestic environment during the telerehabilitation sessions are seen as possibly, 
probably or definitely related as (S)AEs, since these might be the result of a difference between 
therapy in the clinic environment and at home. 
Exemptions from expedited reporting may be possible if the SAE is either a clear result of the 
underlying disease or well-known. Since participants have a neurological disease, the disease 
may not be stable, have an intrinsic risk of recurrence or is known for regularly occurrence of late 
consequences. Examples include a recurrent stroke in participants with stroke as primary 
diagnosis or post concussion syndrome in participants with traumatic brain injury. 
Follow up of (Serious) Adverse Events 
Patients with possibly, probably or definitely related (S)AEs will be handled as drop-out from our 
study. Since an intervention is planned for of 3 weeks, a reinclusion after stabilisation from the 
(S)AE is not aimed for. The necessary medical care will be organised by the study coordinator. 
Follow-up will be coordinated via study of the patient records or, if performed at an external 
institution, by request of the patient record after written consent of the participant. 
Relevant (S)AEs will be reported in the publication. 
Notification of safety and protective measures (see ClinO, Art 62, b) 
If immediate safety and protective measures have to be taken during the conduct of the study, 
the investigator notifies the Ethics committee of these measures, and of the circumstances 
necessitating them, within 7 days. 
6.3 (Periodic) safety reporting 
Once a year, the investigator submits to the Ethics Committee a list of the safety events including 
the severity of the events, their causality to the intervention and the safety of the study 
participants. The investigator also informs the Ethics Committee about the general progress of 
the clinical trial (ClinO, Art. 43). 
6.4 Amendments 
Substantial changes to the study setup and study organization, the protocol and relevant study 
documents are submitted to the Ethics Committee for approval before implementation. Under 
emergency circumstances, deviations from the protocol to protect the rights, safety and well-
being of participants may proceed without prior approval of the Ethics Committee. Such 
deviations shall be documented and reported to the Ethics Committee as soon as possible. 
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A list of all non-substantial amendments will be submitted once a year to the competent EC 
together with the safety report / general study progress report 
6.5 Notification and reporting upon completion, discontinuation or interruption of the 
study 
Upon regular study completion, the Ethics Committee is notified via BASEC within 30 days (ClinO, 
Art. 38). 
The Investigator may terminate the study prematurely according to certain circumstances, e.g. 
-
Ethical concerns, 
-
Insufficient participant recruitment, 
-
When the safety of the participants is doubtful or at risk (e.g. when the benefit-risk 
assessment is no longer positive), 
Alterations in accepted clinical practice that make the continuation of the study unwise, or 
-
Early evidence of harm or benefit of the experimental intervention 
Upon premature study termination or study interruption, the Ethics Committee is notified via 
BASEC within 15 days (ClinO, Art. 38). 
All health-related data are encrypted upon end of data analysis. 
6.6 Insurance 
In the event of study-related damage or injuries, the liability of the institution  Luzerner 
Kantonsspital  provides compensation. 
7 
FURTHER ASPECTS 
7.1 Overall ethical considerations 
The concept of our traditional outpatient neurological rehabilitation is well-established and is taken 
as an example by other clinics. Therefore, the effects of our telerehabilitation concept are 
expected to be generalizable to all outpatient clinics in Switzerland and even other countries with 
comparable health care offers (e.g. Western Europe). 
Telerehabilitation is still in its infancy in Switzerland. Little research has been done into its limits 
and possibilities. Therefore, we considered a pilot project suitable for our study to provide findings 
on therapy effects. 
Participants will be included only after careful consideration and evaluation if they can follow 
instructions and exercises independently to minimize risk. Since the therapy setting is in the 
patients' home environment, we expect the participants to experience more comfort in 
participating in their neurorehabilitation program. The efficacy remains to be established as part 
of the research project, but we expect this aspect to bring direct advantage to the study 
participants. 
7.2 Risk-benefit assessment 
We assume that the benefits are on a par with the traditional method and expect added value in 
terms of life balance as less time must be spent traveling to and from home. There should also 
be added value from the systematic use of media, which can facilitate rapid social and 
professional reintegration. 
However, a negative aspect could be if it becomes apparent that patients at this stage of therapy 
still have too little compliance and/or skills to be able to make optimum use of the therapies. The 
consecutive risk would be unexpected falls. Since patients are assessed by the multidiscpiplinary 
team before participation, we expect this risk to be minimized. 
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The encryption methods that the Lucerne Cantonal Hospital has generally introduced for IT 
(additional key for MS teams), the encryption of data and the use of RedCap with access via 
hospital servers minimize the risks of unauthorized access to data. 
Future patients will benefit from the data from this study as they can receive more specific therapy 
(on-site or telerehabilitation) based on the knowledge gained. We expect this concept to reduce 
healthcare costs eventually, although this remains to be established, which would offer a gain to 
society. 
8 
QUALITY CONTROL AND DATA PROTECTION 
8.1 Quality measures 
Quality assurance and quality control is guaranteed by data entry check by a second person (trial 
monitor), study personnel trained on all important study related aspects and weekly medical 
records discussion, already implemented in regular care. 
For quality assurance the sponsor, the Ethics Committee or an independent trial monitor may visit 
the research sites. Direct access to the source data and all study related files is granted on such 
occasions. All involved parties keep the participant data strictly confidential. 
8.2 Data recording and source data 
REDcap® will be used for data entry from assessments and outcome measures. 
Source data: 
Demographical variables 
Age 
Sex 
Clinical characteristics 
Primary diagnosis for inclusion 
Localisation of brain lesion 
FIM 
MoCA 
Safety and eligibility Screening assessments 
MiniBesTest 
Chedoke 
AST 
NHPT 
LAST 
Primary outcome variables 
LIMOS 
Secondary outcome variables 
EQ-5D-5L 
Short-LIMOS 
ANQ  Kurzfragebogen 
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8.3 Confidentiality and coding 
The investigator affirms and upholds the principle of the participant's right to privacy and that they 
shall comply with applicable privacy laws. Especially, anonymity of the participants shall be 
guaranteed when presenting the data at scientific meetings or publishing them in scientific 
journals. 
The investigator has appropriate knowledge and skills in the areas of data security and data 
protection or is able to ensure compliance by calling in appropriate expertise (Art. 6, ClinO). 
Individual subject medical information obtained as a result of this study is considered confidential 
and disclosure to third parties is prohibited. 
Trial and participant data will be handled with uttermost discretion and is only accessible to 
authorised personnel who require the data to fulfil their duties within the scope of the study. On 
the study specific documents, participants are only identified by a unique participant number. 
All identifying data (names, addresses, date of birth and patient number at the hospital, etc.) will 
be stored separately from the actual study data and will be only available to the Principal 
Investigator and Study Coordinator. All digital documents are password protectedsaved in a 
protected MS TEAMS Channel only accessible to persons with manually granted access by the 
Pl. 
8.4 Retention and destruction of study data and biological material 
All study data are archived for 20 years after study termination or premature termination of the 
study. 
9 
MONITORING AND REGISTRATION 
Source data and study documents are accessible upon request for monitoring. Monitoring will 
be conducted according to the separate monitoring plan. 
The study will be registered in the clinicaltrials.gov registry and Swiss National Clinical trial 
Portal (HumRes via BASEC) (after receiving ethical approval). 
10. FUNDING I PUBLICATION I DECLARATION OF INTEREST 
There are no declarations of interest. 
No separate funding is used and the project is integrated into standard care, since it is regarded 
a pilot study. Results might be used for applications for future fundings. 
Publication: We confirm that if sex and gender effects are observed, these will be published in 
the final report of the study. If an analysis is conducted but no sex and gender effects are 
observed, we will also publish this in the final report of the study. 
The sponsor enters and publishes a summary of the trial results in a public register in accordance 
with Clin0 Art. 65a within one year of completion or discontinuation of the trial. An interruption 
lasting more than two years is considered a discontinuation of the trial. 
For the purpose of publication in the public register the sponsor also ensures that a lay summary 
of the trial results is entered in BASEC within one year of completion or discontinuation of the 
trial. The entry is made at least in the national languages of Switzerland in which the study 
participants were recruited. 
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Laver KE, A.-W.Z., Crotty M, Lannin NA, George S, Sherrington C, Telerehabilitation 
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