Lifestyle Counselling as Secondary Prevention in Patients With Minor Stroke and Transient Ischemic Attack: A Randomized Controlled Feasibility Study
Phase: NA
Conditions: Stroke, Ischemic, Stroke Hemorrhagic, Transient Ischemic Attack
Sponsor: Nordsjaellands Hospital

 
 
 
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Lifestyle change and health behaviour in patients with minor stroke 
and transient ischemic attack: 
A randomized controlled feasibility study 
 
 
 
Jacob Mesot Liljehult, RN, MScHS, ph.d. fellow, investigator 
Department of Neurology, Nordsjællands Hospital 
 
Supervisers 
Thomas Christensen, MD, DMSc 
Department of Neurology, Nordsjællands Hospital 
Tom Møller, RN, Ph.d. 
The University Hospitals Centre for Health Science, Rigshospitalet 
Dorthe Overgaard, RN, Ph.d. 
Institute of Nursing, Copenhagen University College, Copenhagen 
Stig Mølsted, PT, Ph.d. 
Department of Cardiology, Nephrology and Endocrinology, Nordsjællands Hospital 
Date: 23-02-18 
ID: H-17040484 
NCT: 

 
 
 
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Table of Contents 
1 
Summary ............................................................................................................................. 4 
1.1 
Objective ................................................................................................................................. 4 
1.2 
Target and study population ................................................................................................... 4 
1.3 
Methods .................................................................................................................................. 4 
1.3.1 
Study design ...................................................................................................................................... 4 
1.3.2 
Exposures and outcomes of interest ................................................................................................. 4 
1.3.3 
Recruitment ...................................................................................................................................... 4 
1.3.4 
Statistical analyses ............................................................................................................................ 4 
1.4 
Expected results ...................................................................................................................... 4 
1.5 
Discussion ................................................................................................................................ 4 
2 
Background ......................................................................................................................... 5 
2.1 
Literature review ..................................................................................................................... 5 
2.2 
Justification.............................................................................................................................. 5 
2.3 
Relevance ................................................................................................................................ 6 
2.4 
Feasibility ................................................................................................................................. 6 
3 
Purpose, Objectives and Hypothesis .................................................................................. 6 
3.1 
Purpose of the study ............................................................................................................... 6 
3.2 
Objectives ................................................................................................................................ 6 
3.3 
Hypothesis ............................................................................................................................... 6 
4 
Populations ......................................................................................................................... 6 
4.1 
Study unit ................................................................................................................................ 6 
4.2 
Target population .................................................................................................................... 6 
4.3 
Study population ..................................................................................................................... 7 
5 
Study design ........................................................................................................................ 7 
6 
Recruitment ........................................................................................................................ 8 
6.1 
Sampling procedure ................................................................................................................ 8 
6.1.1 
Source of study units – Study population ......................................................................................... 8 
6.1.2 
Inclusion/exclusion criteria for sampling .......................................................................................... 9 
7 
Data management .............................................................................................................. 9 
7.1 
Variables .................................................................................................................................. 9 
7.1.1 
Outcome variables ............................................................................................................................ 9 

 
 
 
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7.1.2 
Other variables ................................................................................................................................ 10 
7.2 
Data collection ....................................................................................................................... 12 
7.3 
Database construction and handling..................................................................................... 12 
7.4 
Data control and editing ........................................................................................................ 12 
7.5 
Data processing for statistical analysis .................................................................................. 12 
8 
Statistical analysis ............................................................................................................. 12 
8.1 
Sample size calculations ........................................................................................................ 12 
8.2 
Descriptive analysis ............................................................................................................... 13 
8.3 
Statistical analysis .................................................................................................................. 13 
9 
Validity and bias ................................................................................................................ 13 
9.1 
Data sources .......................................................................................................................... 13 
9.2 
Selection bias ......................................................................................................................... 14 
9.3 
Confounding variables ........................................................................................................... 14 
9.4 
Other biases........................................................................................................................... 14 
10 
Limitations of the study ................................................................................................ 14 
11 
Ethical considerations ................................................................................................... 15 
11.1 
Project approval .................................................................................................................... 15 
11.1.1 
Confidentiality and anonymity.................................................................................................... 15 
11.2 
Authorship and publication rights ......................................................................................... 15 
12 
Project management ..................................................................................................... 16 
12.1 
Project group ......................................................................................................................... 16 
13 
Timeline and milestones ............................................................................................... 16 
13.1 
Project organization .............................................................................................................. 16 
13.2 
Budget ................................................................................................................................... 17 
14 
Deliverables – Reporting and dissemination ................................................................ 17 
15 
References ..................................................................................................................... 18 
 
 
 

 
 
 
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1 Summary 
1.1 Objective 
Stroke is a significant cause of morbidity, mortality, and loss of independence worldwide. In Denmark 
12,000 people have a stroke per year. About one fourth of patients admitted with a stroke have had 
previous strokes or TIA. The risk of recurrent stroke is highest in the first weeks and decreasing with 
time.  
Hypertension is one of the leading risk factors for vascular diseases, including stroke and TIA, and 
lowering of the blood pressure is therefore an essential part of stroke treatment. Smoking cessation, 
physical activity, and adherence to antihypertensive and antithrombotic medication is highly 
recommended in patients with minor stroke and TIA. 
The objectives of this study are 1) to test the feasibility of a lifestyle and behavioural intervention in a 
clinical setting, and 2) to test the effect of the intervention on blood pressure in patients with minor 
stroke and TIA. 
1.2 Target and study population 
The study will include patients with acute minor stroke or TIA how are discharged to their own home. 
Patients with prior disability, severe communication problems, severe psychiatric disease, or alcohol 
abuse will be excluded. 
1.3 Methods 
1.3.1 Study design 
The study will be a randomized controlled feasibility trail. Participants (n=40) will be randomly 
allocated to either an early initiated counselling intervention with frequent follow-up sessions in 12 
weeks, or usual care. 
1.3.2 Exposures and outcomes of interest 
Participation rate and adherence to the treatment program will be the primary outcome measures of 
feasibility. Systolic blood pressure will be the primary outcome measure of effect. 
1.3.3 Recruitment 
Participants will be recruited from admissions to the Department of Neurology at Nordsjællands 
Hospital, Hillerød. 
1.3.4 Statistical analyses 
Student t-test will be used as significance test for differences in blood pressure between the 
treatment groups. 
1.4 Expected results 
We expect to estimate the participation rate and variance of the blood pressure. These estimates will 
be used in planning a future randomized controlled trail. 
1.5 Discussion 
The greatest challenge we be the participation and retention of the participants throughout the 
study period. 

 
 
 
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2 Background 
Stroke is a significant cause of morbidity, mortality, and disability, both in western countries and 
globally (1). In Denmark the incidence is around 12,000 per year (2). The life expectancy of patients 
with stroke and transient ischemic attacks has increased doing the last few decades. As a consequence 
of this the risk of recurrent stroke and other cardiovascular disease has increased. Interventions to 
reduce the risk of stroke recurrence are therefore needed.  
 
Approximately one in four patients with stroke have recurrent stroke. The risk of recurrent stroke 
is greatest closest to the incident stroke. Within the first year 12-13 percent have recurrent stroke and 
after the first year the recurrence rate is 5-6 percent per year (3). Recurrent stroke is an independent 
risk factor for loss of function, institutionalization, and death (4).  
 
The most important risk factor for stroke is arterial hypertension. Not only does it increase the risk 
of stroke considerably, it is also highly prevalent in the general population. Other lifestyle factors, such 
as smoking, physical inactivity, unhealthy eating habits, and abdominal obesity also contribute to the 
risk of stroke (5).  
 
Preventive medication is an important part of the secondary and tertiary prevention in patients 
with stroke and TIA. Most of the patients get prescriptions for antithrombotic drugs or drugs to reduce 
their blood pressure or blood lipids (6). Several studies have found that a substantial part of the 
patients discontinue the drug treatment over time (7). 
2.1 Literature review 
Previous research has attempted in different ways to change health behaviour with the aim of 
preventing recurrent strokes and other cardiovascular diseases in stroke survivors.  
 
The results of previous studies have been varying and it is therefore difficult to point out any specific 
interventions or element of interventions which would be feasible to implement in clinical practice. 
Lawrence et al. (8) found in a systematic review of 20 randomized controlled trails that multimodal 
behavioural interventions had a beneficial effect on especially blood pressure. I a similar study Deijle 
et al. (9) found that lifestyle interventions had greater effect if the intervention contained elements of 
physical activity. On the contrary Lager et al. (10) found in a systematic review of 26 randomized 
controlled trails that interventions aiming at reducing the risk of cardiovascular events in stroke 
patients had no significant effect.  
 
The time of inclusion in the previous studies has varied quite a lot. In some studies the participants 
were included within 1-2 weeks after the stroke and in others participants were included until almost 
two years after. It has been hypothesised in other patient groups that the time just after the diagnosis 
constitutes a certain window of opportunity; a limited period of time in which the patient is particularly 
receptive of information and behavioural changes (11). 
2.2 Justification 
In the last decades there has been an increased focus on the importance of health behaviour in the 
public and among patients in relations to prevention of vascular diseases. There is solid scientific 
evidence of the harmful effects of lifestyle factors, such as smoking, physical inactivity, and alcohol 
overuse. But we still lack knowledge about how to disseminate this evidence to the public and how to 
help and support patients in making suitable choses to prevent recurrence and progression of their 
disease. 
 
A particularly perspective in this context is the considerable increase of the stroke burden we have 
seen in low- and middle income countries, which is attributional to the changes in life expectancy, life 
style, and living conditions. Previously stroke and other vascular diseases were considered diseases of 

 
 
 
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affluence; now 75 percent of all strokes occur in low- and middle income countries. This change from 
infectious diseases being the primary burden to non-communicable diseases is in many ways positive, 
but is also a great challenge. We need to focus our research on treatments which are effective and 
inexpensive. 
2.3 Relevance 
This study will contribute with new knowledge about how patient counselling can be conducted in 
clinical practise and its effect on the patients’ risk of recurrent vascular disease after stroke or TIA. The 
intervention tested in the study will be implemented in current clinical practise and thereby have a 
direct effect in the secondary and tertiary prevention of strokes. 
2.4 Feasibility  
Each year the Department of Neurology at Nordsjællands Hospital admits approximately 650-700 
patients with a confirm stroke and 200 patients with TIA. Of the patients with stroke 60-65% have a 
Scandinavian Stroke Scale between 45-58. It is therefore expected that around 600 patients each year 
will fulfil the inclusion criteria. It is uncertain how many of the patients will meet the exclusion criteria. 
3 Purpose, Objectives and Hypothesis 
3.1 Purpose of the study 
The overall purpose of our research is to develop effective and clinically feasible interventions to 
prevent recurrent strokes in patients with minor stroke and transient ischemic attacks. 
3.2 Objectives 
The aim of this study is  
1) to evaluate the feasibility of a client-centred patient counselling intervention focused on smoking 
cessation, physical activity, and adherence to preventive medication in patients with minor stroke 
and transient ischemic attack, and  
2) to test the effect of that intervention on blood pressure and other cardiovascular risk factors in 
patients with minor stroke and transient ischemic attack.  
3.3 Hypothesis 
The hypothesis of the study is that early client-centred patient counselling with repeated follow-up 
sessions after discharge can reduce the blood pressure through smoking cessation, physical activity, 
and improved adherence to preventive medication in patients with minor stroke and transient 
ischemic attacks compared to simple encouragement to lifestyle change. 
4 Populations 
4.1 Study unit 
The study unit will be individual patients. 
4.2 Target population 
The target population is hospitalized patients with recent minor stroke or transient ischemic attack, 
who are discharged to their own home, with only minor neurological deficits and do not require 
specialized rehabilitation. 

 
 
 
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4.3 Study population 
We will include patients with acute minor stroke or TIA admitted to the Department of Neurology at 
Nordsjællands Hospital (n=40).  
Inclusion criteria  
- Male or female, age ≥ 18 years old  
- TIA (ICD-10 G45.9) or stroke (ICD-10 I61, I63, I64) with a Scandinavian Stroke Scale of 45-58. 
Diagnosis must by confirmed by a neurologist  
- Able to give a valid written consent  
 
Exclusion criteria  
- Severe barriers to communication  
- Not able to use a telephone  
- Severe disability prior to the stroke (WHO Performance Status >2; mobilised less than 50 % of the 
day)  
- Active abuse of alcohol or narcotics  
- Severe psychiatric illness (affective disease, dementia, schizophrenia, anxiety)  
5 Study design 
The study will be a parallel group randomized controlled feasibility trail. Participants will be randomly 
allocated to either usual care or a counselling intervention, with follow-up sessions post-discharge with 
3-4 weeks intervals in 12 weeks. 
Intervention  
Participants in the intervention group will receive targeted counselling in lifestyle changes focusing on 
smoking cessation, everyday physical activity, and adherence to preventive medication. The primary 
aim of the initial counselling session will be to assess the participant’s intentions and willingness to 
change behaviour, and to support the participant in establishing realistic goals. The participants will be 
encouraged to bring a relative or close friend to the initial counselling session, who can be a support 
for the participant after the discharge.  
 
Ahead of the initial counselling session we will do a detailed assessment of the participant’s lifestyle 
and physical condition; including an assessment of lung function and oxygen uptake.  
 
After the participants are discharged from the hospital we will do 3-4 follow up counselling sessions. 
The aim of these sessions will be to re-evaluate the previous goals or to re-assess the participant’s 
willingness to change if the participant continuous to be ambivalent about lifestyle changes.  
 
The participant’s level of physical activity will be monitored from the discharge to the last follow up 
after 12 weeks. The participant will be handed out an activity tracker from the hospital which will 
record all movement day and night. 
 
 

 
 
 
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Usual care  
Participants in the control group will receive the standard care, which include a review of prescribed 
medication, and both verbal and written encouragement of a healthy lifestyle. 
 
6 Recruitment 
6.1 Sampling procedure 
Potential candidates will be contacted by the investigator while they are in the hospital, usually within 
the first few days, and asked if they want to participate. Before inclusion a set of control questions are 
asked to evaluate eligibility and participation is approved by a neurologist.  
 
Potential candidates are informed that participation is voluntary and that consent to participation 
can be withdrawn at any time. Participation or non-participation will not affect any other parts of the 
treatment. 
6.1.1 Source of study units – Study population 
Participants will be recruited from the Department of Neurology at Nordsjællands Hospital. 

 
 
 
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6.1.2 Inclusion/exclusion criteria for sampling 
Patients will be eligible if they have one of the defining diagnoses, as confirmed by a clinical 
examination by a neurologist, and are adults and able to give a valid written consent. 
 
To make the study more feasible we will have to exclude patients who are not likely to complete 
the intervention.  
 
Verbal client-centred counselling is a significant part of the intervention and telephone counselling 
might be part of the follow-up. Therefore, patients will not be able to participate if they have severe 
communication barriers, such as aphasia, or are unable to use a telephone.  
Patients with an active abuse of alcohol or narcotics will not be eligible to participate as they often will 
need a more intense type of intervention.  
 
Motivation for physical activity is also a central part of the intervention and the participants must 
be able to be physically active by themselves. Therefore, we will not include patients who prior to the 
stroke were unable to walk freely or immobile due to other disabilities.  
 
Patients with severe mental illness often have reduced self-efficacy believes and their ability to 
change lifestyle behaviour can therefore be limited. For these groups of patients a more intensive type 
of intervention might be needed. This is beyond the scope of this study, but will be treated in another 
part of the research program. 
7 Data management 
7.1 Variables 
7.1.1 Outcome variables 
Measures of feasibility 
The primary outcome measure will be the rate of participation in the study; measured as:  
1) the proportion of patients eligible for the study out of all patients with stroke admitted to the 
Department of Neurology, 
2) the proportion of patients accepting to participate in the study, and 
3) the degree of adherence to the intervention (proportion of attendance in follow-up sessions) 
Aside from participation we will evaluate the participants’ satisfaction with the overall intervention 
and single parts of the intervention. 
Variable 
Measure 
Type/scale 
Source 
Admissions 
Number of patients admitted in the study period  
Continuous 
 
Eligibility 
Number of patients who would be candidates for 
participation 
Continuous 
 
Recruitment 
Number of participants recruited 
Continuous 
 
Adherence 
Number of participants completing the treatment 
Degree of participation 
Continuous 
 
Satisfaction 
Five level Likert Scale 
Ordinal 
 
 
 
 

 
 
 
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Secondary outcome 
Measure of effect 
The secondary outcome measure will be arterial blood pressure measured 12 weeks after the start of 
the intervention. The arterial blood pressure will be measured as a continuous variable in mmHg. The 
participant should be sitting still and resting for ten minutes before the measurement. To avoid 
extreme values the measurement will be repeated three times with a few minutes apart and the 
median value will be used for the statistical analysis. 
 
This outcome measure was chosen because hypertension is the most significant risk factor for 
stroke and TIA (5) and because previous studies have found that it might be possible to lower the blood 
pressure through lifestyle interventions (8). 
 
Tertiary outcomes 
Tertiary outcomes after 12 weeks will include: 
Variable 
Measure 
Type/scale 
Source 
Changes in behavior 
 
 
 
Smoking 
Daily; weekly; Rarely; Former; 
Never smoked  
Categorical 
B 
Physical activity 
Questionnaire  
Ordinal 
B 
Adherence to medication 
Questionnaire 
Continuous 
B 
Anthropometric measures  
 
 
 
Body weight 
Measured (kg) 
Continuous 
C 
Height 
Measured (cm) 
Continuous 
C 
Waist + hip circumference 
Measured (cm) 
Continuous 
C 
Patient reported outcomes 
 
 
 
Fatigue 
Questionnaire 
 
B 
Self-rated health 
Two item questionnaire  
Categorical 
B 
 
Secondary outcomes after one year will include: 
Variable 
Measure 
Type/scale 
Source 
New stroke/TIA 
Event + days till event 
Categorical/time 
A 
Cardiac admission 
Event + days till event 
Categorical/time 
A 
Death 
Event + days till event 
Categorical/time 
A 
 
 
 
 
 
7.1.2 Other variables 
Baseline data 
Before the participants are randomized following baseline data will be collected (the brackets state 
the type of data): 
 
 

 
 
 
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Variable 
Measure 
Type/scale 
Source 
Diagnosis 
ICD-10; established through 
clinical exam/CAT scan 
Categorical 
A 
Gender 
Male/Female 
Categorical 
A 
Birthdate 
 
Date 
A 
Symptom unset 
 
Date/time 
A/B 
Admission  
 
Date/time 
A 
Living arrangement 
Living alone; living with 
partner; care facility; other 
Categorical 
B 
Performance status (prior) 
WHO performance status 
Ordinal 
B 
Self-rated health 
Two item questionnaire 
Ordinal 
B 
Alcohol consumption (/week) 
Within/above recommended 
level (7/14 units/week)  
Categorical 
B 
Smoking 
Daily; weekly; Rarely; Former; 
Never smoked  
For current smokers the 
amount and type of tobacco is 
also recorded 
Categorical 
B 
Physical activity 
 
Ordinal 
B 
Comorbidities 
Charlson’s Comorbidity Index: 
Aggregated scale based on 
weighted scores of presence 
or non-presence different 
diseases 
Individual diseases or groups 
will be coded as Y/N and the 
CCI will be calculated from 
these  
Ordinal 
A/B 
Body weight 
Measured (kg) 
Continuous 
C 
Height 
Measured (cm) 
Continuous 
C 
Waist + hip circumference 
Measured (cm) 
Continuous 
C 
Stroke severity 
Scandinavian Stroke Scale; 
Sub-scores: Consciousness, 
eye palsy, arm palsy, hand 
palsy, leg palsy, orientation, 
speech (dysphasia), facial 
palsy, gait 
Ordinal 
C 
Vital signs 
Early Warning Score; 
Sub-scores: Respiration rate, 
oxygen saturation, heart rate, 
temperature, systolic/ 
diastolic blood pressure, 
consciousness 
Ordinal  
C 
Cardiac rhythm  
ECG: Normal; arterial 
fibrillation; other arrhythmia 
Categorical 
C 
Blood glucose 
S-glucose at admission; HbA1c  Continuous 
C 
Blood lipids  
Total cholesterol, LDL, VLDL, 
HDL, triglycerides 
Continuous 
C 
 
 

 
 
 
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7.2 Data collection 
All data will be collected by one of the study investigators using electronic case report forms (eCRF) on 
the RedCap platform. Only consent forms will be on paper. 
The sources of data will be either:  
A) Electronic medical records. At this point it is not technically possible to transfer data from the 
electronic medical records and the data therefore to be entered manually using the eCRF, 
B) Structured interviews with the patients (and relatives if allowed) using standardized questions, 
C) Clinical or para-clinical examinations of the patient 
7.3 Database construction and handling 
Identifiable data (Names and CPR numbers) will be kept separate from any sensitive data. It will be 
kept in a key file on another data drive on another server than any other data. 
Electronic data will be stored on a Region Hovedstaden server with automatic access logging and data 
back-up. Access to the data will be password protected using Region Hovedstaden user id (BAM ID).  
All paper forms (consent forms) will be stored in a looked cabinet in the Department of Neurology at 
Nordsjællands Hospital. 
7.4 Data control and editing 
To avoid extreme values the eCRF will have set ranges of plausible values for numerical variables and 
it will not be possible to enter values outside the ranges. 
Before data analysis the data will be checked for missing values. If values are missing we will attempt 
to reconstruct the information from medical records or by contacting the participant. 
The data will be tested for abnormal values by the primary investigator:  
Dates – The dates of symptom unset, admission, and discharge will be compared to ensure the 
differences are not unrealistically bigger than expected, and by testing if any dates are outside the 
study period. 
Categorical variables – Will be checked for missing or illegal values with frequency distributions 
Numerical variables – We be checked for extreme/illegal values with summary statistics and by 
histograms/boxplots 
7.5 Data processing for statistical analysis 
The primary outcome measure is systolic blood pressure, which is rarely normally distributed. To 
make it normally distributed before analysis it should probably be transformed using the natural 
logarithm. 
8 Statistical analysis 
8.1 Sample size calculations 
The study in the current form is a randomized feasibility study where the main objective is to 
test if the intervention and study design is feasible enough for a full size study randomized 
controlled trail. We will therefore only include 40 participants in this phase of the study. 
 

 
 
 
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A full size randomized controlled trail will no doubt require a larger sample size if we were to expect 
an effect to be found. In a meta-analysis of fairly similar interventional studies Lawrence et al. found 
that the weighted means of the systolic blood pressure were 132.5 (SD 18.3; n=682) mmHg in the 
intervention groups and 136.2 (SD 21.5; n=725) in the control groups, respectively, and with a mean 
difference of 4.21 mmHg (95%CI 2.18-6.24). 
Using the estimates from Lawrence et al. we can estimate the sample size needed with the method for 
comparing two means as reported by Kirkwood & Stern ((12)p 420) with the following assumptions: 
- 
An equal number of participants are allocated to the two groups 
- 
The blood pressure values are approximately normally distributed 
- 
An alpha of 5 percent (probability of Type I error) and a beta of 20 percent (probability of Type 
II error) 
From this it is estimated that we will need a sample-size of 596 (298 in each group), not adjusting for 
losses to follow-up. 
 
8.2 Descriptive analysis 
The recruitment, randomization, allocation, and follow-up will be described in a flow-chart stating how 
many participants were available at each step. We will report characteristics of patients, who are 
either: excluded, non-consenting, or lost to follow-up in as much detail as possible. 
 
To ensure the external validity of the study we will thoroughly report the characteristics of the 
participants, both collectively and by treatment group. Participant characteristics will be reported in a 
table with columns for both treatment groups and a p-value for the differences between treatment 
groups. The p-values will be calculated using student’s test for continuous variables and chi-squared 
test or fisher’s exact test for categorical variables.  
8.3 Statistical analysis 
Hypothesis testing for the secondary outcome (systolic blood pressure) will be done as intention-to-
treat (including all participants allocated) using a parred t-test comparing baseline systolic blood 
pressure with systolic blood pressure measured after 12 weeks. Results will be reported as mean 
difference of changes with 95 percent confidence intervals. 
 
Tertiary outcome measures will be analyzed as intention-to-treat using unpaired student t-test for 
continues variables and either chi-squared test or fisher’s exact test for categorical variables. 
Treatment allocation will be blinded to the investigator. 
 
Statistical analyses will be done in R 3.3.1/R Studio 0.99. A significance level of 5 percent will be 
considered statistically significant. 
9 Validity and bias 
9.1 Data sources 
Administrative information (e.g.  time of admission/discharge) is recorded real-time and is therefore 
reasonably reliable. Medical information (e.g. comorbidities) should be confirmed by clinical or para-
clinical tests if possible. All information obtained from the medical records will be verified with the 
participant to sort out flawed information.  
 
The validity of information obtained from participant interviews can be affected in different ways. 
There might be problems with the internal validity of the questions used, which means that the 

 
 
 
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answers that are given might not represent what we think they are. Also participants might not be 
completely honest in their answers and we do not always have ways to validate them. 
 
The biggest threat to the validity of the study will be missing data; especially due to participants 
been lost to follow-up. Participants will not always be missing at random. They might have some 
commonality, which will result in an uneven representation. 
9.2 Selection bias 
In the study we wish to estimate the feasibility and effect in patients who would receive the treatment 
in clinical practice. One of the criteria for inclusion in the study is the willingness to participate. Most 
likely some patients will decline the invitation to participate. There could therefore be a potential 
selection bias, which could result in a skewed estimation of the effect. 
9.3 Confounding variables 
In theory the random allocation of treatment should eliminate the effect of other confounders, as they 
would be equally distributed in the two groups. But given the limited sample-size we cannot be certain 
that this will be the case. One strategy to avoid this could be to stratify the randomization be a likely 
confounder (e.g. hypertension or smoking). But at this point we are not sure which confounder would 
be the best to stratify by and this will therefore be part of the feasibility evaluation. 
9.4 Other biases 
Ideally both participants and investigators should be blinded as much as possible in clinical trials to 
avoid confirmation bias. In this study it will not be possible to blind the participants to the treatment 
group, as they are part of the intervention.  
 
It would be a possibility to blind the assessor who conducts the follow-up measurements. But we 
cannot be sure that the assessor remains blinded, as the participant might reveal the allocation. 
10 Limitations of the study 
The study will have several limitations.  
Although a randomized controlled trail is optimal for testing treatment effects, this study design also 
has some disadvantages. Because we select eligible patients to be included in the study we will also 
introduce a selection bias. To make the study more feasible with a small sample size we will have to 
exclude patients who are likely not going to complete the intervention or who have needs beyond 
what we treat in out setting, e.g. patients with addictions. This will of cause reduce the generalizability 
of the study.  
 
This also means that we cannot use data from this study to estimate the prevalence of lifestyle- and 
behavioural factors in the target population. The prevalence of such factors will be important in 
estimating how big an effect of the intervention we could expect in the target population. If we wanted 
to estimate the prevalence we would need a representative sample of the population. 
 
Patients with other types of neurological diseases could potentially benefit from similar lifestyle 
and behavioural interventions. Part of the purpose of the study is to establish a treatment option for 
patients with minor stroke and transient ischemic attacks who are discharged to their own home, 
because treatment options for this patient group is limited at the moment. If we can establish a feasible 

 
 
 
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and effective treatment for this patient group the next step would be to test the feasibility and effect 
in other types of patients. 
 
To estimate the effect of a treatment we have to compare it to something else. As there is already 
an established patient pathway for patients with stroke we can only compare the new treatment to 
the ‘usual care’ to see if is superior to this. The disadvantage of this is that the usual care can vary 
between hospitals and countries. This can influence the transferability of the results from the study 
setting to other clinical settings.  
11 Ethical considerations 
The study will be conducted in accordance with the Helsinki-declaration (13); including respect for the 
participants’ autonomy and right to informed consent. The participants will be informed that the 
participation in the study as a whole and the single parts of it will be voluntary and that they have the 
right to decline participation at any time and without giving a cause for their refusal.  
 
The inconveniences of participating will be minor and we are convinced that the potential benefits 
will outweigh the drawbacks. The main inconveniences of the study will be withdrawing symptoms, 
associated with smoking cessation, and muscle soreness from increased physical activity. Generally 
this will be both minor and transient.  
 
The use of a control group as a comparison is necessary if we wish to find evidence of the 
hypothesised effect of the treatment and gain a better understanding of the variation in the outcome 
measures. It will also be necessary to test the feasibility of the randomization process prior to the 
design of a full scale randomized controlled trail. The treatment of the participants in the control group 
will at no point be inferior to the treatment of non-participants. 
11.1 Project approval 
The study has been reviewed by the Regional Scientific Ethics Comity (H-17040484). They ruled that 
this type of intervention did not require an ethics committee approval. 
 
The gathering, storage, and handling of sensitive personal data will require consent from the study 
participants and an approval from the Danish Data Protection Agency.  
11.1.1 Confidentiality and anonymity 
All sensitive and identifiable data will be kept confidential in accordance with the guidelines from the 
Danish Data Protection Agency. Doing the project period the data will be semi-anonymized (personal 
identifiers, e.g. names and CPR numbers, are kept separate from all other data). When the study is 
finished the data will be anonymized by deleting all identifiable data. 
11.2 Authorship and publication rights 
Results of the study will be published in peer-review scientific journals as early as possible. Results will 
be published regardless of them being positive, negative, or inconclusive. 
The principal investigator (JML) will make the first draft of all publications under the supervision of the 
other members of the project group. The order of authorship will be in order of contribution and has 
been agreed upon in the project group beforehand. The rights and responsibilities of the authors will 
be in accordance with the The Danish Code of Conduct for Research Integrity (14). 

 
 
 
Page 16 of 18 
12 Project management 
12.1 Project group 
The execution of the project will mainly be managed by Jacob Liljehult (RN) under supervision of 
Thomas Christensen (MD). 
 
The whole project group will participate in the design of the study and the analysis, evaluation, and 
interpretation of the study results. 
13 Timeline and milestones 
If three participants are recruited per week the desired number of participants could be included over 
a 14 week period. With the follow-up period of 12 weeks it will then take 25 weeks from the first 
participant is included to the last participant is finished.  
 
 
13.1 Project organization 
The project was initiated as part of the CIRE neuro/psyk research program in collaboration between 
Nordsjællands Hospital, Hillerød; The Metropolitan Univesity College, Copenhagen; and The University 
Hospitals Centre for Health Research UCSF, Copenhagen University Hospital (Rigshospitalet). 
The instigators of the CIRE neuro/psyk research program consist of researchers and managers from 
UCSF and Metropolitan University College, in collaboration with the UCSF steering committee 
consisting of representatives of the hospital managers in Region Hovedstand.
 
30-07-2018
06-08-2018
13-08-2018
20-08-2018
27-08-2018
03-09-2018
10-09-2018
17-09-2018
24-09-2018
01-10-2018
08-10-2018
15-10-2018
22-10-2018
29-10-2018
05-11-2018
12-11-2018
19-11-2018
26-11-2018
03-12-2018
10-12-2018
17-12-2018
24-12-2018
31-12-2018
07-01-2019
14-01-2019
21-01-2019
28-01-2019
04-02-2019

 
 
 
Page 17 of 18 
13.2 Budget 
The three organizations will all contribute with a share of 500,000 kr. intended for salaries. Other 
expenses will be covered though public or private funding. 
 
14 Deliverables – Reporting and dissemination  
Results of the study will be published in international peer-reviewed scientific journals and presented 
on national and international conferences. Results will be made public regardless of them being 
positive, negative, or inconclusive. 
 
 
  
Note 
Year 
Total 
Reserve  
Internal 
funding 
Reserve  
External 
funding 
Deficiency 
Items 
1. y 2017-18 
2. y 2018-19 
3. y 2019-20 
VIP-salary: 
  
kr. 
kr. 
kr. 
kr. 
kr. 
kr. 
kr. 
ph.d.-fellow 
  
527.420 
527.420 
527.420 1.582.260 1.000.000 
0 
582.260 
  
  
0 
0 
0 
0 
0 
0 
0 
TAP-salary: 
  
  
  
  
  
  
  
  
  
  
0 
0 
0 
0 
0 
0 
0 
Equipment: 
  
  
  
  
  
  
  
  
Equipment 
  
75.000 
0 
0 
75.000 
0 
25.000 
50.000 
Installation/service 
  
0 
0 
0 
0 
0 
0 
0 
Spending 
  
0 
0 
0 
0 
0 
0 
0 
Licences 
  
10.000 
10.000 
10.000 
30.000 
0 
0 
30.000 
  
  
0 
0 
0 
0 
0 
0 
0 
Running expenses: 
  
  
  
  
  
  
  
  
Facilities 
(NOH) 
0 
0 
0 
0 
0 
0 
0 
Provisions 
  
0 
0 
0 
0 
0 
0 
0 
Transportation 
  
0 
0 
0 
0 
0 
0 
0 
Storage 
  
0 
0 
0 
0 
0 
0 
0 
  
  
0 
0 
0 
0 
0 
0 
0 
Other: 
  
  
  
  
  
  
  
  
Conferences 
  
0 
5.000 
5.000 
10.000 
0 
0 
10.000 
Travelling 
  
0 
12.000 
12.000 
24.000 
0 
0 
24.000 
Fees (publications) 
  
15.000 
15.000 
15.000 
45.000 
0 
0 
45.000 
Training, meetings 
  
0 
0 
0 
0 
0 
0 
0 
Monitoring 
  
0 
0 
0 
0 
0 
0 
0 
Statistical assistance (NOH) 
0 
0 
0 
0 
0 
0 
0 
Proof reading 
  
0 
0 
0 
0 
0 
0 
0 
Achieving 
  
0 
0 
0 
0 
0 
0 
0 
Overhead  
  
0 
0 
0 
0 
0 
0 
0 
Tuition fee  
(NOH) 
50.000 
50.000 
50.000 
150.000 
150.000 
0 
0 
Total 
  
677.420 
619.420 
619.420 1.916.260 1.150.000 
25.000 
741.260 

 
 
 
Page 18 of 18 
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