An Investigation Into the Efficacy of Online Cognitive Behavioural Therapy for Insomnia ("Sleepio") to Improve Sleep After Stroke.
Phase: NA
Conditions: Stroke
Sponsor: University of Oxford

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Study Title:  An investigation into the efficacy of online cognitive behavioural therapy for 
insomnia (“Sleepio”) to improve sleep after stroke. 
Internal Reference Number / Short title: Improving sleep in rehabilitation after stroke 
(INSPIRES) 
NCT: 04272892 
Ethics Ref: R40803/RE001 
Protocol summary: 30/10/2020 
 
Chief/Principal 
Investigator: 
Prof Heidi Johansen-Berg, heidi.johansenberg@ndcn.ox.ac.uk, 
WIN Director, Wellcome Centre for Integrative Neuroimaging 
(WIN), University of Oxford  
Trial Manager:  
Dr Melanie Fleming, Research Fellow, Wellcome Centre for 
Integrative Neuroimaging (WIN), University of Oxford 
 
Sponsor:  
University of Oxford 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1. SYNOPSIS 
 
Long Study Title 
An Investigation into the Efficacy of Online Cognitive Behaviour Therapy for 
Insomnia (“Sleepio”) for Stroke Survivors 
Short Study Title (to be 
used on participant-facing 
documents, if applicable) 
Improving sleep in rehabilitation after stroke (INSPIRES) 
Nature of Study 
Participants 
Stroke survivors 
Intended number of 
participants 
86 
Design 
Randomised controlled 
Location 
In the participant’s home / online 
 
Objectives 
Outcome Measures 
Primary 
 
The primary objective of this study 
is to assess whether self-reported 
sleep quality in stroke survivors is 
improved following online 
Cognitive Behavioural Therapy for 
Insomnia (“Sleepio” programme).   
The primary outcome measures 
for this study will be the change 
in Sleep Condition Indicator 
score following completion of 
the programme.  
Secondary 
 
The secondary objectives are to 
assess changes in measures of 
sleep quality and self-reported 
measures of quality of life and 
anxiety following the intervention 
and at 8 week follow up. 
 
 
 
 
To assess the cost-effectiveness of 
online CBT-I in stroke survivors 
when compared to a brochure of 
sleep hygiene information. 
Changes in sleep fragmentation 
and wake after sleep onset, 
assessed with actigraphy, sleep 
onset latency assessed through 
the sleep diaries, anxiety and 
depression using the PHQ9 and 
GAD7, quality of life using the 
Stroke impact scale-8 and 
Euroqol-5 Dimensions- 5 Levels 
(EQ-5D-5L) 
 
Changes in healthcare costs 
during the 8-week follow up. 
 
 
 
 
 

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2. BACKGROUND AND RATIONALE 
Stroke is one of the leading causes of adult disability. Current physical therapies for stroke are both 
limited in their success and are time demanding, with the latter factor increasing the cost of therapy. It 
has been reported that following stroke, many people experience issues with sleep, which has been 
shown to play an important role in consolidation of learning. Our current research confirms this, 
indicating that chronic community dwelling stroke survivors experience poorer sleep quality than age 
matched healthy controls.  
 
“Sleepio” is an online Cognitive Behavioural Therapy for Insomnia (CBT-I) programme developed by 
researchers at the Sleep and Circadian Neuroscience Institute (SCNI), University of Oxford, to improve 
sleep quality. The programme takes the users through a six-week programme designed to educate the 
user on their sleep and to improve their sleep quality. The efficacy of this intervention has been 
demonstrated in people with chronic insomnia3 but has not yet been tested in people with stroke. We 
have recently conducted a mixed methods feasibility study to explore stroke survivors perceptions of 
using the programme, and this has indicated that with some additional information provided to 
participants, the programme is useable in its current form. Therefore, the present study will investigate 
the efficacy of digital CBT-I for chronic stroke survivors. 
3. STUDY DESIGN 
The study will be a single-blinded randomised controlled trial involving the completion of a six-week 
digital CBT-I programme. Following written informed consent, participants will be posted baseline 
questionnaires to complete and an actigraphy monitor to record objective sleep measures for one week. 
After this, participants will be randomised to CBT-I or control using an online randomisation software 
(rando.la) with minimisation of between group differences based on age and baseline self-reported sleep 
quality (Sleep Condition Indicator (SCI) score). The control group will be given access to an online sleep 
diary to complete daily for one week. They will also be given a brochure containing sleep hygiene 
information. 8 weeks later they will be asked to complete the online sleep diary again for one week. 
Participants allocated to Sleepio will complete daily online sleep diaries for the duration of the study and 
will receive weekly online CBT-I sessions as part of the programme.  Both groups will complete their 
programmes at home.  
Participants will be sent the questionnaires and actigraphy monitor again to be worn for another week 
immediately following completion of the programme (Sleepio) or following the 6-week sleep diary 
(control) and at 8 weeks follow up. At 8 weeks follow up, participants in the intervention group will also 
be sent a debriefing questionnaire to get feedback on the programme and the research study. 
Participants allocated to the control group will be sent a web link and activation code for the Sleepio 
programme following completion of the 8 week follow up. 
4. PARTICIPANT IDENTIFICATION AND RECRUITMENT 
4.1. Study Participants 
68 people who have had a stroke and want to improve their sleep. 
4.2. Inclusion Criteria 

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• 
Participant is willing and able to give informed consent for participation in the study. 
• 
Male or Female, aged 18+ years 
• 
> 3 months post stroke 
• 
Interest in improving sleep 
• 
Can understand verbal and written English well enough to engage with the programme and study 
procedures (with assistance from carer if needed). 
• 
Current stable health 
• 
Reliable access to internet 
• 
Currently living in the U.K 
4.3. Exclusion Criteria 
The participant may not enter the study if ANY of the following apply: 
• 
Serious physical health concerns necessitating surgery, scheduled in the next 5 months 
• 
Undergoing a psychological treatment programme for insomnia (with a health professional or 
online) 
• 
Pregnancy 
• 
Uncontrolled seizures 
• 
Untreated diagnosed obstructive sleep apnoea 
• 
Habitual night shift, evening or rotating shift-workers 
• 
Other serious clinical condition that may affect participation in the study 
5. STUDY PROCEDURES 
5.1. Recruitment 
Participants will be identified through several channels, including advertising online via social media e.g. 
Twitter and Facebook, newspaper advertisements, relevant charity websites  and by presentations at 
local stroke support groups and giving out leaflets (attached) at our public engagement events. 
 
Additionally, we will re-contact participants from previous studies who have consented to being 
contacted about future research studies by email.  
5.2. Screening and Eligibility Assessment 
We will identify participant eligibility from discussion with any interested people via email or phone 
conversations. Through these channels we will ascertain whether participants have had a stroke and 
meet the inclusion criteria. If they meet these criteria and are interested in the study, we will send them 
a copy of the participant information sheet (PIS) and the consent form. 
5.3. Informed Consent 
Written versions of the Participant Information and Informed Consent will be sent to the participants. 
The participant will be allowed as much time as they wish to consider the information, and have the 

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opportunity to question the investigators, their GP or other independent parties to decide whether they 
will participate in the study. Written Informed Consent will then be obtained by means of participant 
dated signature.  
5.4. Randomisation 
Participants will be randomised into the CBT-I or control group based using an online randomisation 
software (rando.la) with minimisation of between group differences based on baseline SCI score and age.   
All participants randomised to the control group will be offered the opportunity to undergo the Sleepio 
programme after completion of the 8-week follow up. 
5.5. Baseline Assessments 
After the signed consent form has been received by the researchers, the participant will be sent the 
GAD-7, PHQ-9, SCI, Stroke Impact Scale-8, Stroke Efficacy questionnaire and EQ-5D-5L to complete. 
Participants will also receive a questionnaire asking them to recall over the last 8 weeks all the contacts 
they have had with the healthcare service. This will be a modified version of the Client Service Receipt 
Inventory (CSRI).  
We will also ask them to wear an actigraphy monitor on their wrist for one week and to complete a sleep 
diary at the same time. We will provide them with a prepaid envelope to send the materials back.  
We will also record demographic variables including; age, sex, partner status, whether they share a bed, 
medications, employment status and date of stroke. 
 
5.6. Subsequent Assessments 
Participants randomised to the intervention group will receive access, via web link and activation code to 
the digital CBT-I programme “Sleepio”.  This programme will require the participant to keep a daily sleep 
diary and engage in weekly sessions comprising weekly CBT-I content. Participants randomised to the 
control group will be given access to an online sleep diary to complete for one week. They will also 
receive a brochure with sleep hygiene information and then will be asked to complete the online sleep 
diary again 8 weeks later. 
During the trial, participants will be asked to keep a record, in a specially designed log book, of their 
contacts with the healthcare service. 
Upon completion of the programme, participants will once again be sent questionnaires to complete 
(PHQ-9, GAD-7, SIS-8, Stroke Efficacy questionnaire and EQ-5D-5L), in addition to the wrist worn 
actigraphy monitor and the sleep diary to use for one week.  
At 8 weeks follow up, all assessments conducted as baseline will be repeated and the intervention group 
will complete a debriefing feedback questionnaire.  

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6. Feasibility and Adverse events 
6.1. Feasibility of recruitment and adherence 
We will record the number of people who express an interest in participating, the number who consent 
and the number who complete the study as an estimate of feasibility of recruitment to the study and 
completion of the CBT-I programme for this population.  
Where known, we will record any reason for declining to take part or withdrawal from the study.  
We will also send a debriefing questionnaire to participants at the end of the study to ask for their 
opinions of the study and the sleep improvement programme, and whether they had any CBT-I from 
other sources during the course of the study. 
6.2. Adverse events 
We will record any adverse effects that we are notified of, regardless of group allocation.  
7. Definition of End of Study 
The end of study is the date of the last follow-up response of the last participant.   
8. STATISTICS AND ANALYSIS 
8.1. Description of Statistical Methods 
The efficacy of Sleepio will be assessed by comparing the SCI scores of the intervention and control 
groups from baseline to immediately post-intervention, following an intention to treat analysis approach. 
Changes in the primary outcome measure from baseline to post-intervention will be assessed with 
analysis of variance (ANOVA) (or linear mixed model or non-parametric equivalents if necessary) with 
inclusion of baseline score as a covariate. 
Secondary outcomes will be assessed with ANOVA (or linear mixed model or non-parametric equivalents 
if necessary). EQ-5D-5L responses will be converted into utility values using population preferences (van 
Hout et al., 2012) and combined with survival information to calculate Quality Adjusted Life-Years 
(QALYs). All resource use will be valued using 2018/19 unit costs obtained from healthcare 
compendiums, (Curtis and Burns 2018) NHS reference costs, 
(https://improvement.nhs.uk/resources/reference-costs/) and British National Formulary 
(https://www.bnf.org/). Costs of CBT-I will be obtained from the trial.  
 An incremental analysis will be performed, assessing the differences in costs between the two 
interventions and dividing by the difference in QALYs gained in order to generate an incremental cost-
effectiveness ratio (ICER). ICERs will be estimated using an NHS perspective. The 10 000 bootstrapped 
pairs of incremental costs and incremental QALYs will be plotted on cost-effectiveness planes to display 
the uncertainty in the estimated ICER. Cost-effectiveness acceptability curves (CEACs) will be derived to 
display the probability of the CBT treatment being cost-effective, as the ceiling ratio for the maximum 
acceptable cost-effectiveness ratio varies from £0 to £85 000 per QALY gained.  

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8.2. The Number of Participants 
68 full datasets (1:1 ratio intervention to control) are intended to be collected for this study. This is 
based on a power calculation using the between groups effect size estimate (d=1.2) from a previous 
study of digital CBT-I in people with insomnia (Espie et al., 2012). This would therefore require 24 
participants in total to find an effect. However, we wish to also include people with sleep disturbance 
who do not meet the criteria for insomnia. Based on our open-label feasibility study for digital CBT-I in 
this population (Smejka et al., 2022) we anticipate that 50% of participants will not meet the criteria for 
insomnia, and based on that study we would anticipate a more modest effect size (d=0.7), which would 
require 68 participants (assuming a=0.05 and power of 80%).  Allowing for approximately 25% drop out, 
we therefore aim to recruit 86 participants in total. This should allow us to do a subgroup analysis 
including only people who meet the criteria for insomnia, as well as a full group analysis. 
8.3. Expenses and Benefits 
Postage of study materials will be covered by the research group by sending prepaid envelopes to the 
participants. Participants will receive a £15 shopping voucher per assessment time-point (baseline, post-
intervention and 8 weeks follow up – total £45) as reimbursement for their time to complete the 
questionnaires/assessments. Participants in the control group will be given free access to Sleepio after 
the 8 week follow up. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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PARTICIPANT CONSENT FORM 
Version 1 - 07/02/2020 
Ethics Reference: R40803/RE001 
Study Title: Improving sleep in rehabilitation after stroke (INSPIRES) 
 
Please initial 
each box 
1 
I confirm that I have read and understand the information sheet 
version _______ dated ________________ for the above study.  I 
have had the opportunity to consider the information carefully, 
ask questions and have had these questions answered 
satisfactorily. 
 
2 
I confirm that I am at least 18 years of age and have had a stroke. 
To the best of my knowledge, I do not meet any of the exclusion 
criteria outlined in the information sheet for this research.  If this 
changes at a later date during study participation, I agree to 
notify the researchers immediately. 
 
3 
I understand that my participation is voluntary and that I am free 
to withdraw at any time, without giving any reason, and without 
any adverse consequences or academic penalty. 
 
4 
I have been advised about the potential risks associated with 
taking part in this research and have taken these into 
consideration before consenting to participate. 
 
 
5 
 
 
I understand that data collected during the study may be looked 
at by designated individuals from the University of Oxford. I give 
permission for these individuals to access my data. 
 
6 
I understand who will have access to personal data provided, how 
the data will be stored and what will happen to the data at the 
end of the project. 
 
 
 
 
 
 
 
 

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7 
I agree for data collected in this study to be shared with other 
researchers, including those working outside of the UK and the 
EU, to be used in other research studies. I understand that any 
data shared will be fully anonymised so that I cannot be 
identified.  
 
8 
I understand that any personal information I input into the 
Sleepio programme will be available to Big Health Ltd. 
 
9 
I understand how this research will be written up and published. 
 
10 
I understand that this project has been reviewed by, and received 
ethics clearance through, the University of Oxford Central 
University Research Ethics Committee. 
 
 
11 
 
I understand how to raise a concern or make a complaint. 
 
 
12 
 
I agree to take part in the study 
 
 
Optional: I agree for my contact details to be kept in a secure database for the 
purpose of contacting me about future studies. I understand that agreeing to be 
contacted does not oblige me to participate in future studies. 
 
 
 
 
 
 
Yes 
 
No 
 
 
 
 
 
 
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