Participant Information Sheet (PIS)
Blind Veterans and Circadian Therapeutics Sleep Health Study
Protocol Version: 2.2
Protocol Date: 20 August 2019
IRAS ID number: 248419
You are invited to take part in this research study. Please read this Participant Information Sheet in full before deciding whether or not to participate in this study. If you would like further information regarding any aspect of this project, you are encouraged to contact the Study Coordinator. Please take the time to read this carefully and discuss it with friends, family or your GP if you wish. If you have any questions, or if you would like more information, please ask us.
What is the purpose of the research?
Sleep and biological daily rhythms (circadian rhythms) are essential to maintaining the healthy balance and functioning of the mind and body. Our master internal circadian clock coordinates our body’s daily physiological and behavioural cycles to the Earth’s solar day – including daytime alertness and sleep timing, to synchronization of changes in hormone secretion, to fluctuations in mood and cognitive ability.
Sleep and circadian rhythm disruption (SCRD) is widely experienced in our communities, with the scope of the problem often underreported. Common sufferers range from teenagers, new mothers and shift workers, to individuals with depression and the severely Vision Impaired, and is an underlying feature in many of the most challenging diseases of our time, including cardiovascular disease, cancer and neuropsychiatric diseases.
In order to treat SCRD, knowledge of an individual’s circadian timing is critical to make a definitive diagnosis of underlying disruption, and secondly, to time the delivery of treatment appropriately. However, current approaches to circadian measurement are invasive and not feasible for effective monitoring in everyday settings.
In partnership with the Blind Veterans UK, we aim to develop new methods to measure biological (circadian) time to accurately detect underlying disruption of sleep and circadian patterns. To do this, the research study aims to measure a series of physiological and biological markers in Vision Impaired individuals experiencing disrupted sleep and circadian patterns.
Why have I been invited?
You have been invited to take part in the study based on your responses to Part 1: Sleep Health Survey meeting the following criteria:
Between the age of 18 and 70
- No presence of a medical disorder that might influence sleep or alertness (other than those related to blindness)
- No current diagnosis of a sleep disorder (other than those related to blindness)
- No current use of drugs known to affect melatonin production or current use of melatonin
- No travel across more than one time zone in the last 3 months
- Non-smoker
- Regular caffeine intake less than 300mg per day (e.g. one cup of coffee)
What would taking part involve?
The research study is divided into 2 main parts:
Part 1: The Sleep and Circadian Health Survey:
The aim of this survey is to identify sleep and circadian disruption experienced by Vision Impaired individuals in order to provide informed feedback to the Blind Veterans UK community about living with sleep and circadian disruption; and to assess your eligibility to take part in Part 2 of the study.
Part 2: Sleep and Circadian Monitoring Study:
The aim of Part 2 is to develop new methods to measure biological (circadian) rhythms to accurately detect underlying disruption of sleep and circadian patterns. To do this, the research study will measure a series of physiological and biological markers in Vision Impaired individuals experiencing disrupted circadian rhythms.
Part 2 of the study is divided into two separated phases:
- Part 2A involves collecting a series of urine samples to assess your biological circadian time, and;
- Part 2B involves spending two consecutive nights at the Blind Veterans UK centre tomonitorbiological, physiological and behavioural measures.
Part 2A: Circadian Assessment
Part 2A will measure the timing of your daily sleep patterns as well as your internal biological clock (known as the ‘circadian clock’). The timing of your circadian clock tells us more about your natural daily sleep and wake cycles and helps us to determine if you have a circadian rhythm sleep disorder. Symptoms of these disorders include a pattern of an incremental daily delays in your sleep and biological timing (known as Non-24-hour Sleep-Wake Disorder); or Delayed Sleep Phase Disorder, a tendency for consistently extreme late sleep and wake timing.
To determine circadian time, a circadian marker (melatonin) will be collected in a sample of your urine. For 48 hours, you will be asked to collect all urine voids in 4-hour blocks (or 8 hours during sleep). At the end of each block, a 2ml sample of the collected urine is taken, and the rest discarded, before beginning the next urine collection block. This 48-hour urine collection procedure will be repeated once per week for 4-weeks.
During this 4-week period, you will also be asked to wear a specialised watch to continuously monitor activity and light levels (similar to a FitBit). The watch will be worn at all times throughout the 4-week period, except during showers, swimming or contact sports. You will also be asked to complete a daily sleep diary, including any daytime naps, for the duration of the 4-week period
Urine collection will take place at home; however, you will have the option of remaining at the BVUK Residential Centre during the 48-hour collection periods or full 4-week period of urine collection. Your transportation to and from the facility will be covered and organised by the Blind Veterans UK.
Part 2 B: Two-day Circadian Monitoring:
Part 2B will involve high resolution monitoring of biological, physiological and behavioural measures over two consecutive days and nights at the BVUK Residential Facilities (at no cost to you).
Participation in Part 2B will follow Part 2A with a gap of up to one month to allow researchers time to determine your circadian profile and inform you of your eligibility to continue.
Following determination of your circadian time, you will begin a Pre-Study Monitoring period where you will be asked to continue to wear the activity monitor and complete daily sleep diaries for an additional 2 weeks to determine your regular sleep and wake times.
Immediately following the Pre-Study Monitoring period, you will be asked to attend the Blind Veterans UK Centre Residential Facility to be examined for two consecutive days and nights.
On the morning of admit to the Blind Veterans UK Residential Care Facility, you will be asked to refrain for consuming any caffeine, alcohol or ibuprofen. You will be admitted to the Facility about 6-hours before your scheduled bedtime, at which point you will be oriented to your suite by the study researcher and have the opportunity to eat dinner. Before the first night of sleep, electrodes will be applied to the scalp and chest and respiratory bands worn around the chest to assess you overnight sleep for any presence of undiagnosed sleep disorders.
Upon waking the next morning, you will have the opportunity to use the bathroom and will be provided with breakfast before being seated for insertion of a cannula to help us to easily draw blood at regular intervals. Commencing one-hour after you wake, a series of biological, physiological and behavioural measures will be regularly collected (hourly or 2-hourly; summarised below) until 8-hours after you wake on Day 2. This marks the end of the study and all study equipment and the IV cannula will be removed. You will have the option to sleep at the centre for one more night before being discharged from the study in the morning.
Measures to be collected include:
Blood collection: Blood will be collected via an indwelling intravenous (IV) cannula inserted into the back of the hand or forearm. Blood will be sampled hourly during waking and sleeping periods.
Saliva collection: Saliva will be collected via the drool method by gently tilting the head forward and allowing saliva to pool in the mouth before directing into a collection tube. Saliva will be sampled hourly during waking and sleeping periods – you may be woken to provide a saliva sample over the 8-hour sleep period.
Skin temperature: A measure of skin temperature will be collected via wireless temperature sensors that sits on the skin with adhesive tape. Skin temperature monitors will be positioned on the chest and wrist.
E.E.G. and E.C.G.: Electroencephalography (E.E.G.; Electrical brain activity) and electrocardiography (E.C.G.) will be collected continuously for the duration of the study to measure electrical brain and heart information. During wake periods, a task called the Karolinska Drowsiness tests (KDT) will be used to sample E.E.G. The KDT involves sitting quietly for 3 minutes with eyes open and head directed forward, followed by 2 minutes with eyes closed and head directed forward.
Performance, mood and alertness: Your performance will be assessed via auditory reaction time tasks, and measures of subjective mood and sleepiness will be measured via visual analogue scales.
Activity and Light: Light and activity will continue to be monitored via the actiwatch monitor worn for the duration of the study period.
Light perception test and melanopsin function test: This test aims to determine the degree of light perception and residual functioning of your eyes.
All devices have FDA 510K and medical CE clearance for use as medical devices in humans.
Throughout your waking periods, room lights in your suite will remained dimmed (Day 1 and 2), and darkness (<0 lux) during sleep periods, to reduce impact of light on circadian markers. You will be free to move around the suite in between testing periods and all meals (breakfast, lunch, dinner and snacks) will be taken in your private suite.
What to expect during the consent process
If you would like to take part in Part 2 of the study, you will be invited to attend a Participant Information and Consent (P.I.&C.) meeting with researchers a Blind Veterans UK Centre.
The P.I.&C. meeting will involve the following (approximately 1 hour):
- A detailed review of the research and informed consent: A one-on-one meeting between youand the researcher where you will review the full study requirements together and complete the
informed consent form if you choose to take part in the research. - Eye examination by an ophthalmologist to document your vision health status: This examination
will be administered by registered Ophthalmologist. The examination will involve dilating the pupilof the eye, and then looking into a small machine that shines a dim light at one eye for 10-20
seconds. The reaction of your pupils to light is measured by the machine. There are no side
effects anticipated from this measurement. The dilating drops can sometimes make your vision
feel blurry for up to 4 hours, and we would advise you not to drive for this time. We can provide a
record of your eye exam to your health provider if you wish.
- A blood test to assess your general health. The blood test will be administered by a BlindVeteransUK nurse and we can provide a record to your health provider if you wish.
During this meeting, you will also be provided with a Urine Collection Kit – including urine
materials, talking scale, sampling equipment, and instructions – as well as an Actiwatch and sleep
diary.
What are the possible benefits of taking part?
Participation in the research will contribute to the development of effective markers to predict
circadian time. This will provide new methods to more simply determine a diagnosis of underlying circadian disruption, and secondly, to time the delivery of treatment appropriately.
What are the possible disadvantages and risks of taking part?
We have identified some disadvantages and risks involved in taking part in the research. Please take the time to read this carefully and discuss it with friends, family or your GP if you wish. If there is anything that you do not understand, or if you would like more information, please ask us.
During Part 2A, collection of urine voids for 48 hours over 4 weeks may cause inconvenience to you and a temporary change to lifestyle. The following strategies will be in place to minimise burden:
- All instructions, sample collection equipment and record keeping will be discussed in
detail with you and adapted to your individual requirements where possible to increase the
ease with procedures.
- You may request to stay at the Blind Veterans Residential Facility for the duration of urine
collection. Nursing staff will be on hand if you require assistance with any aspects of sample
collection, such as the scheduled timing of samples, handling of equipment and record keeping.You
will be provided with contact details of relevant personnel to call with any questions or
concerns about the procedures.
During Part 2B: Two-Day Monitoring study, the possible risks, side effects and discomforts beyond the normal experience of everyday life, may include the following:
Indwelling intravenous (IV) cannula:
- There may be some discomfort or bruising on initial insertion of the cannula into a vein but
wearing the cannula should not be painful. This complication is not serious and is likely to happen.
- Occasionally, there is a black and blue mark (bruising) at the site of the IV insertion, which may
last a couple of weeks. Rarely, a small scar may remain permanently at the venepuncture site.
This complication is not serious, and permanent scarring happens only rarely.
- The amount of blood drawn should not significantly alter blood volume. All members who
participate must have normal haemoglobin, haematocrit and red blood cell levels
(as measured by the blood test at P.I.&C meeting). The total volume of blood drawn over the
course of the study will be no more than 370 ml over 37 hours – less than the standard NHS blood
donation of 470 ml over 5 – 10 minutes.
- There is a rare possibility of developing a small blood clot, inflammation, or local
infection around the vein where the cannula is inserted, or in rare cases, a generalised infection
spread through the bloodstream as a result of the IV cannula. This complication is serious but
happens only rarely.
- Occasionally, mild discomfort may occur from the tube in the vein. If this happens, we
will either reposition or remove it entirely, asking the your permission before any
subsequent reinsertion.This complication is not serious and happens only rarely.
There is the possibility of faint during or after the IV insertion procedure. This complication
is not serious and happens only rarely.
- There may be a minor rash or reaction to the sterile tape (contact dermatitis) used to
hold the cannula in position. This complication is not serious and is not likely to happen.
Other:
- The tape and special gel used to attach the E.E.G. electrodes may cause some minor
discomfortor skin irritation, and the gel used to hold electrodes to the scalp may leave a flaky residue in the hair for several days. The adhesive E.C.G. pads may cause some skin irritation.These complications are not serious but are likely to happen
- All data collection equipment is electrically isolated and meets medical facility
electrical safetystandards, and is checked annually by engineering staff
What will happen if I don’t want to carry on with the study?
Participation in this study is entirely voluntary and you do not have to consent to participate. If you choose to participate, you may withdraw from further participation at any stage during the research. You are under no obligation to take part in the research or to continue the research once involved.
How will my information be kept confidential?
The study will comply with the Data Protection Act, which requires personal data to be anonymised as soon as it is practical to do so. The Chief Investigator and co-investigators will have access to your personal data. Personal data including contact information will be stored in a secure filing cabinet at the Circadian Therapeutics offices. Any documentation with identifiable (personal) data will be stored securely and separate from the research data. With your consent, we will keep your personal information on a secure database in order for you to be contacted for ethically approved future studies. You will only be identified by a unique study specific Participant Identification number in any database. Your name and any other identifying detail will not be included in any research data electronic file.
If you have also consented to take part in the Study titled ‘Melatonin Treatment for Sleep Disturbance in Ocular Disorders: The Sandman Trial’ (REC#: 17/LO/1226), your information will be shared with the Oxford University Hospitals (OUH) research team. Any documentation with identifiable (personal) data would be stored securely and separate from the research data. Further details on how your information would be used can be found in the ‘Sandman Trial’ Patient Information Sheet. Participation in the ‘Sandman Trial’ study is entirely optional and does not affect your participation in the Circadian Therapeutics-Blind Veterans UK Sleep Health Study.
What will happen to the biological samples I give?
All stored samples will be anonymized (labelled with an identifying number and not using any personal information) and kept in freezers at the Blind Veterans Centre or at the responsible laboratory for processing. The laboratory processing the samples will have no access to any personal data. Even if you give your consent to your biological samples being stored, you can withdraw this at any time without giving a reason for doing so. After completion of this study, your biological samples may be kept up to a period of 7 years before being destroyed.
Who is organising and funding this study?
The research is organised by researchers from Circadian Therapeutics in collaboration with Blind Veterans UK. The research is jointly funded by Blind Veterans UK and Circadian Therapeutics.
How have patients and the public been involved in this study?
A number of aspects of the research process have actively involved Blind Veterans UK members and staff. Members of the Blind Veterans UK, Rehabilitation Officers for people with a Vision Impairment (ROVI), Residential Care Managers, and the Head of Research and Innovation at Blind Veterans UK have been involved in several aspects of the study development and will continue to be involved throughout the study. Some aspects of involvement include, pilot testing the devices and tests, review the procedures and instructions involved in the study, identifying the most appropriate methods to contact Blind Veterans UK members, and encouraging the use of the Blind Veterans Centres for the research studies.
Informing your Blind Veterans UK healthcare providers
Outcomes from the Survey and your Ophthalmological eye exam can be shared with your Blind Veterans UK health-care provider to keep a record of your responses. Any incidental findings from the study will be reported to your GP for follow up. If you would like your information shared with Blind Veterans UK, you will have the opportunity to provide your Blind Veterans UK ID to link your responses with your records. You may request that your information is not to be linked with your Blind Veterans UK ID and not shared with Blind Veterans UK health-care providers.
Who has reviewed this study?
All research studies are checked by an independent ethics committee to ensure the research is conducted safely and to the best standards. This research has been reviewed by and received favourable opinion through the Research Ethics Committee of the NHS Health Research Authority.
What will happen to the results of this study?
We plan to publish the results of this study in a scientific and peer reviewed journal. We may also present the results at a scientific conference. We would be happy to discuss the results of the study with you and to send you a copy of the published results. It is important to note that it will not be possible to identify you in any report or publication.
What if something goes wrong?
If you have a concern about any aspect of this project, please speak to the Study Coordinator, Suzanne Ftouni, who will do their best to answer your query. If you remain unhappy or wish to make a formal complaint, please contact Dr Renata Gomes (Blind Veterans UK Head of Research and Innovation) on 0207 616 8371 or email Research@blindveterans.org.uk.
What if I have further questions?
If you have any further questions, please contact the Primary Research Coordinator, Dr Suzanne Ftouni, at sleepstudy@circadiantherapeutics.com or on 01865 546582, who will happily answer any further questions you may have.