PARTICIPANT INFORMATION SHEET
CUREC reference: R73946/RE001 Version 1.0 Date: 01/11/2020
We would like to invite you to take part in a research study. Before you decide, it is important for you to understand why the research is being done and what it will involve. 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. Please carefully consider whether you wish to take part.
1. What is the purpose of the research?
A widely used and safe drug called ‘simvastatin’, belongs to a class of drugs called ‘statins’, which are a standard medical treatment for lowering cholesterol levels to prevent heart disease. In this study we wish to find out if simvastatin changes how the brain deals with emotional information and alters levels of cortisol in people who, through feelings of isolation and/or loneliness, may have an increased likelihood of experiencing symptoms of depression.
While the main effect of statins is to lower blood cholesterol levels, statins also have important anti-inflammatory and anti-oxidant effects. Loneliness and social isolation can be associated with increased levels of inflammation and this is thought to be one physiological mechanism whereby loneliness can lead to lowered mood.
This suggests that there may be a role for statins in the prevention of some kinds of depression.
When people are depressed, or at increased risk of depression, they tend to process emotional information in a more negative way (‘look on the dark side’). This can be detected by fairly simple psychological tests carried out ‘online’. In a previous study we did find evidence that people who happened to be taking prescribed statins, even when stressed, were more likely to be ‘positive’ in the way that they deal with emotional information.
The purpose of this study is to confirm this finding by asking people to take either simvastatin or a placebo (dummy) capsule once daily for one month. In this way we should be able to find out directly if simvastatin makes people more positive in the way that they process emotional information.
In addition, we would like to carry out some measures of the natural body hormone, cortisol, in saliva. Cortisol is produced by the suprarenal glands (glands that sit above the kidneys) and levels of cortisol on waking and just afterwards are a good indicator of how ‘naturally’ stressed someone is (the higher the cortisol the greater the level of physiological stress).
Therefore, as well as measuring emotional reactions we would also like to take some measures of cortisol in saliva to see if these levels are lowered by simvastatin treatment.
2. Why have I been invited to take part?
We will be recruiting up to 100 participants in this study.
You are invited to take part in this study because you are healthy and not currently taking any regular prescribed medication, aged 30-60 years, fluent in English, capable of accessing and using a computer, and registered with a GP in the UK. You have also answered affirmatively to some questions about current feelings of isolation.
However, you may not enter the study if you:
- Currently take any regular prescribed medications (except the contraceptive pill);
- Have a history of, or current significant mental health disorder (other than a previous history of anxiety and /or depression more than six months ago.
- Have a current alcohol or substance misuse disorder;
- Have a history of, or current significant liver disease (e.g., cirrhosis);
- Have a history of, or current significant neurological condition (e.g., epilepsy);
- Have a history of stroke
- Have known high blood-sugars or pre-diabetes
- Have a known allergy or hypersensitivity to the study drug (i.e., simvastatin) or sucrose intolerance;
- Are pregnant, breast feeding, or a woman of child-bearing potential not using appropriate contraceptive measures;
- Have participated in a study that uses the same or similar computer tasks as those used in the present study (e.g., responding to positive and negative pictures of facial expressions – see below for further details);
- Have participated in a study that involves the use of a medication within the last 3 months.
3. Do I have to take part?
No. It is up to you to decide whether you want to take part in this research.
We will describe the study and go through this information sheet with you to answer any questions you may have. If you agree to participate, we ask you to sign an informed consent form. However, you would still be free to withdraw from the study at any time, without giving a reason, and without penalty, by advising the researchers of this decision. This would not affect your legal rights.
4. What will happen to me if I take part?
A researcher will contact you over the phone to go over the information sheet, explain the procedures, and go through a pre-screening with you to check that you are potentially eligible and that it is safe for you to participate. If you agree to take part in the study, you will be asked to attend three visits remotely (Screening, Baseline, and post-intervention) as well as some weekly questionnaires during the Treatment Month.
Screening Appointment (Day 0)
The screening visit will be conducted via video conference by a study medic (maximum 1 hour), who will ask you some detailed questions about your mental and physical health.
If, after they have asked you the questions, you are eligible for the study and still happy to take part, you will be randomly allocated to take either simvastatin or placebo (capsule containing sucrose): this means that you will have a 50% chance of taking simvastatin and a 50% chance of taking placebo. You will not be told which one you are taking, and we will not know either: this is in order to prevent any effects that could be caused by treatment expectations.
Information about your allocation will be stored securely during the study and ‘unblinding’ (finding out which you were taking) will only occur if it is deemed necessary for medical reasons.
You will be sent via post the study capsules with full instructions of how to take them, and a salivary cortisol test kit with instructions. You should not start taking the capsules or use the test kit at this stage.
Instead, you will be asked to contact a study researcher on the day of receiving the parcel so that a baseline visit can be arranged.
Baseline Appointment (Day 1 – within 4 weeks from the Screening Visit)
On the day of the remote baseline visit, you will be asked to use the salivary cortisol test first thing in the morning and send it back to us according to the instructions provided. Then, you will be asked to fill in some online questionnaires about yourself and your mood and to complete some computer-based tests involving simple tasks such as responding to positive and negative pictures of facial expressions, pressing buttons in response to different symbols (with the possibility to win extra money), and remembering certain numbers.
Overall, this visit will take you about 1.5 hours.
Treatment Month (Day 1 to 28-30)
During this month, you will take one capsule per day. A researcher will phone you once a week on a day previously agreed to check how you are feeling and to remind you to complete some online questionnaires again (maximum 5 minutes).
We will also send you an automated text message via FireText, which does not contain any personal data, reminding you to take one study capsule each day. You can always call us during working hours (Monday-Friday, 9am-5pm) at a research number we will provide you if you have any concerns or queries during this month; also, if there is any change in your health status or medication use, please inform a member of the study team. In case of any emergency (e.g., any sudden and significant changes in your health), please phone 111, 999, contact your GP, or attend the hospital Emergency Department as you would normally do.
Research Appointment (Day 29-31)
On day 29-31 (i.e., after 28-30 days of taking the study capsules, as previously agreed with a researcher), you will be asked again to use a second salivary cortisol test first thing in the morning and send it back to us according to the instructions provided. As before, you will be asked to fill in the same online questionnaires and computer-based tests that you completed during your baseline visit. Overall, this online research visit will take you about 1.5 hours.
In general, we would recommend you not to drink alcohol on the day and the day before you have to complete the computer-based tasks to ensure your performance is not affected by it.
5. What is simvastatin?
Simvastatin has been widely used over the last decades for preventing and treating heart and blood vessel disorders, through reducing cholesterol in the blood. Moreover, this medication has additional beneficial anti-inflammatory and anti-oxidant effects. It is usually taken orally at night-time.
6. Are there any risks in taking part?
Clinical interviews and psychological questionnaires can ask for information that might be potentially upsetting (for example, information about your mood). All clinical assessments will be performed by a qualified professional who can provide adequate information and treat any sensitive issues with care. You are under no obligation to answer the questions if they make you uncomfortable. We will also do our best to make you feel as comfortable as possible throughout the whole study.
The computerised tasks involving emotional processing have been extensively used in many previous studies with no adverse effects. It is unlikely that you will find any task distressing; you can however cease testing at any time if you do find it unpleasant.
Using the salivary cortisol test kit should not cause you any discomfort; however, it will require some planning on your part as you will need to take four consecutive samples within 45 minutes between the time you wake up and the time you get out of bed.
Potential side-effects from the drug will be monitored throughout the treatment week.
A common side-effect reported with simvastatin is mild muscle soreness or weakness; Other common (up to 1 in 10 people), but usually mild side-effects include: runny nose, nosebleed, sore throat, headache, nausea, and other problems with the digestive system (constipation, diarrhoea, flatulence, indigestion).
Very rare, but more significant adverse effects include rhabdomyolysis (a breakage of muscle fibres that can lead to severe kidney damage), diabetes (in individual with pre-existing high blood sugars), and haemorrhagic stroke (in patients with prior haemorrhagic stroke); however, the likelihood of such events is considered extremely low because of the low dosage and the short duration of treatment in this study.
Moreover, the purpose of the medical screening at the start of the study is to make sure that it is safe for you to take the study medication. If you have any negative side-effects during the course of the study, including excessive drowsiness, you should contact the research team or your GP. In general, we would recommend you do not drink alcohol and do not carry out activities requiring full alertness, such as driving, if you become aware of any impairment. If you experience any sudden and significant change in your health status please phone 111, 999, contact your GP, or attend the hospital Emergency Department as you would normally do.
7. Are there any benefits in taking part?
There will be no personal benefit to you from taking part in this research. However, by participating you are contributing to the possible future development of safer and more effective treatments to lower the rate of depression in the community
8. Will my time/travel costs be reimbursed?
Upon completion of the study, you will receive £150 for your participation in the research. Additionally, you can win up to £20 from one of the computerised tasks. If you withdraw before the end of the study, you will receive a pro-rata payment. Payment will occur via bank transfer.
9. What will happen to any samples I give?
You will be posted two salivary sample kits (one for baseline, one for the end of the study) with full instructions.
In brief, each of these kits will require you to take 4 samples in the morning 15 minutes apart, which you will put in a pre-paid, pre-addressed parcel and post to us via a post-box.
The salivary samples (four samples at baseline and four samples post-intervention) will be handled at the Neurosciences Building’s laboratory. The samples will be analysed once all participants have completed the study and then will be disposed of by the laboratory within 6 months from the end of the study.
10. What happens to the data provided?
The information you provide as part of the study is the research data. Any research data from which you can be identified (e.g., your name, contact details), is known as personal data. It does not include data where the identity has been removed (de-identified data). We will minimise our use of personal data in the study as much as possible.
Personal data (e.g., contact and bank details, consent forms) will be stored securely on University network drives, which will be firewall- and password-protected. Contact and bank details will be deleted immediately after the end of the study analysis. Consent forms will be kept for 10 years after publication of the study, and then deleted.
All other research data will be de-identified with a code and stored securely on University network drives, which will be firewall- and password-protected. Research data will be kept for a minimum of 10 years after publication or public release of the research work to comply with Wellcome Trust requirements, and then deleted.
Named researchers will have access to personal and research data. Direct access will be granted to authorised representatives from the University of Oxford for monitoring and/or audit of the study to ensure compliance with regulations.
We would like your permission to use de-identified data in future studies, and to share data with other researchers (e.g., in online databases) both inside and outside the UK and the EEA.
All personal information that could identify you will be removed or changed before information is shared with other researchers or results are made public.
11. What will happen if I don’t want to carry on with the study?
Even after you have signed the consent form, you are free to withdraw from the study at any time without giving any reason and without your legal rights being affected. If you do withdraw from the study, we will not use your data and it will be deleted.
12. Who will know that I am taking part in this research?
All information collected about you during this research will be kept strictly confidential. Any electronic data, apart from consent forms and contact and bank details will be de-identified with a code. All such data are kept on firewall- and password-protected computers.
For your own safety and with your consent, your GP will be informed of your participation in the study and will be sent a copy of the Participant Information Sheet. Any relevant medical information identified during the study procedures that requires follow-up, based on clinical judgment (e.g., a new diagnosis of depression), will be communicated to the GP after discussion with you and only if you consent to information being shared.
13. What will happen to the results of the research?
The research may be published in a scientific journal. However, no information which could be used to identify any individual participant will be published.
The research will be written up as part of a doctoral thesis. On successful submission of the thesis, it will be deposited both in print and online in the University archives, to facilitate its use in future research. The thesis will be published open access.
If you are interested in finding out about the overall results of this research, please let us know, and we will make arrangements to inform you once the study is completed.
14. Who has reviewed this study?
This study has been reviewed by, and received ethics clearance through, the University of Oxford Central University Research Ethics Committee (Reference number: R73946/RE001).
15. Who is organising and funding the research?
The study is organised by Professor Philip J Cowen, Professor Catherine J Harmer, Doctor Susannah Murphy, and Doctor Riccardo De Giorgi, sponsored by the University of Oxford, and funded by a grant from the Wellcome Trust. The researchers are not being paid specifically for including you in this study.
16. What if something goes wrong?
If a participant in research is ever considered to have suffered harm through their participation, the University has arrangements in place to provide for compensation. If you have a concern about any aspect of this study, please speak to Professor Philip Cowen (email: firstname.lastname@example.org; telephone: 01865 618311) or Doctor Riccardo De Giorgi (email: email@example.com; telephone: 01865 618238), who will do their best to answer your query. The researcher should acknowledge your concern within 10 working days and give you an indication of how they intend to deal with it.
If you remain unhappy or wish to make a formal complaint, please contact the Chair of the Medical Sciences Interdivisional Research Ethics Committee (MS IDREC) at the University of Oxford who will seek to resolve the matter as soon as possible (email: firstname.lastname@example.org; address: Research Services, University of Oxford, Wellington Square, OX1 2JD, Oxford).
17. Data Protection
The University of Oxford is the data controller with respect to your personal data and, as such, will determine how your personal data is used in the study.
The University will process your personal data for the purpose of the research outlined above. Research is a task that we perform in the public interest.
Further information about your rights with respect to your personal data is available http://www.admin.ox.ac.uk/councilsec/compliance/gdpr/individualrights/.
18. Contact Details
If you would like to discuss the research with someone beforehand (or if you have questions afterwards), please contact:
Professor Philip J Cowen
Neurosciences Building, Department of Psychiatry, Warneford Hospital, Warneford Lane, OX3 7JX, Oxford
Tel: 01865 618311
Thank you for taking the time to read the study information and for your consideration in taking part in this study.