BIOmarkers in DEPression (BIODEP) Information Sheet for Healthy Volunteers You are being invited to take part in a research study. This leaflet explains why the research is being done and what taking part will involve. Please read the following information carefully and discuss it with others if you wish. You can talk to the researchers before you decide. If you decide to take part, after reading this information leaflet, please sign the consent form. If you decide not to take part it will not affect the standard of health care you receive in any way. Who is doing this study The research group is a consortium of five UK universities in Cambridge, Oxford, King s College London, Sussex and Glasgow, and four pharmaceutical companies Janssen, Lundbeck, Pfizer and GSK. The consortium is primarily funded by the Wellcome Trust. Some of the analyses of the samples will be funded by Janssen, Lundbeck and GSK. What is the purpose of the study? We would like to look at the effect that inflammation in the body may have on depression. To do this we will compare groups of individuals with depression who have responded more or less well to treatment with anti-depressants, or people with depression who have chosen not to take any treatment, with control subjects who do not have depression. We will look to see how they differ on the tests and scans in order to understand more about the causes and effects of inflammation and depression. Why have I been invited? You have been selected because you are a healthy person without depression. We will compare the results of the study tests of people with and without depression. Do I have to take part? It is up to you to decide whether to join the study. If you decide you do not wish to take part it would not affect the standard of health care you receive in any way. If you agree to take part we will ask you to sign a consent form. You are free to withdraw at any time without giving a reason. This would not affect the standard of health care you receive in any way. What will I be asked to do? If you choose to take part in this study, you will be asked to do: 1. An initial phone screen to check whether you are likely to be eligible 2. An eligibility interview where you will give your informed consent. You will then be asked questions used to assess your depression and any other mental health problems. You will also be asked about your current and past use of antidepressants.
3. Blood tests, including a sample for DNA extraction 4. Saliva collection at home 5. An MRI brain scan You will also be asked to do the following optional procedures 1. A PET scan 2. A lumbar puncture, to examine spinal fluid Phone screen A member of the research team will arrange to call you to assess whether you are likely to be eligible for the study. This should take no longer than 15 minutes. The researcher may need to check with the investigator in charge of the study if you are taking any medication or have any medical condition, but they will let you know the outcome within a few days. Eligibility visit This visit usually takes 2 to 3 hours and usually takes place in the clinic or, if you prefer, the researcher may be able to visit you in your own home. You may discuss this with the researcher when they call. First you will have an opportunity to ask any questions you may have about the study. If you are willing to participate, you will be asked to sign the consent form. You will then be asked a series of questions about how you currently feel in relation to your depression. We are looking for different groups of people so there are no right or wrong answers. Next you will be asked about your current and past treatments for depression (if any) and how they made you feel. It would be helpful if you can bring any current (or past) medications with you so that the researcher can check the prescription. Don t worry if you can t find them or can t remember. The researcher will ask for your permission to check with your GP (or other doctor) to get the details. At this point, the researcher will let you know if you appear to be eligible for the study. If you seem to be eligible, you will be given a more in-depth clinical interview about your mental health. It is possible that the discussion may make you relive some unhappy personal experiences of your own. If any of the questions or topics discussed makes you uncomfortable or upset, please let us know. If you would like to be accompanied by someone as a source of support, that is absolutely fine, but they will be asked to wait outside whilst you carry out the research project tasks. This means that for the majority of the time, they will not be with you, but they can accompany you on your breaks. You may take as many breaks as you need during the visits. The researcher will do everything they can to make sure you are as comfortable as possible. Eligibility blood test This may be performed at the same time as the eligibility visit, or it may be a few days later. You will come into the clinic in the morning and will also give a small blood sample (less than half a teaspoon). This will be tested to measure the level of inflammation in your body. This result will determine whether you are eligible to enter the study. You will then be provided with breakfast. The researcher will let you know whether you are eligible within a few days.
Clinical assessment and blood tests At the clinic visit, you will come into the clinic in the morning having not eaten or drunk anything since midnight the night before. You will give a blood sample (about 6 ½ tablespoons in total), after which you will be provided with breakfast. Some of the blood will be used for routine tests. These results will be sent to your GP. Some of the blood you give will be used for research tests and to extract your DNA. We will use this to see if there are differences between people with and without depression, and those with depression who have been helped by anti-depressants and those who have not. Your samples will be stored using your unique study number. You will not be given any information about your DNA. Your blood samples will be processed and stored in a central laboratory at the University of Glasgow and at King s College London for up to 10 years and may be used in future, ethically approved, studies. We would carry out a brief physical examination and you will be asked about your health and your family history. The visit will last for up to 2 hours. It is possible that the discussion may make you relive some unhappy personal experiences of your own. If any of the questions or topics discussed makes you uncomfortable or upset, please let us know. If you would like to be accompanied by someone as a source of support, that is absolutely fine, but they will be asked to wait outside whilst you carry out the research project tasks. This means that for the majority of the time, they will not be with you, but they can accompany you on your breaks. MRI brain scan The MRI brain scan will take around a 90 minutes to complete. This is to look at the size, shape and wiring of the brain. Though MRI scanning is generally very safe, there are certain circumstances where it must be avoided. We will go through a checklist to ask about metal objects attached to or inside your body (e.g. stents, shrapnel, plated fractures) or electronic devices (e.g. heart pacemaker). Many such items (most modern cardiac stents, for instance) are designed to be MRI safe. Being scanned requires you to lie still and relaxed on a bed in the scanner s tunnel. This tunnel is quite narrow so please let us know if you have experienced claustrophobia in small spaces. It can be noisy but earplugs are supplied and you can also have your own choice of music played over headphones if you wish. The technician performing the MRI scan would communicate with you throughout the scan to check that you stay comfortable and it can be stopped at any point.. The MRI scan will usually take place at your local centre, although you may be asked to travel to one of the other centres according to availability. This will be explained to you before you sign the consent form. PET-MR scan (optional) The PET-MR scan is an optional procedure which will give us information about the activity in the brain. You will have to travel, either to London or to Cambridge to have this scan. The PET-MR scan visit will last for approximately 2 hours, with the scan itself taking 90 minutes. We will take a small blood sample (about one tablespoon) to perform a routine test to measure inflammation. You will then have an injection of about a teaspoon of short lasting radioactive liquid. The radiation dose (2.1 millisieverts) is similar to the radiation dose we each experience from radiation in the environment during one year living in the UK. The risk of cancer associated with having this scan is extremely small (1 in 11000). For comparison, the overall risk of developing cancer in a lifetime is approximately 1 in 4. The injected radioactivity fades away naturally over a few hours and you can leave the hospital as soon as the scan is finished. If you have any concern about the dose of radioactivity, please talk to a member of the research team. We will perform a pregnancy test for female participants if there is any chance you might be pregnant. You won t be able to have a PET
scan if you are pregnant. Because the machine is a combined PET-MR machine, it will feel the same as going through the MRI machine as described above and we will go through the same checklist for metal objects. Our staff would communicate with you throughout the scan to check that you stay comfortable. You could end the scan at any point. The PET scan is an entirely optional part of the study, and you can participate in the rest of the study without having a PET scan. Lumbar puncture (optional) The lumbar puncture is also an optional procedure which will let us test for substances in the fluid (CSF) that has bathed the brain before travelling down the spine. It can tell us a lot about what is happening in the brain. The lumbar puncture will usually take place at your local centre, although you may be asked to travel to one of the other centres according to availability. This will be explained to you before you sign the consent form. If you choose to consent to this procedure, you will have an additional blood test beforehand to test how well your blood clots. A lumbar puncture involves you lying down comfortably on one side, and a trained health professional taking a sample of CSF though a small needle which is placed in the lower back, well below the spinal cord. The way the sample is collected is similar to how anaesthetists give pregnant women epidurals during labour. This sample will be used to test for possible markers of the diseases in which we are interested. This minor procedure involves you lying on one side, curled up. The skin of the lower back is thoroughly cleaned, numbed with local anaesthetic and then a very fine needle is introduced to obtain the sample. The amount of fluid collected is about one tablespoon. Afterwards, you will be asked to lie flat and rest for an hour or so and then you are free to go home. The whole time involved, including resting afterwards, is approximately three hours. A small blood sample (about a teaspoon) will also be taken after the lumbar puncture is done. It will normally take your body less than one hour to naturally replace the fluid that has been taken. It is good to drink plenty of fluids in the first few days after having a lumbar puncture (about 3 litres a day) to help your body replace the fluid and to help avoid developing a headache. You should avoid driving or operating machinery for 24 hours. If you feel fine, you can return to normal activities such as work but it is best to avoid sport, heavy lifting or strenuous activity (including heavy physical work) for at least a week. You can remove the small plaster on your back the day after the lumbar puncture. A possible side effect of a lumbar puncture is a headache, more noticeable when standing up and usually coming on within about 48 hours and resolving within three days. The probability of a headache after lumbar puncture is around 1 in 20 (or 5%). This risk is increased in people with a history of headaches. In the majority of cases (85%) this headache responds well to paracetamol and resolves with bed-rest, increased fluid intake and caffeine-containing drinks. If the symptoms persist for more than three days, strict bed-rest will be recommended. Rarely (around 1%) the headache may be more severe and associated with neck stiffness, nausea and vomiting, leading to days off work. If the headache is prolonged this may be associated with some reduction in mood. If a headache is severe or prolonged, for instance lasting over a week, you may be offered a blood patch. This involves repeating the lumbar puncture but injecting some of your own blood (taken from your arm) to seal the hole made by the original lumbar puncture. For the lumbar puncture itself, we use local anaesthetic, but there may still be discomfort in the lower back at the time, or mild tenderness or pain afterwards which settles after a short time. Occasionally there may be a little bleeding from the puncture site as sometimes happens after a routine blood sample is taken. Backache, swelling or bruising occasionally occur where the needle was inserted. This should
gradually go away on its own, but we recommend you seek medical advice if it gets worse or is still present after 5 days. Serious complications after a lumbar puncture are extremely rare. Rarer side effects include tingling and numbness in your legs, hearing loss, double vision, tinnitus and hypersensitivity to light or sound but these are so rare as to be unquantifiable. If you develop any of these symptoms, or a high temperature, seek medical advice or contact the study team (details below). The lumbar puncture is an entirely optional part of the study, and you can participate in the rest of the study without having a lumbar puncture. As with the blood samples, we are also asking permission to store your CSF sample after the end of the study within a secure and Government regulated tissue bank, so that we can measure any new gene or disease markers that are discovered in the future. This will be very valuable for our future research. What are the possible benefits of taking part? This is not a trial of any drug or other treatment and there is no direct benefit to you from taking part in this study. However if you do take part you will be making a significant contribution to medical knowledge and the challenge of depression and its treatment. Expenses If you take part in this study, we would cover all necessary travel expenses and if it would help we would arrange transport by taxi for you to come to the hospital and go home. In addition, we will reimburse you for your time and inconvenience. If you participate, you will receive 25 for the eligibility visit and blood test. If you are eligible to participate, you could receive up to a further 300 depending on which procedures you agree to do. Will my taking part in the study be kept confidential? Once you have agreed to participate in this study you will be allocated a unique study number which will be used on all your study documentation. This number will be linked to your personal information; however you will only be identified by this unique number. If you do take part in the study, all information provided to us and the results of studies would be treated confidentially. It will be stored securely in locked cabinets or on password protected computer systems, under the supervision of the Chief Investigators. We will retain the data for over 10 years. We will ask for your permission to share your data and scans in an anonymised way with collaborators, now and in the future, with other research groups, including those not funded by the Trust, including researchers in the NHS, Medical Research Council, Universities and National Institute for Health Research. You would be identified only by your unique study number. The NHS is trying to improve the quality of clinical and research standards. This is being achieved through clinical governance. As part of this process, this study may be reviewed by a clinical governance team. Such a team would need to look at our records to make sure that the research was carried out in accordance with proper procedures. What if there is a problem? Occasionally, brain scanning and other tests reveal an incidental medical problem that was not expected. Although your PET scans are for research purposes only, your MRI scan will be reviewed for major abnormalities that might require further action. If anything is seen that needs follow up, we will make sure that this information is passed on to you and/or your GP or other doctor. As this is a multi-centre study, and procedures differ slightly between sites, we will discuss the details of this with you face to face before your scan, to make sure that you understand and are happy with our
local procedures; please ask us if anything is unclear. We will also send a copy of your clinical blood test results to your GP. You will not be able to take part in the study unless you consent to us contacting your GP. Any complaint about the way you have been dealt with during the study or any possible harm you might suffer will be addressed. If you have any concerns about any aspect of this study you should speak to your study doctor who will do their best to answer your questions. In the event that something does go wrong and you are harmed by taking part in the research and this is due to someone s negligence then you may have grounds for a legal action for compensation against the Trust or the University of Cambridge. The normal National Health Service complaints mechanisms will still be available to you (if appropriate).the University has obtained insurance which provides no-fault compensation i.e. for non-negligent harm, you may be entitled to make a claim for this. If you have any concerns or comments related to your participation in this study, you could contact the Chief Investigator (details below) or the Patient Advisory and Liaison Service (PALS) at Cambridgeshire and Peterborough NHS Foundation Trust, Elizabeth House, Fulbourn Hospital, Fulbourn, Cambridge, CB21 5EF Freephone 0800 376 0775. Who is organising and funding the research? The study is primarily funded by the Wellcome Trust. Some of the analysis of the samples will be funded by Janssen, Lundbeck, Pfizer and GSK. The research team are based at the Universities of Cambridge, Oxford, King s College London, Sussex and Glasgow. The lead investigator is Professor Ed Bullmore at the Cambridgeshire and Peterborough NHS Trust and the University of Cambridge. Who has reviewed the study? All research in the NHS is looked at by an independent group of people, called a Research Ethics Committee, to protect the participants interests. This study has been reviewed and given a favourable opinion by the East of England Cambridge Central Research Ethics Committee. Further information If you would like further information please contact Professor Ed Bullmore, or any member of the research team (details below). What will happen next? The next step will be a telephone call from one of the researchers. If you are interested in helping with the study, they will arrange to meet you. This will give you a chance to ask any questions about the study and your taking part before you make a decision. If you do decide to take part, the researcher will discuss a consent form with you and ask you to sign it. It is up to you to decide whether to take part or not. You do not have to give a reason if you decide not to be involved. If you change your mind you can withdraw from the study at any time without giving a reason. You will be given a copy of this leaflet to keep. We will send you a summary of the findings at the end of the project. The research team should contact you in the next week or so. If, at any time, you need to get in touch with someone, you can contact us: Professor Ed Bullmore University of Cambridge Department of Psychiatry ***LOCAL CONTACT HERE***
Herchel Smith Building, Cambridge Biomedical Campus Cambridge, CB2 0SZ Tel: 01223 336582 Email: etb23@cam.ac.uk