Nuffield Department of Primary Care Health Sciences Radcliffe Primary Care Building, Radcliffe Observatory Quarter Woodstock Road, Oxford OX2 6GG Dr Megan Kirk Chang and Dr. Min Gao ( Principal Investigators) Email: DIMEStudy@phc.ox.ac.uk Study Phone Number : 01865 289288 PARTICIPANT INFORMATION SHEET D ietary I nterventions for ME ntal Health in People with T reatment - Resistant Depression: A Randomised Controlled Study (DIME) Central University Research Ethics Committee Approval Re ference: R87397/RE001 Version 1.0 Date: 21 / 09 /2023 We would like to invite you to take part in our research study, the DIME project, conducted by researchers at the Universit ies of Oxford and Sheffield . You do not have to decide today whether or not you will participate. Before you decide, it is important for you to understand why the research is being done and what it will involve for you if you wish to take part . Please take as much time as you need to read the following information carefully and discuss it with friends, family or your GP if you wish. If there is anything that is unclear, or if you would like more informati on, please ask us to explain any words or points that you do not understand fully. Overview of the DIME Study For people diagnosed with depression, antidepressant medications and psychological therapy are the main treatments offered, but not everyone wants or responds to these treatments. This study is to see whether diet can improve depression. We are looking for people with depression, who are still depressed even while on an antidepressant tablet and who have previously tried another antidepressant. Everyone will get support to change their diet. A dietitian will phone you once a week for six weeks to support you to manage your diet. We will give people advice on one of two types of diet programmes . The study aims to find out which type of diet programme works best. The fair way to test this is to decide by chance which type of diet we ask you to follow, meaning you will not have a choice about the diet we ask you to follow. We will ask you to complete questionnaires to see how the diet is affecting th e way you think and feel over 12 weeks. If you are interested in learning more about the study, please continue reading the rest of this document. 1. What is the purpose of the DIME study? Researchers at the Universit ies of Oxford and Sheffield would like to test whether following 6 - weeks of a recommended nutritional diet program with weekly dietitian support can improve depression in people who have not responded to antidepressant medication. 2. Why have I been invited to take part? You have responded to an advert on the internet. Our study is suitable for people aged 18 - 65 years old , who have a current diagnosis of depression and are on an antidepressant and still feel depressed and have previously tried another antidepressant. You need to be willing to change your diet with the support of a dietitian . You will need to be willing to complete online questionnaires that require you to have regular access to a tablet, laptop, or computer. 3. What should I consider? To be able to take part in this study, we need to confirm that you do not have any medical conditions that might make the diet programmes unsuitable for you. The programme is NOT suitable if you are/have : • Currently receiving or have received inpatient psychiatric treatment or electroconvulsive therapy within the past year, or are scheduled to receive such treatment during the study • Currently using St John’s wort or other remedies for depression not prescribed by a doctor. • Currently have strong thoughts about ending your life or tried to end your life in the past two months • Ever had an eating disorder, bipolar disorder, schizophrenia, or psychosis • Have substance use or alcohol dependence • Have epilepsy • Have gallstones, renal tubular acidosis, kidney stones, small bowel malabsorption, or a history of pancreatitis • Eat a vegan or vegetarian diet • Have food allergies ( experiencing food hypersensitivity that leads to anaphylaxis or other severe symptoms, which may require hospitalisation or are life - threatening ) or other special diets that make dietary interventions difficult or impossible • C urrently treated with insulin, glibenclamide , canagliflozin, empagliflozin, dapagliflozin, ertugliflozin , liraglutide, semaglutide, dulagl u tide, l ixisenatide , exenatide • Currently pregnant, planning pregnancy in the next 3 months , or breastfeeding • Have a body mass index (BMI) of less than 18.5 kg/m 2 • Drink a lot of alcohol or use ilicit drugs regularly • Have gallstones, renal tubular acidosis, kidney stones, small bowel malabsorption or a history of pancreatitis • Taking part in other research studies • Have surgery planned in the next 3 months • Living in the same household as another person taking part in the trial or read the trial protocol or trial registration. Most people with other illnesses are able to take part, but if we judge that the illness makes you too poorly or is likely to need extra treatment that interferes with your participation in this study, we will ask you not to take part. To take part in the study you need to • Have a desktop, laptop, or tablet computer • Have both a fridge and a freezer at home • Be w illing to provide saliva, urine (pee), and stool (poo) samples 4. Do I have to take part? No, you do not have to take part in this study. It is up to you to decide whether to take part. Even after you have signed the consent form, you are free to withdraw from the study at any time without giving any reason . If you choose to withdraw, any personal data or information you have contributed to this research study will be used unless you ask us to destroy it. A ny data that has already been collected will be summari s ed as aggregated group data only, with no identifying information being linked to you. 5. What will happen to me if I take part? First , we will check the study is appropriate for you . We will ask you to fill in a short online questionnaire about your health , thoughts , and feelings and some practical issues If you seem suitable at this stage, we will ask you to fill in an online consent form to show that you understand what we are asking of you and ask you for your name and contact details. We will call you to ask you questions that are best ask ed in conversation. If you still want to take part and we think the study is right for you, we will ask you to complete your first assessment, which can be done on the same day as the phone call or later. The study lasts 12 - weeks and for the first 6 weeks, a dietitian will ring you every week to support you to change your diet in a way that could help your depression. We are testing two diets to see which one helps the most. We will decide at random, like tossing a coin, w hich diet you follow The dietitian will explain t he diet to you and give you 20 - 30 minutes advice every week to help you understand and follow the diet. We will give you some pre - packaged food or vouchers to help you follow the diet. If you get food, you will need to have someone in the house to receive the food parcels and store the food, some of it will need to go in the fridge. You may need to test your urine with a dipstick, which will help you know whether you are sticking to the diet. We may send you t ext messages or emails giving advice on what foods to eat and advice on how to help you stick to your diet during the week. The diet s are not aiming to help you lose weight and we do not expect you will lose weight during the study. If the diet seems to have helped, we will suggest you continue to follow it for as long as you like but we will stop supporting you at 6 weeks We need to see whether these diets affect your mental health. To do so, we will ask you to complete questionnaires about how you think and feel at the beginning and every 2 weeks during the diet until 6 weeks. We will ask you to complete the same questionnaires again at 12 weeks , where we will also ask you whether you are still following the diet We will also ask you to complete a task to assess how you learn, which usually changes in depression. We will ask you to do this task at the beginning of the study and again at 6 weeks. Altogether, the questionnaires a t the beginning will take about 30 minutes The questionnaires and assessment at 6 and 12 weeks will take about 30 minutes to complete and the questionnaires at 2 and 4 weeks will take 5 minutes. We aim to understand how these diets might affect you r body . Depression affects your hormones , and we will ask you to measure the hormone cortisol. To do so, we will ask you to collect saliva (spit) . This means you will put a dental roll in your mouth for about 2 minutes four times over the first hour of your day. In between you can do your normal activites. You will do this at the beginning of the study and again at 6 weeks. Diets affect the microbiome, which is the community of bacteria (bugs) that grow in our bowels. We will therefore ask you to give us a sample of your stool (poo) at the study start and at 6 weeks to see how your microbiome changes It is quick, safe , and hygienic to collect the stool sample . You will collect it in a similar way as used in the NHS for bowel cancer screening. Th is will take you about 5 minutes. We may ask you to test a sample of your urine (pee) twice a week for six weeks. To so, we will ask you to urinate (pee) in a plastic cup first thing in the morning and dip a testing stick into it and record the colour of the test on a chart. You can then tip the cup contents into the toilet This will take you about 2 minutes. A t 12 weeks, we may also ask if you’d like to have a 1:1 discussion over the phone for about 3 0 minutes to talk about your experience in more detail. One of our researchers will call you for this and will ask to audio - record it so we can best make use of the information you provide. The recording will be kept entirely confidential. All identifying information will be removed and not linked to you directly. This is to help us understand what parts of the diet programme were helpful and how it could be improved in the future. 6. Are there any possible risks in taking part? There are no known serious risks from participating in the diet programmes offered in this study. However, some people can have symptoms when they change their diet including head and body aches , fatigue, and constipation or diarrhoea, but these symptoms usually settle over a few days as your body gets used to new food. Your dietitian will be there to help you manage these problems if they occur. The questionnaires we will use to ask you about your mood, emotions, and thoughts as you’re following the diet programme have been used in many other studies and we do not expect these to have any risks. Reflecting on how you are feeling may cause some upset but these are usually passing feelings. It is painless and easy to collect saliva , urine , and stool (poo) samples , but some people find collecting this slightly discomforting. 7. Are there any benefits in taking part? You may benefit from taking part and changing your diet, but we are conducting this study to find out if this is true. By taking part in this research study, you will be helping us work out how to best help more people with depression and whether diet is a useful treatment for depression and so benefiting other people. 8. Will my general practitioner/family doctor (GP) be informed of my participation? Yes, we will inform your GP that you are taking part in our study by letter. Taking part in the study will not affect the clinical care you receive from your GP for depression or any other unrelated conditions. If you tell us you are planning to end your own life, we will get in touch with your GP to let them know so that they can give you the support you need. If the risk is very high, we will phone 999. 9. Are there any costs to take part in this study? No, there are no known additional costs required to participate in our study. 10. Will I be reimbursed for taking part in this study? Yes, as part of the diet programme, you may receive specific food products, a grocery voucher, or diet supplement s to help you stick to your 6 - week diet programme at no cost to you. To thank you for your time and contribution to science , you will receive up to £80 in financial compensation via vouchers for the time you spend in our study: • £10 for completion of week 2 assessments • £10 for completion of week 4 assessments • £30 for completion of week 6 assessments (end of diet programme) • £30 for completion of week 12 assessments (follow - up) • £10 for completion of the qualitative interview (after 12 weeks ) 11. What will happen to any samples I give? We may ask you to test your urine. To do this, you will urinate (pee) in a plastic cup and put a plastic testing strip in. You will then tip your urine into the toilet. When you give your saliva and stool (poo) samples, you are donating your samples to use to be analysed. All samples will be handled, analysed, and disposed of according to standard University of Oxford procedures. Your saliva and stool (poo) samples will be analysed at approved laboratories to measure your morning cortisol levels and the bacteria composition in your gut. Your sample results may be shared with your GP in the very unlikely event that they suggest something of concern. We will dispose of the s amples once they have been analysed. We will ask you to label your samples only with your study number 12. What information will be collected and why is the collection of this information relevant for achieving the research objectives? Consent: We will ask everyone who wants to take part to fill in an online questionnaire, but this does not ask for your name. We will keep the information you give as a record of how many people wanted to take part and the reasons that they could not do so. We will ask anyone who seems suitable for the study to agree to take part by completing an informed consent form. This is considered identifiable data because it includes your name and contact details W e will securely store your consent form and contac t details on a secure drive separately from the rest of the data we collect about you. Contact Details: Because this research study will involve mailing saliva and stool (poo) test kits, and may include providing food products, vouchers, supplements, or financial compensation by vouchers , you will be asked to provide us with your email address, phone numbers, and mailing address. We will need to share your name and address with any food companies that send you food, but they will have no other information about you. Research Data: All information obtained during this study, including your personal information, questionnaire /task responses, and saliva and stool sample results will be kept strictly confidential and will not be shared with anyone outside the study. Electronic data for analysis will be stored on University servers that only the p rincipal i nvestigator , project coordinators, and research team have access to. Data will be stored for 7 years after you complete the study after which it will be permanently destr oyed. Discussion Data: After you have finished the questionnaires , you may be invited to take part in a 30 minute discussion with one of the members of our research team. These discussions will be audio - recorded if you agree to that We will store the recording securely linked only with your study number until we have analysed it and t h en we will destroy it. Important note : To protect your data confidentiality, you will be assigned a unique 3 - digit alphanumeric ID when you enrol in the study. This ID will be the only variable used to connect your data across assessments and to keep track of individual cases in our analysis. Your personal information will be stored in a separate file from all other documents in a secure drive with limited access on a strictly need - to - know basis, using password protection . We will retain your contact details to communicate inform ation to you , ask you to complete assessments, and give you financial compensation for your time If you have elected to be contacted about future studies, we will put your contact details and that you took part in this study on depression in a separate file on our secure server so we can contact you. 13. What will happen if I decide to not continue with the study? Your participation in this study is entirely voluntary and up to you. If you decide you do not want to take part in this study at any point, even after you’ve started, that is fine. You can withdraw from this study at any time without giving us a reason. W e will give you the opportunity to tell us the reason for your withdrawal if you would like to. If you decide to withdraw, you may withdraw without penalty, financial or otherwise, and you will still receive your financial compensation for your pro - rat a co mpletion of the study assessments . If we do not hear from you, all data that has been collected will be used in the study analysis. Your data will be summari s ed as group - data only with no personal identifying information. 14. Will the research be published? Could I be identified from any publications or other research outputs? The findings from the research may be written up and reported in peer - reviewed academic journals and presented at regional, national, and international conference s to infor m future clinical, policy, and research strategies aimed at treating treatment - resistant depression. Only anonymised, aggregate - level group data, without any identifiers will be used in these scholarly documents and presentations. You will not be identified in any report or publication from this study. In the 1:1 discussions, we will seek your permission to use direct quotations, and remove any personally identifying information, in any research outputs. Further anonymisation procedures will be conducted (e.g., modulating voices, removing identifying information like gender, date, location) to ensure you are not identified in any presentations. 15. 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. Res earch is a task that we perform in the public interest. Further information about your rights with respect to your personal data is available from the University’s Information Compliance web site at https://compliance.web.ox.ac.uk/individual - rights 16. Who has reviewed this research? This study has received ethics approval from a subcommittee of the University of Oxford Central University Research Ethics Committee. (Ethics reference: R87397/RE001 ) 17. Who is organising and funding the research? The University of Oxford is responsible for the design, conduct, and publication of results from this study. The present study is led by Dr. Min Gao and Dr Megan Kirk Chang from the Nuffield Department of Primary Care Health Sciences at the University of Oxford. The study is funded by the Oxford Health Biomedical Research Centre (OH BRC) led by Professor John Geddes based at the Oxford Health NHS Foundation Trust. 18. Who do I contact if I have a concern about the research or I wish to complain? In the very unlikely event that 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 with a member of the research team or contact DIMEStudy@phc.ox.ac.uk or telephone number 01865 289288 , and we will do our best to answer your query. Someone from our research team will acknowledge your concern within 10 working days and give you an indication of how it will be dealt with. If you remain unhappy or wish to make a formal complaint about this research study, you can 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 so on as possible. Email: ethics@medsci.ox.ac.uk or Address : Research Services, University of Oxford, Boundary Brook House, Churchill Drive, Headington, Oxford OX3 7GB 19. How have the public been involved in informing this study? People living with depression have been involved in the design of this study from the beginning. We asked them about questionnaire design, types of tests, and how to ensure the diet programme is successful. Th is public advisory group will provide regular feedback and guidance on study procedures as the study develops 20. Participation in Future Research Studies: We may want to see how participants in this study are doing in the future after the study period ends, or we may have other studies similar to this one that you might be interested in hearing about. If you agree, we may contact you in the future to ask whether you might be interested in being involved in another study. The research team would contact you to ask you about being involved, but by agreeing to being conta cted does not mean that you have to take part You can have your contact details removed from this register at any time by informing the research study team. If you agree to being contacted in the future, your contact details will be held securely , in a password - protected, encrypted folder, with restricted access, separate from any other data on a secure network at the University of Oxford. We will keep a copy of your consent form with this database, as your consent is our legal basis for re - contacting you under UK data protection law. 21. Further Information and Contact Details: If you would like to discuss the research with someone beforehand (or if you have questions afterwards), please contact: Dr. Min Gao or Dr. Megan Kirk Chang , DIME Study Coordinators Tel: 01865 289288 Email: DIMEStudy@phc.ox.ac.uk Thank you for taking the time to consider taking part in this study!