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ReD-KITEResistant Depression – Ketamine Infusion Trial Evaluation
Stage 1
PARTICIPANT INFORMATION SHEET
We would like to invite you to take part in our research study.
Before you decide, we would like you to understand why the research is taking place and what it would involve for you.
Please take the time to read the following information carefully, and discuss it with family, friends and your GP if you wish. We will then go through the information with you and answer any questions you have. This will take about 20 minutes.
Part 1 tells you about the purpose of this study and what will happen to you if you take part.
Part 2 gives you more detailed information about the conduct of the study. Please keep the information in case you wish to refer to it later.
Part 1
What is the purpose of the study?
The purpose of this study is to investigate the safety of the drug ketamine as a treatment for people with depression who have not responded to other treatments.
Previous studies in people with this sort of depression have found that a one-off treatment with a low dose of ketamine, given intravenously, can lead to an improvement in mood, lasting up to 7 days. This study investigates whether the same dose of ketamine can be safely repeated and whether the beneficial effect is sustained with repeated treatment.
Why have I been invited?
You are being invited because you are currently being treated for a depressive illness and have already tried antidepressant medication but remain depressed. Your psychiatrist or GP may be considering further treatment options for you.
Do I have to take part?
No. It is entirely up to you to decide whether or not to take part in the study. If you do agree to take part, we will then ask you to sign a consent form. However, you are free to withdraw at any time, without giving a reason.
What will happen if I take part and what will I have to do?
Summary:
A researcher will arrange to visit you to explain the study, go through what is involved, answer questions, and make sure you are eligible to take part in the study.
The treatment involves having a needle put into a vein on the back of your hand and a low dose of ketamine infused over 40 minutes. This happens once a week for three weeks at the WarnefordHospital in Oxford.
You will stay in the clinic for about 3.5 hours. During this time, the researcher will ask about your symptoms. Later in the afternoon, when you have returned home or, if you are an inpatient, to the ward, (s)he will visit again and ask about your symptoms. (S)he will also visit you to ask about your symptoms on the day before each treatment and at 1, 2, 4, 8 and 12 weeks after the last ketamine treatment.
As part of the follow-up process you will also be asked to complete a symptom questionnaire (True Colours) via text or email if feasible. This will take a few minutes to complete. We would like you to complete this:
Daily for the first 3 weeks,
Then 2 x a week for the following 3 months,
Then 1 x a week for the following 3 months.
In total, your involvement in the study will last 6 months 3 weeks.
If you do not have access to text or email, this will NOT exclude you from the study.
Detailed schedule
Visit 1. Screening
A researcher, who may be a nurse, psychologist or doctor, will visit you to explain the study, go through what is involved, answer questions, and make sure you are eligible to take part in the study. You will then be asked to read and sign a consent form. Although by signing this you indicate that you agree to take part, you can withdraw at any point without giving a reason.
(S)he will then ask you about the history of your depression and other illnesses and about your current symptoms. (S)he will ask you to complete various questionnaires and willdo some memory tests, including some which involve thinking about your past.
The researcher will take a blood sample to make sure that you do not have any physical illnesses which would mean that you could not take part. (S)he will take your pulse, blood pressure and temperature. A doctor will do a physical examination.
This visit will last about 2 hours. All the visits except the treatment sessions will be at your home or at the hospital, depending on your circumstances and wishes.
Visit 2. Baseline
On the day before your first ketamine visit, the researcher will visit you again. (S)he will repeat one of the tests, ask about your symptoms and do some more memory tests. This visit will take less than an hour.
Visit 3. First treatment
On the day of your first ketamine treatment you will come to the clinic at 8.30-9am. You may have a light breakfast before.
A consultant anaesthetist will put a needle into a vein on the back of your hand and set up a drip so that a low dose of ketamine is gradually infused over 40 minutes.
During this time, you will be able to lie down or sit in a chair. A researcher will remain with you. You will not need to get undressed. Before, during and after the infusion a researcher will check how you are feeling and ask you to describe and record any symptoms or side effects you may be experiencing.
You will stay in the clinic for about 3.5 hours. After that, you will be able to go home or to the ward when you feel well enough to return. Later that afternoon, at about 3pm, you will be visited at your home, or on the ward if you are an inpatient, by the researcher who will ask about your symptoms again.
1 and 3 days later, a member of the team will telephone you briefly to assess side effects and mood.
For 3 weeks starting on visit one you will be asked to complete a symptom questionnaire via email or text (if feasible) daily. This will take a few minutes.
Visit 4. Follow-up
Six days later, the researcher will visit again to review your progress and to ask about your symptoms. This will take less than 30 minutes.
Visit 5. Second treatment
The following day (i.e. a week after your first treatment), you will come to the clinic again. The procedures will be the same as for the first treatment (Visit 3).
Visit 6. Follow-up
Six days later, the researcher will visit again to review your progress and to ask about your symptoms. This will take less than 30 minutes.
Visit 7. Third treatment
The following day (i.e. a week after your second treatment), you will come to the clinic again. The procedures will be the same as for the previous two treatments (Visits 3 & 5).
After you have received the third dose of ketamine you will have completed the treatment part of the trial.
If you are not scheduled to see the doctor who is treating you for your depression within the 2 weeks after the final treatment, then a study doctor will review you at this point and write to your doctor.
If ketamine has had a positive effect on your mood, your doctor may consider some of the following treatments which may be able to maintain this improvement.
- Memantine, a drug originally used in Alzheimers Disease, but which works in a similar way to ketamine.
- Maintenance ketamine treatments (once every 1-3 weeks).
- Prescribing a new antidepressant.
- A further course of ketamine injections.
If you receive extra ketamine infusions, you will be monitored for 6 months following your last ketamine infusion.
Visits 8-12
After the treatment phase of the study you will be visited to review your progress and to fill in appropriate questionnaires. These visits will take place 1, 2, 4, 8, 12 and 24 weeks after the last ketamine treatment.
From one week after the treatment phase you will be contacted twice a week for 3 months via text or email and asked to complete a questionnaire. The questionnaire should take a few minutes to complete.
After this time you will then be contacted once a week to complete the same questionnaire for a further 3 months.
Expenses and payments
If you or your family incur travel expenses within the UK as a result of you taking part in the study, these will be reimbursed. Text costs from completing study questionnaires will also be reimbursed. No other payments will be made for taking part in this trial.
What is the drug being tested?
Ketamine is widely used in general hospitals across the world as an anaesthetic. The dose of ketamine used in anaesthesia is higher than the dose being used in this study. Repeated doses of high doses of ketamine are commonly given. In some centres, ketamine is given repeatedly to patients with depression who are having electroconvulsive therapy.
In the low dose which will be used in this study, ketamine has been shown to lead to short term improvements in mood, lasting up to 7 days, in individuals with depression which has not responded to treatment.
What are the side effects of treatment received when taking part?
At high doses, ketamine commonly causes brief side effects including feeling ‘spaced out’ or drunk. Patients sometimes report that ‘things look peculiar’ or have hallucinations. Sometimes patients feel sick. At high doses these effects sometimes continue for a few hours.
Ketamine is sometimes used as a drug of abuse because of the effects it has at high doses. It is not addictive.
In the studies of low dose ketamine use in patients with resistant depression, more mild symptoms of feeling ‘spaced out’ or drunk, or of visual distortions also sometimes occur. They last no more than 90 minutes.
What is not known is whether, using repeated low doses of the drug, these symptoms cause significant distress and whether they get better, remain unchanged or get worse during each successive treatment. We also do not know whether any benefit is more sustained after repeated treatments than after a single treatment.
The treatment involves having a needle put into a vein on the back of your hand and a low dose of ketamine infused over 40 minutes. As a result, there is a chance that temporary bruising may occur at this site.
What are the possible disadvantages and risks of taking part?
The main risk is of the side-effects described above.
Your GP or psychiatrist may alter your other medication while you are taking part in the study. If the ketamine seems to improve your mood during the study but worsened again after the end of the trial, your participation might have resulted in a delay in such changes to your medication or other treatments.
Ketamine is not known to interact with antidepressants or other psychiatric medication.
What are the alternatives for treatment?
Your psychiatrist or GP may have discussed possible alternative treatments with you. These are likely to include further drug treatment including antidepressants or possibly electro-convulsive treatment (ECT), and may also include some form of talking therapy.
What are the possible benefits of taking part?
Although earlier studies have identified short term improvements in mood after taking ketamine it is not possible to be sure that improvement in mood will occur in all cases. Neither is there any certainty that any improvements will be maintained.
Participation in the study will lead to new information which could lead to better treatment for other patients in the future.
What happens when the research study stops?
After the treatment phase of the study, your doctor will discuss further treatment options with you. These may include further drug treatment including antidepressants or possibly electro-convulsive treatment (ECT), and may also include some form of talking therapy.It will be up to you and your own doctor to decide what treatment would be appropriate.
What if there is a problem?
Any complaint about the way you have been dealt with during the study or any possible harm you might suffer will be addressed. Detailed information about these processes are given in Part 2.
Will my taking part in the study be kept confidential?
Yes. We will follow ethical and legal practice and all information about you will be handled in confidence. The details are included in Part 2.
ReD-KITEResistant Depression – Ketamine Infusion Trial Evaluation Stage 1
PARTICIPANT INFORMATION SHEET
Part 2
What if relevant new information becomes available?
If this happens, your research doctor might consider you should withdraw from the study. He will explain the reasons and arrange for your care to continue.
What will happen if I don’t want to carry on with the study?
You are free to withdraw from the study at any time simply by telling the researcher or a member of your clinical team that you wish to do so. If you withdraw, we will still need to use any information or data given to us before your withdrawal. Your further treatment would then be agreed with your doctor and clinical team in the usual way. With your explicit permission, we would like to keep in contact with you to see how you get on after leaving the study.
What if there is a problem?
If you have a concern about any aspect of this study, you should ask to speak to the researchers who will do there best to answer your questions. You can contact them by ringing on the numbers given below. If you remain unhappy and wish to complain formally you can do this by contacting the Patient Advice and Liaison service at the WarnefordHospital. You can contact them by ringing 01865 223752 or by visiting their office at the front of the Warneford (Mon 2-5pm, Tues 9.30-12.30, Wed 2-5pm, Thurs 9.30 -12.30 and Fri 9 -12pm.) Alternatively, complaints can be made in writing to the Complaints, PALS and Legal Services Department at the WarnefordHospital, Old Road, OxfordOX3 7JX.
In the event that something does go wrong and you are harmed during the research trial and this is due to someone’s negligence then you may have grounds for a legal action for compensation against Oxford Health Foundation NHS Trust but you may have to pay your legal costs. The normal National Health Service complaints mechanisms will still be available to you (if appropriate). As legal sponsor of this study, Oxford Health NHS Foundation Trust will give sympathetic consideration to claims of non-negligent harm suffered by a person as a result of the study. The Trust effectively acts as its own insurer with backing from HM Treasury and does not provide cover for non-negligent harm in advance for participants in Trust sponsored studies. Where studies are carried out in a hospital, the hospital continues to have a duty of care to a patient being treated in the hospital, whether or not the patient is participating in a trust supported study.
Will my taking part in the study be kept confidential?
All information which is collected about you during the course of the research will be kept confidential. If you take part in the study you will be assigned a code number that will be used to identify you on all computerised and written data. Your name, and any other identifying information, will not be attached to the information obtained from the study. All personal data will be kept securely in locked filing cabinet with access available only to members of the research team. Electronic anonymised data will be kept in password protected files and will be stored securely. Data will be kept for no more than 15years and will then be destroyed.
Data that is obtained by the True Colours team (text and email questionnaires) will be stored on a secure database which can be accessed only by authorised members of the True Colours team. This anonymised data may be made available in research intended to improve the treatment of mood disorders and the promotion of good mental health. Any research use of the data will be ethically and scientifically approved.
Involvement of General Practitioner/Family Doctor (GP)
With your permission your GP will be informed by letter about your involvement in the trial and the trial medication you will receive.
What will happen to any samples I give?
The blood sample you give at the beginning of the trial will be destroyed after it is analysed.
What will happen to the results of the research study?
The results of this study will be reported in scientific journals and are likely to be published after the whole study finishes in 2012. You can obtain a copy of the published results by contacting us at address on the bottom of this sheet after the study has finished. You will not be identified in any report or publication resulting from this study.
Who is organising and funding this research?
This study is being undertaken by Dr Rupert McShane, Consultant Psychiatrist. It is sponsored by the Oxford Health Foundation NHS Trust. It is funded by the NHS National Institute for Health Research (NIHR) Research for Patient Benefit Programme and is being carried out with the support of the Oxford Clinical Trials Unit for Mental Illness (OCTUMI).