A double blind, randomised, parallel group placebo controlled study of cannabis based medicine extract (CBME) to validate the Neuropathic Pain Scale (NPS) compared with a single pain severity score, in central neuropathic pain in multiple sclerosis.
1. Purpose and Background
You are being invited to take part in a research study because you have the type of pain that the study is designed to treat. Before you decide whether to take part it is important for you to understand why the research is being done and what it will involve. Please read the following information carefully and discuss it with friends, relatives and your GP if you wish. This leaflet is for you to keep and explains what the study involves. Please ask us if there is anything that is not clear or if you would like more information. Take your time to decide whether or not you wish to take part.Introduction
Consumers for Ethics in Research (CERES) publish a leaflet entitled Medical Research and You. This leaflet gives more information about medical research and looks at some of the questions you may want to ask. A copy may be obtained from CERES, PO Box no 1365, London, N16 0BW.
You do not have to take part in this study, it is your choice whether you take part or not. You may leave the study at any time, without having to give your reasons for leaving if you do not wish to. Leaving the study will have no effect on the usual medical care you receive; you will continue to be treated by your doctor(s) as before. If you do leave the study after taking any study medicine we strongly advise that you return for the study doctor to give you a final medical examination. The South Sefton Research Ethics Committee have reviewed this study. The study will take place at The Walton Centre, Liverpool. We expect about 64 patients to take part in this study.
If you do decide to take part you will be asked to sign a consent form in which you agree to the provisions of this leaflet, including agreeing not to drive or take alcohol while under the influence of the study medicine. You will be given a copy of the signed consent form to keep. You will then have a medical examination and will be asked questions about your pain before the doctor makes a final decision about whether it is safe and wise for you to take part. We will inform your own GP and your Consultant, if you have one, before you start the study.
Although the use of cannabis is not permitted in the UK for medical or other reasons, it is widely known that some patients who take cannabis illegally find that it brings relief to certain types of pain or symptoms.
This cannabis medicine is currently being tested throughout the UK to treat pain and other symptoms. So far about 150 patients have received it. Five studies have also been completed in healthy volunteers and did not give rise to any safety concerns. In this current study we wish to find out if the cannabis medicine can help your pain and whether it works any better than the ‘placebo’, the dummy. The study medicine will have some side effects in at least some patients, and we will monitor these very carefully.
The cannabis medicine and the placebo are liquids, which are kept in a small pump-action spray similar in size and appearance to a breath freshener spray. When you take your first dose, at the hospital, a member of the study team will be with you. The medicine is taken gradually by spraying it a number of times under your tongue. The doctor or nurse will explain how to take your study medicine. Information that we currently have suggests that most patients symptoms get better at a much lower dose than would be needed to ‘get high’.
We will use one form of the cannabis medicine. This is made from the cannabis plants but contains different proportions of the main chemicals (cannabinoids) from the cannabis plant. The medication is called ‘1:1’, this contains equal amounts of two cannabinoids, THC and CBD.
You must bring all the medicine spray bottles, used and unused, to every study visit. A member of the study team will look at the number of doses you have recorded in the diary and how much medicine is left. If they think you have been recording the wrong amounts or that anyone else has had access to your medication they may have to ask you to leave the study.
There will be four parts to the study. When you come to see the study team you will need to be there for between 2 and 3 hours for Visits 1 and 3 and for up to 6 hours for Visits 2 and 4.
If you agree to join the study and sign the consent form at the back of this leaflet the study doctor will then ask you questions about your central neuropathic pain and medical history. The following list shows all the visits you will need to make if the results of your tests show you are suitable for the study and if you still wish to proceed.
You will visit the clinic. We will measure your; blood pressure, pulse rate, weight and perform a physical examination. We will take an ECG (recording heart activity), a blood and urine sample and a pregnancy test (for women only). Approximately 2 tablespoons full of blood will be taken for the blood sample. You will be asked to answer some questionnaires. You will be given a diary to complete for the next week (7 – 10 days) to record your daily pain. You will not be given any study medicine until the next time you visit the study team.
1 week later
You will visit the clinic. We will ask you to complete some questionnaires and assessments and we will check how your health has been. We will give you a dose of study medication and you will stay in the centre for the next few hours. You will be given study medicine to take home and new diaries. You will be given full instructions on how to take your medicine and complete the diaries. You will take the medicine and complete the diary for 1 week (7 – 10 days).
1 week later
You will visit the clinic. We will check how your health has been. We will check your medication and diaries. You will continue to take the medicine and complete the diary for a further 3 weeks (21 – 25 days).
3 weeks later or if you leave the study
You will visit the clinic. We will measure your; blood pressure, pulse rate and perform a physical examination. We will take an ECG (recording heart activity), a blood and urine sample and a pregnancy test (for women only). Approximately 2 tablespoons full of blood will be taken for the blood sample. We will ask you to complete some questionnaires and assessments and we will check how your health has been. This is the last visit. You will be thanked for your participation. You may be suitable for a longer term study, and should discuss this with your doctor. Your doctor will telephone in 30-40 days as a final check.
You may be given one of two study medicines, either ‘1:1’ or Placebo. Which study medicine you will receive is decided at random using a computer, like tossing a coin. Neither you nor the doctor will know which treatment you have been given, you may receive Placebo. If in an emergency, the doctor needs to know which treatment you are taking he/she can get this information from GW Pharma Ltd.
The Final Visit will be performed at the end of the study or if you leave the study early for any reason. This is for your safety, to check that there is no change in your condition, which had, so far, gone unobserved. This will be followed approximately 30 days later with a telephone call to further confirm that you have not experienced any ill effects.
At visit 4, or if you leave this study, the doctor may ask you if you want to enter a long term extension study. This will enable the doctor to provide the ‘1:1’ medicine to you on a long term basis if they think that you will benefit from its use. Currently, this is the only way to receive this medicine as it cannot be prescribed in the normal way. At the end of the extension study, it is uncertain whether the medication will be available for your doctor to prescribe to you. If you do not wish to receive the medication at any time, you should tell your doctor, who will discuss alternative treatments with you.
Study Card - You will be given a card stating that you are taking part in this study and you should carry this at all times.Potential Risks and Discomforts
Diary - You will be asked to fill in a daily diary of your pain and your use of the study medicine. The study team will show you how to complete it. If you are not sure, please ask them to explain again.
It is very important that you fill the diary in regularly and accurately. If you do not fill in the diary regularly the doctor may have to ask you to leave the study.
Test Medicine - It is always important to store medicines safely and out of reach of children but this is particularly important with cannabis-based medicines that could easily be misused. These medicines must be kept in the fridge. The research nurse will discuss storage with you. All test medicine units must be returned at each visit.
Other medicines - It is very important that you tell the study doctor at the beginning of the study which medicines you are taking, both prescription medicines and any you have obtained yourself and during the study to tell the study team of any changes. You will be allowed to keep taking your own medicines, including painkillers.
If you are taking cannabis at the moment you must tell us and stop it at least seven days before starting the study. You must agree not to use your own cannabis throughout the study. If you are found to have been using your own cannabis, we will ask you to leave the study.
Cannabis can affect almost all parts of the body and like any other drug may cause side effects. Cannabis has been used by people for different reasons for many hundreds of years and there have been no recorded deaths directly caused by cannabis alone, although some deaths have resulted from unwise use of cannabis with alcohol or with other drugs. The blood samples we ask you to provide, about a teaspoon full each time, may cause some discomfort and/or bruising.5. Potential Benefits
Possible effects - psychological effects: including ‘getting high’, this is not likely to occur with low doses and would not be expected to last very long if it does occur; change in how sharp your senses are (hearing and vision); drowsiness; changes in your ability to think; remember and to perform tasks, increased appetite and withdrawal effects. These are unusual, and would only be expected after heavy use. Other effects include palpitations; whites of the eyes becoming pink; coughing and airway obstruction, possibly only when cannabis is smoked, and decreased pressure in the eye. After using the spray, some patients may experience stinging or burning under the tongue.
The effects are likely to be mild and short-lived. If you are worried at any time by any effects contact the study team.
Driving and alcohol – cannabis based medicine may affect the ability to drive and operate machinery safely. You must not drive or undertake other potentially dangerous activities for the duration of the study. Alcohol may interact with the study medicine and produce a much more powerful effect than usual which can easily cause accidents in the home or elsewhere. You are strongly advised either to avoid alcohol for the duration of the study or use it very carefully in moderation.
Travel - You may not take your study medication outside the UK because cannabis is still illegal in many countries and you may be liable to prosecution in those countries. You cannot take part in this study if you plan to take a trip abroad during the period of the study.
Contraception - If you are part of a sexually active relationship the study doctor will ask you to take contraceptive precautions during the study and for three months after your last dose of study medicine unless you are female and are either not of childbearing potential or have been surgically sterilised. It is important that you try to avoid getting pregnant during the study because like most medicines, we do not have enough information to say cannabis medicines are safe in pregnancy. If you are a female and in spite of precautions you do become pregnant during the study or, if you are male, your partner becomes pregnant you must tell the study doctor immediately who will give you appropriate advice. If you are a female who is either pregnant, breastfeeding or planning pregnancy during the coarse of the study, you will not be able to take part in this study.
We know that many patients who use cannabis receive relief from pain and improvement in a wide range of other symptoms, often associated with improved sleeping and therefore a better quality of life. We hope this will be the case for you but, as is the case with many medicines, it is likely that not all patients will respond to the same extent. The information we obtain from your part in the study will help us to treat future patients more effectively.6. Alternative Therapy
There are some synthetic cannabinoids which can be prescribed but these are usually only for certain conditions and are not widely available. If the study medicine does not suit you, your own doctor will continue to discuss and prescribe alternative medication.7 .Travelling to the trial centre
If you think there may be problems with travel, please discuss them with a member of the study team before joining the study.8. Confidentiality and Data Protection
It is a requirement that your involvement in this study be noted in your medical records. Direct access to your records will be required by authorised representatives of GW Pharma Ltd to check the information collected for the study.
Your medical records may also be reviewed and copies made by members of the Independent Ethics Committee or a regulatory agency.
By signing the consent form, you (or your legally acceptable representative), authorise access to this confidential information.9. Compensation for Injury
Any information that you give before or during the study, including whether you have ever obtained cannabis illegally, will be kept in strict medical confidence. If results of the trial are published, your identity will remain confidential.
In order to comply with the UK’s Data Protection Act 1998 you must be informed that data collected during this study including your personal information will be reviewed, collected on a computer database and stored in an electronic, and/or manual files and could be reviewed, audited and processed by persons inside or outside the European Union including:
- Clinical Investigator.
- The study sponsor: GW Pharma Ltd or other persons authorised by GW Pharma Ltd.
The reasons why data is collected from your participation in the trial include:
- Regulatory and or other government agencies.
- Supporting the development of the study medicine.
- Supporting the licensing application for regulatory approval of the study medicine anywhere in the world.
All information relating to you collected whilst on the trial will not identify you by name but by an identity code and number and will be kept confidential and secure and will be used only for the purpose for which it was collected.
- To support the marketing, distribution, sale and use of the study medicine anywhere in the world.
The Home Office in the UK has licensed GW Pharma Ltd to conduct clinical research and the relevant authorities are fully aware of the research study. If you take part in this study you will NOT be taking cannabis illegally. If you take part in this study the Home Office will hold your name in strict security and confidentiality, in case they are asked to confirm that you are entitled to this medicine during the study.
GW Pharma Ltd, the sponsor of the study, will compensate you, according to The Association of the British Pharmaceutical Industry (ABPI) guidelines, for any reasonable medical expenses incurred (in excess of any insurance payments) for the treatment of any injury that is a direct result of the protocol. A copy of the ABPI guidelines is available on request. Any dispute as to the application of the above shall be referred to an arbitrator appointed by the Royal College of Physicians of London, with the power in the arbitrator to consult a barrister of 10 years standing with regard to the amount of compensation.10. Assurances
If you believe that you have a research-related injury, further information concerning the availability of compensation or treatment can be obtained from the study team.
If you have private medical insurance you may wish to check with your insurers that being in the study does not affect the conditions of your policy.
Dr Young, Dr Rog or GW Pharma Ltd may choose to withdraw you from this research study at any time.If you have any questions about the informed consent process or your rights as a research patient or you require any further information then you should ring the Walton Centre Clinical Trials Unit on 0151 5295666.
You or your legally acceptable representative will be kept informed in a timely manner of any information that may relate to your willingness to continue participation in the study. At the discretion of your doctor(s) and GW Pharma Ltd, you or your legally acceptable representative may be asked to sign a revised informed consent or consent addendum that provides this information.
You may ask questions at any time about this study. If you feel that you have experienced an adverse reaction to the study medicine(s) or procedures, or if you feel unusually unwell during the study, you should contact the study team.
Thank you for taking the time to read this information leaflet.