Appendix 15: LPC Website The Painful Channelopathies Study is an initiative of the Wellcome Trust funded LONDON PAIN CONSORTIUM to try to understand the mechanisms of pain in genetically determined conditions. You are being invited 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 time to read the following information carefully and discuss it with others if you wish. What is the purpose of this study? You have been invited to take part in this study because you either experience increased or reduced pain which may have unusual characteristics and could be an inherited condition. Little is currently known about the characteristics of sensory disturbance and brain activation responses in patients with inherited pain syndromes. These can cause either increased or reduced sensation of pain in affected individuals. Some such pain syndromes have been classified and given names such as:
Erythromelalgia, Paroxysmal extreme pain disorder, Familial episodic pain syndrome and Congenital insensitivity to pain.
There are other pain syndromes that have not been clearly classified. This study is designed to better understand what causes these changes in sensation and the consequences of such changes for patients. This will include investigation of the specific genetic changes associated with inherited pain syndromes as well as the changes in sensory processing and brain activity. The study involves you filling in questionnaires, undergoing detailed neurologic and sensory testing of your skin, the taking of a small skin biopsy, a blood sample and a magnetic resonance scanning of the brain. Does this study concern me? If you have an alteration in pain sensation and there is a possibility that this may be genetic as the same condition has affected previously other of your family members, you may consider to participate in this study. What will happen to me if I take part? If you are interested in taking part in the study, an appointment with a researcher will be made at a time convenient for you. The study is completed in 1 or 2 appointments: Guy’s Hospital Campus, London (How to get there: http://goo.gl/maps/Chy0f ). FMRIB Centre at the John Radcliffe Hospital, Oxford (How to get there: http://goo.gl/maps/uNT2t ).
Appendix 15: LPC Website During these appointments you will be able to ask any further questions that you may have regarding the study. We will also check if you are eligible for the study. If you wish to take part in the study, you will be asked to sign a consent form and given: 1. Questionnaires:
A simple diary in which we would like you to record your daily (if any) pain twice a day for 7 days.
A questionnaire about you, your past medical history, medications you are or have been taking,
5 questionnaires, which will take approximately 1 hour to complete will ask you about the impact of any pain you have, has on your mood, sleep and quality of life.
2. Blood Sample: We will take a blood sample. DNA will be extracted for genetic studies and this sample will be stored in locked freezers located at King’s College London and University College London. Genetic analyses will be strictly restricted to causes of altered pain sensation, all samples will not have your name, address or any other label from which you could be identified. In the future as new genes are discovered we may collaborate with other research groups around the world which may involve sending these anonymised research samples to other laboratories. Because these tests are performed on a research basis and can’t yet predict the risk of developing pain on an individual basis you will not receive these results. In certain clinical conditions genetic testing is available as a clinical service in which case we will inform you of where this service is if you would like to consider formal genetic testing. In addition during the research appointment a researcher will review your medical notes. These details will remain anonymous all the time and will not be shared under any circumstances. 3. General Neurological Examination: We will examine you clinically for muscle strength, reflexes and changes in your skin’s ability to feel different stimules in your arms and legs. We will also measure your weight, height, and blood pressure. 4. Quantitative Sensory Testing of both feet: This is a more detailed method of testing the function of the small sensory nerve fibres in your skin, which detect changes in temperature, pressure, sharpness and touch. It is in routine diagnostic use in our clinic. Your ability to sense changes in temperature is determined using a small probe applied to your skin which changes temperature, i.e. becomes cool or warm. You will be asked to say when you can feel any change.
Appendix 15: LPC Website Your ability to detect light touch is determined using very fine filaments, again you will be asked to say when you can feel them. For sharpness a small probe designed not to puncture the skin, is applied to your skin. You are asked to say when it begins to feel sharp. A blunt pressure gauge is used to apply pressure. You will be asked to say when the pressure just begins to become uncomfortable. We will also lightly touch a small area of your skin with a Q-tip, cotton wool, a paint brush and a tuning fork and ask you to describe the sensation that you experience. Some of these tests may cause slight discomfort, however you will be able to stop at any point if you are not happy. 5. Skin Biopsy: You can still be included in the study if you decline this investigation (a picture of skin biopsy). A very small: 3 or 4 mm (~1/10 inch) circular piece of skin (skin biopsy) will be taken. A single suture may be required following the procedure. The sites from which the skin biopsy is likely to be taken are the lower leg, the arm or the scalp. A small plaster will be applied and an ointment will be provided to keep it clean afterwards. Sometimes a small suture is needed in which case you can either attend your GP to have it removed or you can also come to us. This procedure is routine practice in dermatology clinics and is being increasingly used in pain and neurology clinics. We are highly experienced in this technique. There is a low risk of infection, scarring and reduced hair growth at the site of the biopsy. Healing usually occurs in 7-10 days. This skin biopsy will then be examined under a microscope to determine the degree of small nerve fibre damage (if present) in your skin. We will also keep the remaining unused tissue in a locked freezer at King’s College London for future biochemical analysis investigating channelopathies and pain. In some cases cells will be extracted from the skin biopsy and grown in the laboratory prior to being stored in a locked freezer. They will be studied in the future to try and understand how genetic changes in cells cause altered pain sensation. To study theses cells they may be transferred to collaborators at other institutions outside of King’s College London such as Newcastle University. The samples will not have your name, address or any other label from which you could be identified. 6. Magnetic Resonance Scanning: You can still be included in the study if you decline this investigation. This procedure is called functional magnetic resonance imaging (FMRI). This is a safe technique that is performed routinely and allows an insight in the brain processing of stimuli. This method is a safe and non-invasive technique and does not carry radiation risks. MRI scans will be carried out by trained MR technicians at the FMRIB centre of the University of Oxford (www.fmrib.ox.ac.uk).
Appendix 15: LPC Website During the experimental acquisition of data, the skin temperature of the patients may be externally adjusted to trigger some features of pain crisis or to provide relief, temperature changes can range from 5°C to 40°C. This method accompanied by the real time scanning of cerebral responses will provide invaluable information about the determination of the origins of pain. The procedure is extremely safe, and only causes mild discomfort. You are also able to take breaks, for whatever reason, at any point during the study if you wish. What are the possible disadvantages and risks of taking part? The main disadvantage is that you will need to give up some of your time to take part. Another disadvantage is that you will be required to travel to one of the study sites (either King’s College London, London or John Radcliffe Hospital, Oxford) for an appointment. We will reimburse your travelling expenses if required. What are the possible benefits of taking part? We cannot promise the study will help you, but the information we get might help improve the treatment of people with altered pain sensation. We will get more information about how your sensory nervous system works and if you are in agreement we will send information about the skin biopsy analysis and the quantitative sensory testing to your doctor. At the end of the study we hope to: 1. Identify the specific impact of different aspects/ components of pain on quality of life and psychological well being. 2. Find the brain areas involved in the central processing of pain. 3. Our hope is that through a greater understanding of the genetic changes causing these conditions and the effects that they have on the processing of sensation we will be able to develop better treatments for pain in the future. Will my taking part in this study be kept confidential? All information that is collected about you during the course of the research will be kept strictly confidential. We will store data from these studies into research sites computers for analysis and also include it in computer databases which are used to store and analyse data about channelopathies and pain; these are the Wolfson CARD, King’s College London, the Wolfson Institute for Biomedical Research at University College London and the FMRIB at John Radcliffe Hospital, Oxford University. By comparing the information from this research with that from other studies we will be able to learn more about these conditions.
Contact for Further Information:
Appendix 15: LPC Website
For further information regarding this study please contact: Dr Juan D Ramirez Rozo Tel 07902 114851- 02078486184 or email: [email protected]