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MRC:LAMP STUDY
What is the purpose of the study?
We are looking at the effect lithium has on the way some parts of the brain work. Lithium is used in the treatment of mania, a psychiatric condition in which people have elevated mood, energy and increased activity. These symptoms may be due to a high levels of some brain chemicals such as dopamine. We suspect that lithium blocks the effects of dopamine.
Who are we looking for?
We are looking for 45 normal male volunteers to take part in the study. Volunteers should be fit and healthy without a history of psychiatric illness, and should not drink heavily or smoke to excess. If you fit these criteria, we would like to invite you to enter our study.
Do I have to take part?
No. As entry to the study is entirely voluntary, it is up to you to decide whether or not to take part. You should not feel under any pressure to make the decision. If you do decide to take part, you will be asked to sign a consent form but you are still free to withdraw at any time and without giving a reason. This will not affect any care you may receive in the future.
What will happen to me if I take part?
You will be invited to come to Newcastle Magnetic Resonance Centre to discuss the study in more detail. Here we will explain what we are doing, our reasons for conducting this study and answer any questions you may have. If you want to get involved we will set up some appointments for you to attend. These will all be within working hours, most probably in the morning.
What is the nature of the research?
Dopamine is important in causing the symptoms of mania, and we want to find out if lithium can block these effects. We can measure the effects of dopamine on blood tests, psychological tests and by using a brain scanner that measures brain function. As brain levels of dopamine can be temporarily increased by the administration of amphetamines, we can recreate some of the features of mania in the short term. We are measuring the effects of methamphetamine in subjects before and after treatment with various doses of lithium, as well as the effects of methamphetamine alone.
What will this study involve?
The initial assessment
You will be asked to come to Newcastle Magnetic Resonance Centre for a routine assessment where we will conduct a series of questionnaires designed to exclude mental illness and symptoms of depression or mania (assessments performed by Dr David Cousins). We will do a brief external physical examination and some blood tests to make sure that it's safe to go ahead with the study.
We will introduce you to the psychological tests. These are designed to test your concentration, attention and some aspects of memory (immediate recall of information). They involve watching a series of numbers or letters on a computer screen and responding to certain patterns and combinations according to instructions you are given. You will need to practice this twice on your first visit.
This visit should take about two ours in total
The next stage
The testing of brain functioning
We will begin by repeating the psychiological tests.
Cannulation
After this practice we will insert an intravenous cannula, a small tube that goes into a vein and allows blood to be taken and injections to be given. This causes minor discomfort only. After taking some blood samples from this cannula, the brain scanning session will begin.
Blood tests
We will use your blood sample to assess the effects of methamphetamine on aspects of dopamine activity. In order to interpret the effects of the medications, the psychological tests and the MRI results it helps to know information about your genetic make-up. We would like to test for the presence and type of certain genes involved in the action of dopamine. These results will remain confidential, are not a full “genetic fingerprint” and cannot be used for any purpose other than research. However, the sample may be stored for similar analyses in the future. Testing for certain genes will be done only with your consent, and seperate permission and consent will be sought for storage of a sample. If you do not wish to provide such a sample, you can still take part in the rest of the study.
Brain scanning
When you have practiced the psychological tests, we will repeat them while you are having a brain scan. This will involve lying down in the MRI scanner for about ½ hour. The scanner is an enclosed tube that some people find results in a sense of claustrophobia. If you know that you suffer from claustrophobia then you should not volunteer for this study. It is also quite noisy though generally not unpleasant. If you become uncomfortable, you can let us know and we will stop the scan immediately.
Amphetamine
After the first scanning and testing session, you will come out of the MRI machine briefly in order to receive the dose of methamphetamine as an injection. Methamphetamine injection is associated with a sense of mild euphoria and a ‘buzz’. The dose we are using is relatively small and is just sufficient to cause the effects we are studying. You may, however, feel restless particularly on returning to the scanner. We will repeat the scanning procedure and psychological tests immediately following injection. This should take approximately ½ an hour.
Observation in the centre
Although complications of methamphetamine administration are unlikely, it is a requirement that we observe you for a number of hours following the injection. A doctor will be present on site throughout this time should you require assistance. We advise that you bring a book to read, or similar distractions. At the end of the day we can arrange for a taxi to take you home if required.
Randomisation
Volunteers will be randomly assigned to one of 3 groups; a) lithium treatment in a dose for mania, b) lithium in a dose for prevention of mania or c) placebo (“dummy tablets”). You will not know which group you have been allocated to, but some members of the research team will.
Lithium prescription
We need subjects to take lithium for one week at the correct dose before we can repeat the brain scan. Lithium takes a short while to get into your body and reach the correct level, and this level can be checked with a blood test. We will give you a starting dose based on your age, weight and blood tests, and ask you to return after five days treatment for a blood test. If that blood test is ok, you will be asked to keep taking that dose for about seven days before coming back. If the blood level is not spot-on, the dose will be changes and checked again. When the correct dose is reached, you will continue at that dose for seven days until rescanning. We usually get the dose correct on the first attempt.
At the end of the treatment period, the scanning procedure will be identical to that described above, and will involve an injection of methamphetamine as outlined.
What are the effects of Lithium?
The dose of lithium we are using in this study has been proven to be safe in previous studies. You may have some mild side effects such as sickliness or tiredness. If you develop side effects such as tremor, excess sleep or thirst, you should contact us or your family doctor. We will give you a list of things to look out for and instructions if problems arise.
What are the effects of amphetamines?
Methamphetamine can reproduced the symptoms of mania, and you may feel a little elated, full of energy or experience of “buzz”. You may also be restless following the injection. There is a very slight chance that methamphetamine can trigger mania itself. The research team has previous experience of administering methamphetamine and has observed no such adverse reactions.
What are the advantages of taking part?
Your participation is unlikely to benefit you directly. It is hoped that the information that this study provides will help us the understand more about the nature of mania and its treatments. You will get to see you brain however!
Will I be paid?
No, but we will compensate you for your travel and time. We are currently reimbursing subjects at a flat rate of £100.
What if something goes wrong?
If you are harmed by taking part in this research project, there are no special compensation arrangements to cover non-negligent injury. If you are harmed due to someone’s negligence, then you may have grounds for a legal action but you may have to pay for it. Regardless of this, if you wish to complain, or have any concerns about any aspect of the way you have been approached or treated during the course of this study, you should approach the NewcastleUniversity for advice.
Will my participation be confidential?
We will hold some personal information on file at the Newcastle University. Your personal details will not be routinely available to the researchers as all forms will be completed using an anonymised personalised identification number. Only the university staff directly involved with the research will have access to your details.
We are obliged to inform your GP about your participation in the research, and will ask your permission before we do so.
What will happen to the results of the research?
After the study is completed, we will analyse the results and submit them for publication in a scientific journal. Presentations may also be given at scientific conferences. You will not be identified in any publication or presentation. If you wish to know the outcome of our research, we will be happy to discuss them with you.
Who is organising the research?
The principal investigator is Dr David Cousins from the Newcastle Magnetic Resonance Centre. The research is publicly funded by a grant from the Medical Research Council and is under the supervision of Professors Andrew Blamire and Nicol Ferrier.
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