Extrait

Background and study aims Levodopa (Sinemet or Madopar) is the main treatment for Parkinson’s disease (PD). In the brain, levodopa is transformed into dopamine, the brain chemical whose levels are reduced in patients with PD. Unfortunately, after a few years of therapy patients develop troublesome involuntary movements known as dyskinesias. It is not clear what causes these involuntary movements and at present, there are few effective cures for treating them once they have developed. In this project we will explore a possible mechanism responsible for the Levodopa-induced dyskinesias. We believe that another brain chemical called serotonin may interfere with the transformation of levodopa into dopamine and this may cause or aggravate these involuntary movements. At the Cyclotron Building, Hammersmith Hospital in London we perform special types of brain scans which can be used to measure chemical changes within the brain and consequently study the functions of the brain. These scans are called positron emission tomography (PET) scans. In this study we will use a PET scan to evaluate how serotonin affects the production of dopamine in the brain after a single administration of oral levodopa (namely a tablet of Sinemet). This information may help us to treat PD patients with dyskinesias better. Who can participate? In this project we are studying patients suffering from Parkinson’s disease with and without dyskinesias. What does the study involve? In this study two groups of PD patients will be studied: PD patients suffering from dyskinesias and/or motor fluctuations and PD patients without dyskinesias and/or motor fluctuations. The study will be conducted in two parts, and we will ask you to attend the Hammersmith Hospital for a total of 5-7 separate days. All visits will be on a weekday morning, and taxi transport will be provided. According to the type of anti-parkinsonian or other medication you are on, we will ask you NOT to take it overnight or on the morning of your visit. In the first part, at the first visit we will enquire about the progression of your Parkinson’s disease and your medication history. We will perform a clinical examination to assess the severity of your symptoms (e.g. tremor and stiffness) when you are off medication. This clinical examination is very similar to those you have during Neurology clinic appointments. We will evaluate the presence of depression by asking you to fill in a questionnaire. We will ask you to take a tablet of levodopa and will observe for improvement in your symptoms and perform regular clinical exams (every 15-25 minutes), and note the presence and severity of dyskinesias. This visit will last about one and a half hours. PD patients with dyskinesias and/or motor fluctuations will also attend a second visit, at which we will ask you to take a tablet of levodopa plus tablets of Buspirone. Buspirone is a medication currently licensed in UK for mild anxiety and has been shown in a previous research study to decrease the level and intensity of dyskinesias. We will observe with repeated clinical examinations (one every 15-25 minutes) how your symptoms and the severity of dyskinesias improve over the next one and a half hours. We expect that you will have less dyskinesia. Some of the results from part one will be compared with the PET scan findings to investigate their relationship with chemical changes within the brain. In the second part of the research project, we will use PET scans to measure chemical changes within the brain areas known to play a role in PD and in the development of dyskinesias. You will undergo four different types of PET scans on four separate visits. In one of these visits, we will collect a blood sample (10 ml blood sample = two teaspoons) to investigate the presence of a gene related to depression and to serotonin. Each PET scan takes from 1 hour and 20 minutes up to 1 hour and 50 minutes (provided if there are no delays). During this time you will be asked to lie on your back on a couch with your head resting in the scanner. You may listen to music or the radio during the scan. Prior to the scan we will insert a small tube (cannula) into a vein in your arm. This is a simple procedure similar to a blood test. We will inject a small amount of radioactive compound (called a tracer), which is taken up by specific areas of the brain that we intend to investigate. One PET scan will be performed after you have taken a tablet of levodopa given at the hospital site. Another one will be performed after taking both Sinemet and Buspirone. The remaining two scans will be performed in an OFF medication state. In addition, we will ask you to undergo a magnetic resonance scan (MRI). This provides a detailed structural picture of the brain and does not involve any additional radiation. This scan takes about 15 minutes. We will endeavour to perform this on the same day of one of the PET scans. If you are claustrophobic you may find MRI difficult to tolerate, if so please let us know in advance. What are the possible benefits and risks of participating? There will be no direct benefit for you taking part in this study. However, by conducting this study we hope to learn more about dyskinesias in PD and the role of Buspirone. In addition, this information may help us to improve the treatment of these common problems. The placing of the cannula into a vein may cause some transient, mild discomfort and local bruising. The radiation dose you will receive by having this PET scan is about four times the background radiation dose to which we are all exposed every year simply by living in the UK. Along with other procedures involving radiation (including x-rays), PET scans can be hazardous to an unborn child. If you are a woman of child-bearing age you should not take part in the study unless you are on a reliable form of contraception, and even if this is the case a pregnancy test will be performed before the PET scan. When you are off medication, your Parkinsonian symptoms, such as difficulty in movement, will be transiently worse. In particular, you may feel stiffer, especially if your Parkinson’s disease is well established with stiffness rather than tremor being your main symptom. However, your symptoms will recover to their usual level as soon as you take your usual medication immediately after the PET scan. You should be aware that there is a possibility that the methods used in this study may produce an unexpected result that may have relevance for your health. In the unlikely event of this happening, we will discuss this with you and, if necessary, provide any support that you may require, such as arranging follow-up tests and/or treatment. Where is the study run from? Hammersmith Hospital, Imperial College London (UK). When is study starting and how long is it expected to run for? The study will run from January 2008 to January 2014. Who is funding the study? The Michael J Fox Foundation for Parkinson's Research. Who is the main contact? Dr Marios Politis [email protected]

Critère d'inclusion

• Parkinson's disease

Liens

• isrctn
• ictrp