effects of pr oxycodone and of levodopa, vs placebo, on central neuropathic pain in parkinson's disease

Conditions: Parkinson Disease

Summary: this study will be conducted in three parallel groups receiving oxycodone, levodopa or placebo, administered as an add-on therapy, in addition to the usual antiparkinsonian treatment. as this study focuses on chronic central neuropathic pain caused by pd, the effects of study treatments will be evaluated after a 10-week treatment period

the treatment period (11 weeks) will be divided into three periods: 1. a titration phase of two weeks, during which of the doses of the treatments will be gradually increased in three steps: level 1 (from d1 to d5): * oxycodone: 10 mg pr/day bid (5 mg pr/5 mg pr) * levodopa: 100 mg/day bid (50 mg/50 mg) level 2 (from d6 to d10): * oxycodone: 20 mg pr/day tid (10 mg/0 mg/10 mg) * levodopa: 150 mg/day tid (50 mg/50 mg/50 mg) level 3 (from d11to d15): * oxycodone: 40 mg pr/day tid (20 mg/0 mg/20 mg) * levodopa: 200 mg/day tid (100 mg/50 mg/50 mg) 2. a fixed dose period: the level 3 dose will be maintained for 8 weeks (from d16 to d71). the study treatment will be administered as an add-on therapy, with the usual antiparkinsonian treatment. if patients have side effects at the level 3 dose, a return to the level 2 dose will be authorized. 3. a withdrawal period: the dose of the study treatment will gradually be reduced, over an eight-day period: for patients treated with the level 3 dose for 8 weeks: decrease to the level 2 dose over the first 3 days (from d72 to d74) ; then a decrease to the level 1 dose over the next 3 days (from d75 to d77). the treatment will be stopped completely on d78. the last visit will take place on d79, 2 days after the end of treatment. for patients treated with the level 2 dose: decrease to the level 1 dose over the first 3 days (from d72 to d74), with stopping of the treatment on d75. the last visit will take place on d79, 5 days after the end of treatment.

Eligibility criteria:
inclusion criteria: * patients with parkinson's disease according to the ukpdsbb (united kingdom parkinson's disease society brain bank) criteria * patients suffering from chronic pain (lasting for more than 3 months) * patients suffering from central neuropathic pain caused by pd, * patients with a pd-related central neuropathic pain intensity of at least 3 points on the vas (average intensity over the last month), * patients with both types of pain (neuropathic and nociceptive) will be included if the neuropathic pain predominates * patients treated with a stable regimen of dopaminergic drugs (levodopa and/or dopamine agonists) for at least 4 weeks before the study dan throughout the study * patients with a stable step 1 analgesic (nsaids, acetaminophen) or coanalgesic (antidepressants, antiepileptic) treatment for at least 4 weeks before the study and throughout the study exclusion criteria: * patients suffering from another parkinsonian syndrome * de novo patients (patients never before treated with dopaminergic drugs) * patients with intercurrent acute pain * patients suffering from a chronic disease causing pain (rheumatoid arthritis, ankylosing spondylitis, diabetic neuropathy, cancer etc.) * patients treated with neuroleptics * patients with clinically detectable behavioural disorders and addiction * patients with disabling dyskinesias * patients with painful restless legs syndrome * patients with cognitive impairment (mms \< 25) or unable to complete the various scales used in the study * hypersensitivity to oxycodone, levodopa, benserazide or a combination of these drugs * patients treated with opioid drugs (step 2 and 3) * patients treated with non-selective monoamine oxidase inhibitors (maoi) * patients with severe hepatocellular insufficiency * patients with uncontrolled cardiovascular and pulmonary diseases * persistent constipation that has already resulted in a subocclusive state * patients treated with antiemetic neuroleptics * patients with angle-closure glaucoma exclusion criteria relating to mri: * patients with claustrophobia * patients with a hearing aid, cardiac prosthesis, pacemaker, surgical clip * patients refusing to be informed of abnormalities are detected on mri