Effects of PR Oxycodone and of Levodopa, vs Placebo, on Central Neuropathic Pain in Parkinson's Disease

University Hospital, Toulouse67 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Parkinson Disease

Interventions

PR OxycodoneDRUG

PR Oxycodone

LevodopaDRUG

Levodopa

Oxycodone PlaceboDRUG

Placebo of PR Oxycodone

Levodopa placebo

Eligibility

Sex: ALLMin age: 40 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (18)

Hospital of Aix-en-Provence

Aix-en-Provence, France

CHU Amiens

Amiens, France

University Hospital of Bordeaux

Outcomes

Primary Outcomes

Average pain intensity

Change in average pain rated on visual analog scale (VAS) intensity between baseline and after 8 weeks

Time frame: 8 weeks

Secondary Outcomes

Maximal pain intensity

Change of maximal pain intensity over the preceding week rated on the VAS

Time frame: 8 weeks

Functional impact of pain" of the Brief Pain Inventory (BPI)