Effects of PR Oxycodone and of Levodopa, vs Placebo, on Central Neuropathic Pain in Parkinson's Disease
- Conditions
- Parkinson Disease
- Interventions
- Registration Number
- NCT02601586
- Lead Sponsor
- University Hospital, Toulouse
- Brief 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
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 67
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description levodopa Oxycodone Placebo A titration phase of two weeks, in three steps: Level 1 (from D1 to D5): * Oxycodone placebo : 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 placebo: 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 placebo: 40 mg PR/day tid (20 mg/0 mg/20 mg) * Levodopa : 200 mg/day tid (100 mg/50 mg/50 mg) * A fixed dose period: the level 3 dose will be maintained for 8 weeks (from D16 to D71). * A withdrawal period: Placebo Oxycodone Placebo A titration phase of two weeks, in three steps: Level 1 (from D1 to D5): * Oxycodone placebo : 10 mg PR/day bid (5 mg PR/5 mg PR) * Levodopa placebo 100 mg/day bid (50 mg/50 mg) Level 2 (from D6 to D10): * Oxycodone placebo: 20 mg PR/day tid (10 mg/0 mg/10 mg) * Levodopa placebo: 150 mg/day tid (50 mg/50 mg/50 mg) Level 3 (from D11to D15): * Oxycodone placebo: 40 mg PR/day tid (20 mg/0 mg/20 mg) * Levodopa placebo: 200 mg/day tid (100 mg/50 mg/50 mg) * A fixed dose period: the level 3 dose will be maintained for 8 weeks (from D16 to D71). * A withdrawal period: PR oxycodone Levodopa placebo A titration phase of two weeks, in three steps: Level 1 (from D1 to D5): * Oxycodone : 10 mg PR/day bid (5 mg PR/5 mg PR) * Levodopa placebo 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 placebo: 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 placebo: 200 mg/day tid (100 mg/50 mg/50 mg) * A fixed dose period: the level 3 dose will be maintained for 8 weeks (from D16 to D71). * A withdrawal period: PR oxycodone PR Oxycodone A titration phase of two weeks, in three steps: Level 1 (from D1 to D5): * Oxycodone : 10 mg PR/day bid (5 mg PR/5 mg PR) * Levodopa placebo 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 placebo: 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 placebo: 200 mg/day tid (100 mg/50 mg/50 mg) * A fixed dose period: the level 3 dose will be maintained for 8 weeks (from D16 to D71). * A withdrawal period: Placebo Levodopa placebo A titration phase of two weeks, in three steps: Level 1 (from D1 to D5): * Oxycodone placebo : 10 mg PR/day bid (5 mg PR/5 mg PR) * Levodopa placebo 100 mg/day bid (50 mg/50 mg) Level 2 (from D6 to D10): * Oxycodone placebo: 20 mg PR/day tid (10 mg/0 mg/10 mg) * Levodopa placebo: 150 mg/day tid (50 mg/50 mg/50 mg) Level 3 (from D11to D15): * Oxycodone placebo: 40 mg PR/day tid (20 mg/0 mg/20 mg) * Levodopa placebo: 200 mg/day tid (100 mg/50 mg/50 mg) * A fixed dose period: the level 3 dose will be maintained for 8 weeks (from D16 to D71). * A withdrawal period: levodopa Levodopa A titration phase of two weeks, in three steps: Level 1 (from D1 to D5): * Oxycodone placebo : 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 placebo: 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 placebo: 40 mg PR/day tid (20 mg/0 mg/20 mg) * Levodopa : 200 mg/day tid (100 mg/50 mg/50 mg) * A fixed dose period: the level 3 dose will be maintained for 8 weeks (from D16 to D71). * A withdrawal period:
- Primary Outcome Measures
Name Time Method Average pain intensity 8 weeks Change in average pain rated on visual analog scale (VAS) intensity between baseline and after 8 weeks
- Secondary Outcome Measures
Name Time Method Fatigue : the Parkinson fatigue scale 8 weeks Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)
Functional impact of pain" of the Brief Pain Inventory (BPI) 8 weeks Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)
Maximal pain intensity 8 weeks Change of maximal pain intensity over the preceding week rated on the VAS
Neuropathic Pain Symptoms Inventory (NPSI) 8 weeks Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)
Apathy: the Lille Apathy Rating Scale (LARS) 8 weeks Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)
Depression and anxiety: the Hospital Depression and Anxiety (HAD) scale 8 weeks Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)
Motor assessment and motor fluctuations: MDS UPDRS (MDS Movement Disorder Society - UPDRS Unified Parkinson Disease Rating Scale) 8 weeks Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)
McGill pain questionnaire (SFMPQ) 8 weeks Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)
Sleep : the Pittsburgh sleep quality index 8 weeks Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)
Quality of life: Parkinson's Disease Questionnaire 39 items (PDQ-39) 8 weeks Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)
Acetaminophen consumption reported in diary 8 weeks number of pills or capsules reported in patients diary
Adverse events Day 5, Day 10, Day 15, Day 43, Day 71, Day 79 Adverse events, evaluated with an open-ended questionnaire
changes in Resting-state brain network (3T fMRI) Day 0 /Day 71(Day 71= 8 weeks of treatment) changes in resting-state cerebral networks between Day 0 and Day 71, as assessed by 3T fMRI.
Trial Locations
- Locations (18)
University Hospital of Bordeaux
🇫🇷Bordeaux, France
CHU Amiens
🇫🇷Amiens, France
Henri Mondor Hospital
🇫🇷Créteil, France
University Hospital of Lille
🇫🇷Lille, France
Hospital of Aix-en-Provence
🇫🇷Aix-en-Provence, France
University Hospital of Marseille
🇫🇷Marseille, France
University Hospital of Nancy
🇫🇷Nancy, France
University Hospital of Nantes
🇫🇷Nantes, France
University Hospital of Strasbourg
🇫🇷Strasbourg, France
University Hospital of Nîmes - Caremeau
🇫🇷Nîmes, France
Chu Toulouse
🇫🇷Toulouse, France
University Hospital of Clermont-Ferrand
🇫🇷Clermont-Ferrand, France
Hospital Pierre Wertheimer
🇫🇷Lyon, France
University Hospital of Limoges
🇫🇷Limoges, France
Pitié-Salpêtrière Hospital
🇫🇷Paris, France
University Hospital of Poitiers
🇫🇷Poitiers, France
University Hospital of Rouen
🇫🇷Rouen, France
University Hospital of Rennes
🇫🇷Rennes, France