Evaluation of the Analgesic Effects of Prolonged-release Oxycodone and of Levodopa, Versus Placebo, on Central Neuropathic Pain in Parkinson's Disease: OXYDOPA Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 32
- 主要终点
- Average pain intensity
研究概览
简要总结
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
详细描述
The treatment period (11 weeks) will be divided into three periods:
- 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)
- 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.
- A withdrawal period: The dose of the study treatment will gradually be reduced, over an eight-day period:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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:
干预措施: Levodopa placebo (Drug)
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:
干预措施: PR Oxycodone (Drug)
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:
干预措施: Oxycodone Placebo (Drug)
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:
干预措施: Oxycodone Placebo (Drug)
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:
干预措施: Levodopa placebo (Drug)
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:
干预措施: Levodopa (Drug)
结局指标
主要结局
Average pain intensity
时间窗: 8 weeks
Change in average pain rated on visual analog scale (VAS) intensity between baseline and after 8 weeks
次要结局
- Fatigue : the Parkinson fatigue scale(8 weeks)
- Functional impact of pain" of the Brief Pain Inventory (BPI)(8 weeks)
- Maximal pain intensity(8 weeks)
- Neuropathic Pain Symptoms Inventory (NPSI)(8 weeks)
- Apathy: the Lille Apathy Rating Scale (LARS)(8 weeks)
- Depression and anxiety: the Hospital Depression and Anxiety (HAD) scale(8 weeks)
- Motor assessment and motor fluctuations: MDS UPDRS (MDS Movement Disorder Society - UPDRS Unified Parkinson Disease Rating Scale)(8 weeks)
- McGill pain questionnaire (SFMPQ)(8 weeks)
- Sleep : the Pittsburgh sleep quality index(8 weeks)
- Quality of life: Parkinson's Disease Questionnaire 39 items (PDQ-39)(8 weeks)
- Acetaminophen consumption reported in diary(8 weeks)
- Adverse events(Day 5, Day 10, Day 15, Day 43, Day 71, Day 79)
- changes in Resting-state brain network (3T fMRI)(Day 0 /Day 71(Day 71= 8 weeks of treatment))