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

Parkinson Disease Clinical Trial

— OXYDOPA  

Official title:

Evaluation of the Analgesic Effects of Prolonged-release Oxycodone and of Levodopa, Versus Placebo, on Central Neuropathic Pain in Parkinson's Disease: OXYDOPA Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02601586
• Other study ID #: 14 7440 01
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: September 2016
• Est. completion date: November 2020

Study information

• Verified date: February 2022
• Source: University Hospital, Toulouse
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: November 2020
• Est. primary completion date: November 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Neuralgia
• Parkinson Disease

Intervention

Drug:
• PR Oxycodone
PR Oxycodone
• Levodopa
Levodopa
• Oxycodone Placebo
Placebo of PR Oxycodone
• Levodopa placebo

Locations

Country	Name	City	State
France	Hospital of Aix-en-Provence	Aix-en-Provence
France	CHU Amiens	Amiens
France	University Hospital of Bordeaux	Bordeaux
France	University Hospital of Clermont-Ferrand	Clermont-Ferrand
France	Henri Mondor Hospital	Créteil
France	University Hospital of Lille	Lille
France	University Hospital of Limoges	Limoges
France	Hospital Pierre Wertheimer	Lyon
France	University Hospital of Marseille	Marseille
France	University Hospital of Nancy	Nancy
France	University Hospital of Nantes	Nantes
France	University Hospital of Nîmes - Caremeau	Nîmes
France	Pitié-Salpêtrière Hospital	Paris
France	University Hospital of Poitiers	Poitiers
France	University Hospital of Rennes	Rennes
France	University Hospital of Rouen	Rouen
France	University Hospital of Strasbourg	Strasbourg
France	Chu Toulouse	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Toulouse

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Average pain intensity	Change in average pain rated on visual analog scale (VAS) intensity between baseline and after 8 weeks	8 weeks
Secondary	Maximal pain intensity	Change of maximal pain intensity over the preceding week rated on the VAS	8 weeks
Secondary	Functional impact of pain" of the Brief Pain Inventory (BPI)	Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)	8 weeks
Secondary	Neuropathic Pain Symptoms Inventory (NPSI)	Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)	8 weeks
Secondary	McGill pain questionnaire (SFMPQ)	Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)	8 weeks
Secondary	Depression and anxiety: the Hospital Depression and Anxiety (HAD) scale	Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)	8 weeks
Secondary	Apathy: the Lille Apathy Rating Scale (LARS)	Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)	8 weeks
Secondary	Fatigue : the Parkinson fatigue scale	Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)	8 weeks
Secondary	Sleep : the Pittsburgh sleep quality index	Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)	8 weeks
Secondary	Motor assessment and motor fluctuations: MDS UPDRS (MDS Movement Disorder Society - UPDRS Unified Parkinson Disease Rating Scale)	Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)	8 weeks
Secondary	Quality of life: Parkinson's Disease Questionnaire 39 items (PDQ-39)	Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)	8 weeks
Secondary	Acetaminophen consumption reported in diary	number of pills or capsules reported in patients diary	8 weeks
Secondary	Adverse events	Adverse events, evaluated with an open-ended questionnaire	Day 5, Day 10, Day 15, Day 43, Day 71, Day 79
Secondary	changes in Resting-state brain network (3T fMRI)	changes in resting-state cerebral networks between Day 0 and Day 71, as assessed by 3T fMRI.	Day 0 /Day 71(Day 71= 8 weeks of treatment)