Clinical trial NCT02601586: Effects of PR Oxycodone and of Levodopa, vs Placebo, on Central Neuropathic Pain in Parkinson's Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Parkinson Disease
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2015-11-10
Enrollment: 67
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Average pain intensity
timeFrame: 8 weeks
Secondary outcomes:
measure: Maximal pain intensity
timeFrame: 8 weeks
measure: Functional impact of pain" of the Brief Pain Inventory (BPI)
timeFrame: 8 weeks
measure: Neuropathic Pain Symptoms Inventory (NPSI)
timeFrame: 8 weeks
measure: McGill pain questionnaire (SFMPQ)
timeFrame: 8 weeks
measure: Depression and anxiety: the Hospital Depression and Anxiety (HAD) scale
timeFrame: 8 weeks
measure: Apathy: the Lille Apathy Rating Scale (LARS)
timeFrame: 8 weeks
measure: Fatigue : the Parkinson fatigue scale
timeFrame: 8 weeks
measure: Sleep : the Pittsburgh sleep quality index
timeFrame: 8 weeks
measure: Motor assessment and motor fluctuations: MDS UPDRS (MDS Movement Disorder Society - UPDRS Unified Parkinson Disease Rating Scale)
timeFrame: 8 weeks
measure: Quality of life: Parkinson's Disease Questionnaire 39 items (PDQ-39)
timeFrame: 8 weeks
measure: Acetaminophen consumption reported in diary
timeFrame: 8 weeks
measure: Adverse events
timeFrame: Day 5, Day 10, Day 15, Day 43, Day 71, Day 79
measure: changes in Resting-state brain network (3T fMRI)
timeFrame: Day 0 /Day 71(Day 71= 8 weeks of treatment)
Other outcomes:
Locations:
city: Aix-en-Provence
country: France
facility: Hospital of Aix-en-Provence
city: Amiens
country: France
facility: CHU Amiens
city: Bordeaux
country: France
facility: University Hospital of Bordeaux
city: Clermont-Ferrand
country: France
facility: University Hospital of Clermont-Ferrand
city: Créteil
country: France
facility: Henri Mondor Hospital
city: Lille
country: France
facility: University Hospital of Lille
city: Limoges
country: France
facility: University Hospital of Limoges
city: Lyon
country: France
facility: Hospital Pierre Wertheimer
city: Marseille
country: France
facility: University Hospital of Marseille
city: Nancy
country: France
facility: University Hospital of Nancy
city: Nantes
country: France
facility: University Hospital of Nantes
city: Nîmes
country: France
facility: University Hospital of Nîmes - Caremeau
city: Paris
country: France
facility: Pitié-Salpêtrière Hospital
city: Poitiers
country: France
facility: University Hospital of Poitiers
city: Rennes
country: France
facility: University Hospital of Rennes
city: Rouen
country: France
facility: University Hospital of Rouen
city: Strasbourg
country: France
facility: University Hospital of Strasbourg
city: Toulouse
country: France
facility: Chu Toulouse
Study officials:
affiliation: CHU Toulouse
name: Christine BREFEL-COURBON, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Toulouse
name: Claire THALAMAS, MD
role: STUDY_CHAIR
References:
citation: Lawn T, Rukavina K, Malcangio M, Howard M, Chaudhuri KR. Response to Mylius et al. Pain. 2022 Mar 1;163(3):e496-e497. doi: 10.1097/j.pain.0000000000002445. No abstract available.