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

NCT ID: NCT02601586

Last Updated: 2022-03-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

67 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-09-30

Study Completion Date

2020-11-30

Brief Summary

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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

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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.

Conditions

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Parkinson Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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:

Group Type EXPERIMENTAL

PR Oxycodone

Intervention Type DRUG

PR Oxycodone

Levodopa placebo

Intervention Type 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:

Group Type ACTIVE_COMPARATOR

Levodopa

Intervention Type DRUG

Levodopa

Oxycodone Placebo

Intervention Type DRUG

Placebo of PR 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:

Group Type PLACEBO_COMPARATOR

Oxycodone Placebo

Intervention Type DRUG

Placebo of PR Oxycodone

Levodopa placebo

Intervention Type DRUG

Interventions

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PR Oxycodone

PR Oxycodone

Intervention Type DRUG

Levodopa

Levodopa

Intervention Type DRUG

Oxycodone Placebo

Placebo of PR Oxycodone

Intervention Type DRUG

Levodopa placebo

Intervention Type DRUG

Other Intervention Names

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PR Oxycontin Modopar

Eligibility Criteria

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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


* Patients with claustrophobia
* Patients with a hearing aid, cardiac prosthesis, pacemaker, surgical clip
* Patients refusing to be informed of abnormalities are detected on MRI
Minimum Eligible Age

40 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Toulouse

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christine BREFEL-COURBON, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Claire THALAMAS, MD

Role: STUDY_CHAIR

University Hospital, Toulouse

Locations

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Hospital of Aix-en-Provence

Aix-en-Provence, , France

Site Status

CHU Amiens

Amiens, , France

Site Status

University Hospital of Bordeaux

Bordeaux, , France

Site Status

University Hospital of Clermont-Ferrand

Clermont-Ferrand, , France

Site Status

Henri Mondor Hospital

Créteil, , France

Site Status

University Hospital of Lille

Lille, , France

Site Status

University Hospital of Limoges

Limoges, , France

Site Status

Hospital Pierre Wertheimer

Lyon, , France

Site Status

University Hospital of Marseille

Marseille, , France

Site Status

University Hospital of Nancy

Nancy, , France

Site Status

University Hospital of Nantes

Nantes, , France

Site Status

University Hospital of Nîmes - Caremeau

Nîmes, , France

Site Status

Pitié-Salpêtrière Hospital

Paris, , France

Site Status

University Hospital of Poitiers

Poitiers, , France

Site Status

University Hospital of Rennes

Rennes, , France

Site Status

University Hospital of Rouen

Rouen, , France

Site Status

University Hospital of Strasbourg

Strasbourg, , France

Site Status

Chu Toulouse

Toulouse, , France

Site Status

Countries

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France

References

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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.

Reference Type DERIVED
PMID: 35148289 (View on PubMed)

Other Identifiers

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14 7440 01

Identifier Type: -

Identifier Source: org_study_id

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