Amantadine and L-DOPA-induced Dyskinesia in Early Parkinson's Disease

NCT ID: NCT01538329

Last Updated: 2021-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 210 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-04
• Study Completion Date: 2019-02-26

Brief Summary

Traditionally amantadine is used at the beginning of Parkinson Disease (PD) treatment in the early stages of the disease, as a modest antiparkinsonian symptomatic treatment. This treatment is usually maintained for no more than the first few months of management, before resorting to drugs deemed more effective as dopamine agonists and lévo-DOPA (L-DOPA). A more modern use of the drug is at a more advanced stage of PD when dyskinesia are already established and become disabling for the patients. There is no data between these two extremes of life stages of Parkinsonism. However, the mechanisms of action of amantadine and the pathophysiology of the motor complications induced by L-DOPA, in particular dyskinesia suggest that the early and prolonged use of amantadine in the early years of management, before L-DOPA-induced dyskinesia have already emerged, should have a positive impact on long-term occurrence and fate of these symptoms, possibly through a glutamatergic mechanism of brain plasticity-of the "disease modification" type.

Detailed Description

Traditionally amantadine is used at the beginning of Parkinson Disease (PD) treatment in the early stages of the disease, as a modest antiparkinsonian symptomatic treatment. This treatment is usually maintained for no more than the first few months of management, before resorting to drugs deemed more effective as dopamine agonists and lévo-DOPA (L-DOPA). A more modern use of the drug is at a more advanced stage of PD when dyskinesia are already established and become disabling for the patients. There is no data between these two extremes of life stages of Parkinsonism. However, the mechanisms of action of amantadine and the pathophysiology of the motor complications induced by L-DOPA, in particular dyskinesia suggest that the early and prolonged use of amantadine in the early years of management, before L-DOPA-induced dyskinesia have already emerged, should have a positive impact on long-term occurrence and fate of these symptoms, possibly through a glutamatergic mechanism of brain plasticity-of the "disease modification" type.

The primary purpose of this study is to demonstrate that early introduction of treatment with amantadine (200 mg / d) in the early years of therapeutic care, that is to say during the "honeymoon" of levodopa (early phase of disease <3 years of diagnosis <1 year of L-dopa and lack of complications of levodopa therapy) decreases the rate of subjects with abnormal involuntary dyskinetic movements after 18 months of follow-up.

Conditions

Parkinson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Amantadine

Patients with amantadine

Group Type: EXPERIMENTAL

Amantadine

Intervention Type: DRUG

200mg / day once daily in the morning and at noon - oral administration -

Placebo

Patients with amantadine placebo

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

200mg / day once daily in the morning and at noon - oral administration -

Interventions

Amantadine

200mg / day once daily in the morning and at noon - oral administration -

Intervention Type: DRUG

placebo

200mg / day once daily in the morning and at noon - oral administration -

Intervention Type: DRUG

Other Intervention Names

active drug; placebo of amantadine

Eligibility Criteria

Inclusion Criteria

• Age over 35 years,
• Patients having signed an informed consent before any specific study procedures,
• Patients having a health Insurance Coverage (according to local regulatory requirements),
• Patients suffering from idiopathic Parkinson's disease meeting the definition criteria of the UKPD Brain Bank (Gibb and Lees, 1988),
• Parkinson's disease diagnosed for <3 years,
• Patients receiving treatment with L-DOPA from <1year,
• Lack of complications of levodopa therapy
• Patients receiving a stable antiparkinsonian treatment that may involve, in addition to L-DOPA, a dopamine agonist, a monoamine oxidase-B (MAO-B) or a catecholamine O-methyl transferase (COMT) inhibitor, an anti-cholinergic for at least 2 months before enrollment and in whom we presume it will be possible to maintain this treatment unchanged during the study period (except the dose of L-dopa which can be adjusted during the study after the third month of Phase 1).

Exclusion Criteria

• Atypical parkinsonian syndromes,
• Drug-induced Parkinsonism,
• Juvenile Parkinson,
• Patients with complications of levodopa therapy
• Inability to keep the current stable antiparkinsonian treatment during the study period, apart from L-DOPA,
• Pretreatment with amantadine,
• amantadine counter-indication
• Neuroleptic treatment,
• Patients with dementia, Mini Mental Status (MMS) <26,
• Patient with behavioral disorder, ECMP item ≥ 3
• Female subjects of childbearing potential without effective contraception

• Minimum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Olivier Rascol, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Locations

CHG Aix en Provence

Aix-en-Provence, , France

CHU de Bordeaux

Bordeaux, , France

CH Jean Rougier

Cahors, , France

CHU Clermont-Ferrand

Clermont-Ferrand, , France

CHU Dijon

Dijon, , France

CHU Lille

Lille, , France

CHU Dupuytren

Limoges, , France

Hopital Lyon

Lyon, , France

Hopital de la Timone

Marseille, , France

CH Montauban

Montauban, , France

hopital Saint Eloi

Montpellier, , France

CHu de Nantes

Nantes, , France

CH de Narbonne

Narbonne, , France

Hopital pitié Salpétriére

Paris, , France

Hopital Jean Bernard

Poitiers, , France

CH Charles Nicolle

Rouen, , France

CHU de Strasbourg

Strasbourg, , France

CHU de Toulouse

Toulouse, , France

Countries

France

Other Identifiers

11 253 01

Identifier Type: -

Identifier Source: org_study_id