Amantadine and L-DOPA-induced Dyskinesia in Early Parkinson's Disease
- Registration Number
- NCT01538329
- Lead Sponsor
- University Hospital, Toulouse
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 210
- 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).
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Amantadine Amantadine Patients with amantadine Placebo placebo Patients with amantadine placebo
- Primary Outcome Measures
Name Time Method after 18 months of Phase 1 of the study after 18 months of follow-up Rate of patient with abnormal involuntary dyskinetic movements (as specifically defined in the protocol) after 18 months of Phase 1 of the study (amantadine versus placebo).
- Secondary Outcome Measures
Name Time Method motor fluctuations after 18 months of Phase 1 of the study 18 months after inclusion Rate of patients with non-motor fluctuations after 18 months of Phase 1 (defined by the specific scale developed by the Marseille team involved in the project)
Time to onset of dyskinesias each visits Time to onset of dyskinesias defined as the study visit at which the investigator answers "yes" for the first time the question "do you think this patient has dyskinesia as defined in Protocol "
abnormal involuntary dyskinetic movements at the end of phase 3 of the study (wash out) 22 months after inclusion Rate of patients with abnormal involuntary dyskinetic movements at the end of phase 3 of the study (wash out)
Trial Locations
- Locations (18)
CHU de Strasbourg
🇫🇷Strasbourg, France
CH Jean Rougier
🇫🇷Cahors, France
CHU Dupuytren
🇫🇷Limoges, France
CHU de Bordeaux
🇫🇷Bordeaux, France
CHu de Nantes
🇫🇷Nantes, France
Hopital de la Timone
🇫🇷Marseille, France
hopital Saint Eloi
🇫🇷Montpellier, France
Hopital pitié Salpétriére
🇫🇷Paris, France
Hopital Jean Bernard
🇫🇷Poitiers, France
CH Charles Nicolle
🇫🇷Rouen, France
CH Montauban
🇫🇷Montauban, France
CH de Narbonne
🇫🇷Narbonne, France
CHU de Toulouse
🇫🇷Toulouse, France
CHG Aix en Provence
🇫🇷Aix en Provence, France
Hopital Lyon
🇫🇷Lyon, France
CHU Clermont-Ferrand
🇫🇷Clermont-Ferrand, France
CHU Lille
🇫🇷Lille, France
CHU Dijon
🇫🇷Dijon, France