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

Parkinson Disease Clinical Trial

— PREMANDYSK  

Official title:

Impact of Amantadine on L-DOPA-induced Dyskinesia in Early Parkinson's Disease: a Placebo-controlled Randomized Study (the PREMANDYSK Study)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01538329
• Other study ID #: 11 253 01
• Status: Completed
• Phase: Phase 2
• Start date: March 4, 2012
• Est. completion date: February 26, 2019

Study information

• Verified date: February 2021
• Source: University Hospital, Toulouse
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 210
• Est. completion date: February 26, 2019
• Est. primary completion date: February 20, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Dyskinesias
• Parkinson Disease

Intervention

Drug:
• Amantadine
200mg / day once daily in the morning and at noon - oral administration -
• placebo
200mg / day once daily in the morning and at noon - oral administration -

Locations

Country	Name	City	State
France	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

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Toulouse

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	after 18 months of Phase 1 of the study	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).	after 18 months of follow-up
Secondary	abnormal involuntary dyskinetic movements at the end of phase 3 of the study (wash out)	Rate of patients with abnormal involuntary dyskinetic movements at the end of phase 3 of the study (wash out)	22 months after inclusion
Secondary	motor fluctuations after 18 months of Phase 1 of the study	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)	18 months after inclusion
Secondary	Time to onset of dyskinesias	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 "	each visits