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

March 31, 2026 updated by: University Hospital, Toulouse

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

210

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Aix-en-Provence, France, 13616
        • CHG Aix en Provence
      • Bordeaux, France, 33604
        • CHU de Bordeaux
      • Cahors, France, 46005
        • CH Jean Rougier
      • Clermont-Ferrand, France, 63003
        • Chu Clermont-Ferrand
      • Dijon, France, 21079
        • CHU Dijon
      • Lille, France, 59037
        • CHU Lille
      • Limoges, France, 87042
        • Chu Dupuytren
      • Lyon, France, 69003
        • Hopital Lyon
      • Marseille, France, 13385
        • Hopital de la Timone
      • Montauban, France, 82013
        • CH Montauban
      • Montpellier, France, 34295
        • Hopital Saint Eloi
      • Nantes, France, 44093
        • CHU de Nantes
      • Narbonne, France, 11108
        • CH de Narbonne
      • Paris, France, 75013
        • Hopital Pitie Salpetriere
      • Poitiers, France, 86021
        • Hopital Jean Bernard
      • Rouen, France, 76031
        • CH Charles Nicolle
      • Strasbourg, France
        • CHU de Strasbourg
      • Toulouse, France, 31000
        • CHU de Toulouse

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

31 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Amantadine
Patients with amantadine
Drug: Amantadine
200mg / day once daily in the morning and at noon - oral administration -
Other Names:
  • active drug
Placebo Comparator: Placebo
Patients with amantadine placebo
Drug: placebo
200mg / day once daily in the morning and at noon - oral administration -
Other Names:
  • placebo of amantadine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
after 18 months of Phase 1 of the study
Time Frame: 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).
after 18 months of follow-up

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
abnormal involuntary dyskinetic movements at the end of phase 3 of the study (wash out)
Time Frame: 22 months after inclusion
Rate of patients with abnormal involuntary dyskinetic movements at the end of phase 3 of the study (wash out)
22 months after inclusion
motor fluctuations after 18 months of Phase 1 of the study
Time Frame: 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)
18 months after inclusion
Time to onset of dyskinesias
Time Frame: 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 "
each visits

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Toulouse

Investigators

  • Principal Investigator: Olivier Rascol, MD, University Hospital, Toulouse

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 4, 2012

Primary Completion (Actual)

February 20, 2018

Study Completion (Actual)

February 26, 2019

Study Registration Dates

First Submitted

February 20, 2012

First Submitted That Met QC Criteria

February 20, 2012

First Posted (Estimated)

February 24, 2012

Study Record Updates

Last Update Posted (Actual)

April 6, 2026

Last Update Submitted That Met QC Criteria

March 31, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 11 253 01
  • 2011-005201-75 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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