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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University Hospital, Toulouse
Sponsor:
Information provided by (Responsible Party):
University Hospital, Toulouse
ClinicalTrials.gov Identifier:
NCT01538329
First received: February 20, 2012
Last updated: July 25, 2014
Last verified: July 2014
  Purpose

Traditionally amantadine is used at the beginning of 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 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.


Condition Intervention Phase
Early Parkinson Disease
Drug: Amantadine
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Impact of Amantadine on L-DOPA-induced Dyskinesia in Early Parkinson's Disease: a Placebo-controlled Randomized Study (the PREMANDYSK Study)

Resource links provided by NLM:


Further study details as provided by University Hospital, Toulouse:

Primary Outcome Measures:
  • after 18 months of Phase 1 of the study [ Time Frame: after 18 months of follow-up ] [ Designated as safety issue: No ]
    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:
  • abnormal involuntary dyskinetic movements at the end of phase 3 of the study (wash out) [ Time Frame: 22 months after inclusion ] [ Designated as safety issue: No ]
    Rate of patients with abnormal involuntary dyskinetic movements at the end of phase 3 of the study (wash out)

  • motor fluctuations after 18 months of Phase 1 of the study [ Time Frame: 18 months after inclusion ] [ Designated as safety issue: No ]
    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 [ Time Frame: each visits ] [ Designated as safety issue: No ]
    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 "


Estimated Enrollment: 202
Study Start Date: March 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Amantadine Drug: Amantadine
200mg / day once daily in the morning and at noon - oral administration -
Placebo Comparator: Placebo Drug: placebo
200mg / day once daily in the morning and at noon - oral administration -

  Eligibility

Ages Eligible for Study:   35 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or Female 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 MAO-B or a 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, MMS <26,
  • Patient with behavioral disorder, ECMP item ≥ 3
  • Female subjects of childbearing potential without effective contraception
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01538329

Contacts
Contact: Delphine VERNET 33-5 61 77 72 16 vernet.d@chu-toulouse.fr

Locations
France
CHG Aix en Provence Recruiting
Aix en Provence, France, 13616
Principal Investigator: François Viallet, MD         
CHU de Bordeaux Recruiting
Bordeaux, France, 33604
Principal Investigator: François Tison, MD         
CH Jean Rougier Recruiting
Cahors, France, 46005
Principal Investigator: Jean-Marc Boulesteix, MD         
CHU Clermont-Ferrand Recruiting
Clermont-Ferrand, France, 63003
Principal Investigator: franck Durif, MD         
CHU Dijon Recruiting
Dijon, France, 21079
Principal Investigator: Maurice Giroud, MD         
CHU Lille Recruiting
Lille, France, 59037
Principal Investigator: Alain Destée, MD         
CHU Dupuytren Recruiting
Limoges, France, 87042
Principal Investigator: Frederic Torny, MD         
Hopital Lyon Recruiting
Lyon, France, 69003
Principal Investigator: Emmanuel Broussolle, MD         
Hopital de la Timone Recruiting
Marseille, France, 13385
Principal Investigator: Jean-Philippe Azulay, MD         
CH Montauban Recruiting
Montauban, France, 82013
Principal Investigator: Nicolas Boulloche, MD         
hopital Saint Eloi Recruiting
Montpellier, France, 34295
Principal Investigator: Christian Geny, MD         
CHu de Nantes Recruiting
Nantes, France, 44093
Principal Investigator: Philippe Damier, MD         
CH de Narbonne Recruiting
Narbonne, France, 11108
Principal Investigator: Jany Rey Zermati, MD         
Hopital pitié Salpétriére Recruiting
Paris, France, 75013
Contact: Jean-Christophe Corvol, MD    0142165773    jean-christophe.corvol@psl.aphp.fr   
Principal Investigator: Jean-Christophe Corvol, MD         
Hopital Jean Bernard Recruiting
Poitiers, France, 86021
Principal Investigator: Jean-Luc Houeto, MD         
CH Charles Nicolle Recruiting
Rouen, France, 76031
Principal Investigator: David Maltête, MD         
CHU de Strasbourg Recruiting
Strasbourg, France
Principal Investigator: Christine Tanchant, MD         
CHU de Toulouse Recruiting
Toulouse, France, 31000
Principal Investigator: Olivier Rascol, MD         
Sponsors and Collaborators
University Hospital, Toulouse
Investigators
Principal Investigator: Olivier Rascol, MD University Hospital, Toulouse
  More Information

No publications provided

Responsible Party: University Hospital, Toulouse
ClinicalTrials.gov Identifier: NCT01538329     History of Changes
Other Study ID Numbers: 11 253 01
Study First Received: February 20, 2012
Last Updated: July 25, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Toulouse:
Dyskinesia
L-DOPA
Early introduced treatment
Amantadine

Additional relevant MeSH terms:
Dyskinesias
Parkinson Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Neurologic Manifestations
Parkinsonian Disorders
Signs and Symptoms
Amantadine
Analgesics
Analgesics, Non-Narcotic
Anti-Dyskinesia Agents
Anti-Infective Agents
Antiparkinson Agents
Antiviral Agents
Central Nervous System Agents
Dopamine Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014