Amantadine and L-DOPA-induced Dyskinesia in Early Parkinson's Disease (PREMANDYSK)
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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) |
- 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).
- 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 |
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| Contact: Delphine VERNET | 33-5 61 77 72 16 | vernet.d@chu-toulouse.fr |
| 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 | |
| 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: | April 30, 2013 |
| 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 Movement Disorders Central Nervous System Diseases Nervous System Diseases Neurologic Manifestations Signs and Symptoms Parkinsonian Disorders Basal Ganglia Diseases Brain Diseases Neurodegenerative Diseases Amantadine Levodopa Antiparkinson Agents |
Anti-Dyskinesia Agents Central Nervous System Agents Therapeutic Uses Pharmacologic Actions Antiviral Agents Anti-Infective Agents Dopamine Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents |
ClinicalTrials.gov processed this record on May 16, 2013