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

Sponsor

University Hospital, Toulouse (Other)

Overall Status

Completed

CT.gov ID

NCT01538329

Collaborator

(none)

210

Enrollment

Locations

Arms

83.8

Actual Duration (Months)

11.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease	Drug: Amantadine Drug: placebo	Phase 2

Detailed Description

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 Design

Study Type:

Interventional

Actual Enrollment :

210 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, 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)

Actual Study Start Date :

Mar 4, 2012

Actual Primary Completion Date :

Feb 20, 2018

Actual Study Completion Date :

Feb 26, 2019

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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)
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 "

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CHG Aix en Provence	Aix en Provence	France	13616
2	CHU de Bordeaux	Bordeaux	France	33604
3	CH Jean Rougier	Cahors	France	46005
4	CHU Clermont-Ferrand	Clermont-Ferrand	France	63003
5	CHU Dijon	Dijon	France	21079
6	CHU Lille	Lille	France	59037
7	CHU Dupuytren	Limoges	France	87042
8	Hopital Lyon	Lyon	France	69003
9	Hopital de la Timone	Marseille	France	13385
10	CH Montauban	Montauban	France	82013
11	hopital Saint Eloi	Montpellier	France	34295
12	CHu de Nantes	Nantes	France	44093
13	CH de Narbonne	Narbonne	France	11108
14	Hopital pitié Salpétriére	Paris	France	75013
15	Hopital Jean Bernard	Poitiers	France	86021
16	CH Charles Nicolle	Rouen	France	76031
17	CHU de Strasbourg	Strasbourg	France
18	CHU de Toulouse	Toulouse	France	31000