search
Back to results

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

Primary Purpose

Parkinson Disease

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Amantadine
placebo
Sponsored by
University Hospital, Toulouse
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Parkinson Disease focused on measuring Dyskinesia, L-DOPA, Early introduced treatment, Amantadine

Eligibility Criteria

35 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • CHG Aix en Provence
  • CHU de Bordeaux
  • CH Jean Rougier
  • CHU Clermont-Ferrand
  • CHU Dijon
  • CHU Lille
  • CHU Dupuytren
  • Hopital Lyon
  • Hopital de la Timone
  • CH Montauban
  • hopital Saint Eloi
  • CHu de Nantes
  • CH de Narbonne
  • Hopital pitié Salpétriére
  • Hopital Jean Bernard
  • CH Charles Nicolle
  • CHU de Strasbourg
  • CHU de Toulouse

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Amantadine

Placebo

Arm Description

Patients with amantadine

Patients with amantadine placebo

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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)
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)
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 "

Full Information

First Posted
February 20, 2012
Last Updated
February 2, 2021
Sponsor
University Hospital, Toulouse
search

1. Study Identification

Unique Protocol Identification Number
NCT01538329
Brief Title
Amantadine and L-DOPA-induced Dyskinesia in Early Parkinson's Disease
Acronym
PREMANDYSK
Official Title
Impact of Amantadine on L-DOPA-induced Dyskinesia in Early Parkinson's Disease: a Placebo-controlled Randomized Study (the PREMANDYSK Study)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
March 4, 2012 (Actual)
Primary Completion Date
February 20, 2018 (Actual)
Study Completion Date
February 26, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Toulouse

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease
Keywords
Dyskinesia, L-DOPA, Early introduced treatment, Amantadine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
210 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Amantadine
Arm Type
Experimental
Arm Description
Patients with amantadine
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patients with amantadine placebo
Intervention Type
Drug
Intervention Name(s)
Amantadine
Other Intervention Name(s)
active drug
Intervention Description
200mg / day once daily in the morning and at noon - oral administration -
Intervention Type
Drug
Intervention Name(s)
placebo
Other Intervention Name(s)
placebo of amantadine
Intervention Description
200mg / day once daily in the morning and at noon - oral administration -
Primary Outcome Measure Information:
Title
after 18 months of Phase 1 of the study
Description
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).
Time Frame
after 18 months of follow-up
Secondary Outcome Measure Information:
Title
abnormal involuntary dyskinetic movements at the end of phase 3 of the study (wash out)
Description
Rate of patients with abnormal involuntary dyskinetic movements at the end of phase 3 of the study (wash out)
Time Frame
22 months after inclusion
Title
motor fluctuations after 18 months of Phase 1 of the study
Description
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 Frame
18 months after inclusion
Title
Time to onset of dyskinesias
Description
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 "
Time Frame
each visits

10. Eligibility

Sex
All
Minimum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olivier Rascol, MD
Organizational Affiliation
University Hospital, Toulouse
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHG Aix en Provence
City
Aix en Provence
ZIP/Postal Code
13616
Country
France
Facility Name
CHU de Bordeaux
City
Bordeaux
ZIP/Postal Code
33604
Country
France
Facility Name
CH Jean Rougier
City
Cahors
ZIP/Postal Code
46005
Country
France
Facility Name
CHU Clermont-Ferrand
City
Clermont-Ferrand
ZIP/Postal Code
63003
Country
France
Facility Name
CHU Dijon
City
Dijon
ZIP/Postal Code
21079
Country
France
Facility Name
CHU Lille
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
CHU Dupuytren
City
Limoges
ZIP/Postal Code
87042
Country
France
Facility Name
Hopital Lyon
City
Lyon
ZIP/Postal Code
69003
Country
France
Facility Name
Hopital de la Timone
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
CH Montauban
City
Montauban
ZIP/Postal Code
82013
Country
France
Facility Name
hopital Saint Eloi
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
CHu de Nantes
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
CH de Narbonne
City
Narbonne
ZIP/Postal Code
11108
Country
France
Facility Name
Hopital pitié Salpétriére
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Hopital Jean Bernard
City
Poitiers
ZIP/Postal Code
86021
Country
France
Facility Name
CH Charles Nicolle
City
Rouen
ZIP/Postal Code
76031
Country
France
Facility Name
CHU de Strasbourg
City
Strasbourg
Country
France
Facility Name
CHU de Toulouse
City
Toulouse
ZIP/Postal Code
31000
Country
France

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs