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

NCT01538329 | Completed Phase 2

• 1 other identifier: 11 253 01
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 18

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.

Conditions

Parkinson Disease

Keywords

Dyskinesia; L-DOPA; Early introduced treatment; Amantadine

Outcome Measures

Primary Outcomes (1)

• 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).

  after 18 months of follow-up

Secondary Outcomes (3)

• 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

  18 months after inclusion

• Time to onset of dyskinesias

  each visits

Study Arms (2)

Amantadine

EXPERIMENTAL

Patients with amantadine

Drug: Amantadine

Placebo

PLACEBO COMPARATOR

Patients with amantadine placebo

Drug: placebo

Interventions

Amantadine DRUG

200mg / day once daily in the morning and at noon - oral administration -

Also known as: active drug

Amantadine

placebo DRUG

200mg / day once daily in the morning and at noon - oral administration -

Also known as: placebo of amantadine

Placebo

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (18)

CHG Aix en Provence

Aix-en-Provence, 13616, France

Location

CHU de Bordeaux

Bordeaux, 33604, France

Location

CH Jean Rougier

Cahors, 46005, France

Location

CHU Clermont-Ferrand

Clermont-Ferrand, 63003, France

Location

CHU Dijon

Dijon, 21079, France

Location

CHU Lille

Lille, 59037, France

Location

CHU Dupuytren

Limoges, 87042, France

Location

Hopital Lyon

Lyon, 69003, France

Location

Hopital de la Timone

Marseille, 13385, France

Location

CH Montauban

Montauban, 82013, France

Location

hopital Saint Eloi

Montpellier, 34295, France

Location

CHu de Nantes

Nantes, 44093, France

Location

CH de Narbonne

Narbonne, 11108, France

Location

Hopital pitié Salpétriére

Paris, 75013, France

Location

Hopital Jean Bernard

Poitiers, 86021, France

Location

CH Charles Nicolle

Rouen, 76031, France

Location

CHU de Strasbourg

Strasbourg, France

Location

CHU de Toulouse

Toulouse, 31000, France

Location

MeSH Terms

Conditions

Parkinson Disease; Dyskinesias

Interventions

Amantadine; Bulk Drugs

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Pharmaceutical Preparations

Study Officials

• Olivier Rascol, MD

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2012
• First Posted: February 24, 2012
• Study Start: March 4, 2012
• Primary Completion: February 20, 2018
• Study Completion: February 26, 2019
• Last Updated: February 5, 2021

Record last verified: 2021-02

Locations

FR (18)