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Long-Term Effects of Amantadine in Parkinsonian (AMANDYSK)

Phase 4
Completed
Conditions
Parkinson's Disease
Interventions
Drug: mantadix
Registration Number
NCT00632762
Lead Sponsor
University Hospital, Toulouse
Brief Summary

This is a French national trial, conducted using a double-blind, placebo-controlled, randomised design involving 7 centers and 80 patients of both sexes.

The primary objective of the trial is to evaluate the effects of the interruption of a long term treatment (ex. Greater than 6 months) with Amantadine (prescribed as an antidyskinetic) in patients suffering from Parkinson disease being treated with Levodopa and suffering from mid dose dyskinesias.

Secondary objectives of the trial are the evaluation of the other effects of withdrawal of Amantadine on the same group of patients: motor fluctuations, vigilance, apathy, fatigue, certain cognitive aspects, the disappearance or development of undesirable side effects and quality of life.

Detailed Description

The trial will involve the participation of the patients for a period of 3 months each. The two groups of patients to be studied are:

* a group who will continue their treatment with Amantadine with no modification to dosage;

* a group who will have their dosage of Amantadine progressively replaced over several days with a placebo (with the aim of avoiding a "brutal" withdrawal which has been associated with symptoms of hyperthermia in rare cases in the literature).

The trial visits are scheduled as such:

* weekly visits for the first 4 weeks, with a telephone call between each visit to assure that the withdrawal from Amantadine causes any problems.

* every 2 weeks from week 4 until week 8, with weekly telephone calls in between these visits.

* a telephone call in the 10th week followed by an end of study visit in week 12. In the event of an early withdrawal from the trial, and assuming that the patient gives their consent, a complete end of study visit will be performed prior to recommencing open label treatment with Amantadine in progressively increasing doses (100mg every 3 days until the pre-study dose is reached).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
80
Inclusion Criteria
  • Female or Male Patients with Idiopathic Parkinson's disease
  • Presenting peak dose dyskinesias under levodopa therapy
  • Patient receiving Amantadine for dyskinesia at a dose greater or equal to 200 mg/day (minimum dose at which one can observe anti dyskinetic effects) for at least 6 months.
  • Patients between 30 and 80 years of age
  • Patients having reported a subjective amelioration in their dyskinesias under Amantadine (at the beginning of their treatment with same)
  • Patient with a Mini- Mental State Exam score > 24
  • Patient not presenting a cognitive problem that could impair the comprehension of the patient and their participation in the protocol (patient diaries)
  • Receiving an anti-parkinsonian treatment at a stable dose for at least 2 months with the expectation that the treatment will remain unchanged throughout the course of the patients participation in the trial.
  • Signed informed consent obtained
  • Patient eligible for social security (specific requirement under french law)
Exclusion Criteria
  • Atypical parkinsonian syndrome (progressive supranuclear palsy, multi-system atrophy, etc)

    • Patient with parkinsonian syndrome secondary to medication
    • Patients presenting with dyskinesias whose severity allow an insufficient margin for observing any aggravation which follows a potential withdrawal of treatment (UPDRS 32+33 >6)
    • Patients receiving treatment with Apokinon© injector pens (unless that treatment enters into a therapeutic schema at fixed hours)
    • Patient presenting with dementia or an evolving dopaminergic psychosis
    • Patient receiving neuroleptics or anticholinesterases
    • Patients having received functional surgery for their Parkinsons' Disease
    • Patients pregnant or at risk of same
    • Patients who are: wards of the state requirement under french law).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1mantadixAmantadine MANTADIX
2mantadixplacebo
Primary Outcome Measures
NameTimeMethod
The primary efficacy endpoint is the variation in the sum of the items 32 and 33 (duration and severity of dyskinesias - maximum score = 8) evaluated using Part IV of the UPDRS scale3 months
Secondary Outcome Measures
NameTimeMethod
The number of patient "responders"3 months
The number of premature withdrawals from the trial for reason of an aggravation of dyskinesias3 months
The AIMS scale3 months
The Clinical Global Impression Severity Scale3 months
Other "exploratory" secondary efficacy3 months

Trial Locations

Locations (5)

Hôpital Haut-Lévêque

🇫🇷

Nantes, France

Hôpital d'Aix en Provence

🇫🇷

Aix en Provence, France

CHU de Clermont-Ferrand

🇫🇷

Clermont-Ferrand, France

CHU Timone

🇫🇷

Marseille, France

CHU Pitié-Salpêtrière

🇫🇷

Paris, France

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