Long-Term Effects of Amantadine in Parkinsonian (AMANDYSK)

Sponsor

University Hospital, Toulouse (Other)

Overall Status

Completed

CT.gov ID

NCT00632762

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease	Drug: mantadix	Phase 4

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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Evaluation of the Long-term Effects of Amantadine in Parkinsonian's Suffering From Dyskinesia Induced by Levodopa: Study Randomised Double-blind, Placebo - Cessation of a Chronic Prescription. STUDY AMANDYSK.

Study Start Date :

Nov 1, 2007

Actual Primary Completion Date :

Jan 1, 2011

Actual Study Completion Date :

Jan 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Amantadine MANTADIX	Drug: mantadix dose greater or equal to 200 mg/day and progressively increasing doses (100mg every 3 days until the pre-study dose is reached).
Placebo Comparator: 2 placebo	Drug: mantadix dose greater or equal to 200 mg/day and progressively increasing doses (100mg every 3 days until the pre-study dose is reached).

Arm

Intervention/Treatment

Active Comparator: 1

Amantadine MANTADIX

Drug: mantadix

dose greater or equal to 200 mg/day and progressively increasing doses (100mg every 3 days until the pre-study dose is reached).

Placebo Comparator: 2

placebo

Drug: mantadix

dose greater or equal to 200 mg/day and progressively increasing doses (100mg every 3 days until the pre-study dose is reached).

Outcome Measures

Primary Outcome Measures

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 scale [3 months]

Secondary Outcome Measures

The number of patient "responders" [3 months]
The number of premature withdrawals from the trial for reason of an aggravation of dyskinesias [3 months]
The AIMS scale [3 months]
The Clinical Global Impression Severity Scale [3 months]
Other "exploratory" secondary efficacy [3 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hôpital d'Aix en Provence	Aix en Provence	France	13616
2	CHU de Clermont-Ferrand	Clermont-Ferrand	France	63003
3	CHU Timone	Marseille	France	13385
4	Hôpital Haut-Lévêque	Nantes	France	44095
5	CHU Pitié-Salpêtrière	Paris	France	75013