Long-Term Effects of Amantadine in Parkinsonian (AMANDYSK) - Full Text View

Sponsored by:	University Hospital, Toulouse
Information provided by:	University Hospital, Toulouse
ClinicalTrials.gov Identifier:	NCT00632762

Purpose

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 antidyskenetic) in patients suffering from Parkinsons 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 disapearance or developpment of undesirable side effects and quality of life.

Condition	Intervention	Phase
Parkinson's Disease	Drug: mantadix	Phase IV

Study Type:

Interventional

Study Design:

Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Official Title:

Evaluation of the Long-term Effects of Amantadine in Parkinsian's Suffering From Dyskinesia Induced by Levodopa:

Study Randomised Double-blind, Placebo - Cessation of a Chronic Prescription. STUDY AMANDYSK.

Resource links provided by NLM:

Genetics Home Reference related topics: familial paroxysmal nonkinesigenic dyskinesia Parkinson disease

MedlinePlus related topics: Parkinson's Disease

Drug Information available for: Amantadine sulfate Amantadine hydrochloride Amantadine

U.S. FDA Resources

Further study details as provided by University Hospital, Toulouse:

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 [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

The number of patient "responders" [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
The number of premature withdrawals from the trial for reason of an aggravation of dyskinesias [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
The AIMS scale [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
The Clinical Global Impression Severity Scale [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
Other "exploratory" secondary efficacy [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	80
Study Start Date:	November 2007
Estimated Study Completion Date:	June 2010
Estimated Primary Completion Date:	January 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator 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).
2: Placebo Comparator 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).

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 hyperthermie 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).

Eligibility

Ages Eligible for Study:	30 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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 evoloving dopaminergic psychosis
- Patient receiving neuroleptics or anticholinesterases
- Patients having received fonctional surgery for their Parkinsons' Disease
- Patients pregnant or at risk of same
- Patients who are: wards of the state or prisoners (requirement under french law)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00632762

Contacts

Contact: Olivier Rascol, MD

05 61 779103

rascol@cict.fr

Locations

France
CHU Timone	Recruiting
Marseille, France, 13385
Contact: Jean-Philippe Azulay, MD 04 91 38 65 79 ext 33 jean-philippe-azulay@ap-hm.fr
Hôpital Haut-Lévêque	Recruiting
Nantes, France, 44095
Contact: Philippe Damier, MD 02 40 16 52 05 philippe.damier@chu-nantes.fr
Hôpital d'Aix en Provence	Recruiting
Aix en Provence, France, 13616
Contact: François Viallet, MD 04 42 33 50 73 viallet@ch-aix.fr
CHU Pitié-Salpêtrière	Recruiting
PARIS, France, 75013
Contact: Dr Lucette Lacomblez, MD 01 40 77 97 00
Contact: Dr Jean-Christophe Corvol, MD 01 40 77 97 00
CHU de Clermont-Ferrand	Recruiting
Clermont-Ferrand, France, 63003
Contact: Pr Franck Durif, MD 04 73 75 07 50 fdurif@chu_clermontferrand.fr

Sponsors and Collaborators

University Hospital, Toulouse

Investigators

Principal Investigator:

Olivier Rascol, MD

CHU Toulouse

More Information

Publications:

Alves G, Wentzel-Larsen T, Larsen JP. Is fatigue an independent and persistent symptom in patients with Parkinson disease? Neurology. 2004 Nov 23;63(10):1908-11.

Bibbiani F, Oh JD, Kielaite A, Collins MA, Smith C, Chase TN. Combined blockade of AMPA and NMDA glutamate receptors reduces levodopa-induced motor complications in animal models of PD. Exp Neurol. 2005 Dec;196(2):422-9. Epub 2005 Oct 3.

Chapuis S, Ouchchane L, Metz O, Gerbaud L, Durif F. Impact of the motor complications of Parkinson's disease on the quality of life. Mov Disord. 2005 Feb;20(2):224-30.

Responsible Party:	UH TOULOUSE ( Marie-Elise LLAU )
Study ID Numbers:	06 008 01
Study First Received:	February 20, 2008
Last Updated:	August 21, 2009
ClinicalTrials.gov Identifier:	NCT00632762 History of Changes
Health Authority:	France: Ministry of Health

Keywords provided by University Hospital, Toulouse:

Amantadine benefit
Dyskinesia
Parkinson's disease

Study placed in the following topic categories:

Anti-Infective Agents
Neurotransmitter Agents
Levodopa
Ganglion Cysts
Basal Ganglia Diseases
Central Nervous System Diseases
Brain Diseases
Neurodegenerative Diseases
Dyskinesias
Antiviral Agents

Dopamine
Analgesics, Non-Narcotic
Parkinson Disease
Movement Disorders
Dopamine Agents
Peripheral Nervous System Agents
Analgesics
Parkinsonian Disorders
Amantadine

Additional relevant MeSH terms:

Anti-Infective Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Dyskinesia Agents
Physiological Effects of Drugs
Basal Ganglia Diseases
Nervous System Diseases
Central Nervous System Diseases
Antiparkinson Agents
Brain Diseases
Neurodegenerative Diseases
Antiviral Agents

Pharmacologic Actions
Sensory System Agents
Analgesics, Non-Narcotic
Parkinson Disease
Movement Disorders
Therapeutic Uses
Dopamine Agents
Peripheral Nervous System Agents
Analgesics
Parkinsonian Disorders
Amantadine
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 10, 2009