- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00767091
Study of Rivastigmine to Treat Parkinsonian Apathy Without Dementia (CHoPA-I)
A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicentric Trial
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Overall study duration: 2 years. Planned inclusion period: 12 months. Study duration for individual patients: 7 months (2 weeks between screening and randomization, 6 months of double-blind treatment and then a 2-week wash-out period).
Primary objective (V1 and V6):
To assess efficacy of anticholinesterasic treatment (trans-dermal patch of rivastigmine , Exelon®) on parkinsonian apathy assessed by the Lille Apathy Rating Scale in patients with advanced Parkinson's disease without dementia or depression
Additional Efficacy Endpoints (V1 and V6):
- the NeuroPsychiatric Inventory, the apathy/retardation subscore of the MADRS (tri-dimensional analysis, the Activity of Daily Living scale, the simple and complex reaction times (selective attention), the quality of life (PDQ-39), the "Zarit" scale and the Clinical Global Impression of Change, Independence Scale, Mattis score, MMSE
- Gait: time and number of steps and freezing at the Stand Walk Sit test, the Tinetti scale, the UPDRS I, II, III et IV, the self questionnaire of Giladi
- Sleep quality: during two successive polysomnography recordings (sleep pattern, measures of the rapid eye movement (REM) sleep time, daytime sleepiness (PDSS and Epworth), and Sleep Latency Test
- Magnetic Resonance Spectroscopy on the measures of the choline/creatine and glutamate/creatine peaks (medial frontal cortex, limbic cortex, caudate nucleus, putamen, pedunculopontine nucleus) on 3 Tesla MRI
Safety and Tolerability Endpoints (V1, V3 and V6):
Safety and tolerability will be evaluated with reference to the following:
Tolerability :
Number of subjects (%) who discontinue the study, Number of subjects (%) who discontinue the study due to AEs.
- Safety Measures :
AE incidence, Safety laboratory values, Vital signs, Blood pressure monitoring, ECG, Physical and neurological examination.
Study Design
Multicentric pilot study: 36-week double blind, placebo-controlled phase. After being found eligible to participate in the study, subjects will be allocated in a 1:1 ratio into one of the following two treatment groups based on a randomization scheme with blocks stratified:
- one patch of 4.6 mg/day during 1 month, then one patch of 9.5 mg/day during 5 months
- one patch of placebo during 6 months
Schedule: 7 visits
- Four consultations: screening (V0), randomisation (V1, 15 days after V0), (V3) visit after 3 months and termination (V7, 6 months after randomisation)
- Two phone calls (V2, V4)
Patients :
60 subjects with Parkinson's disease duration of more than 5 years, without dementia (Mattis Dementia Rating Scale ≥ 130, MMSE ≥ 27 and DSM IV), without major depression (MADRS < 18) who have developed apathy (defined by a score of - 16 or more at the LARS) despite an optimal dopaminergic treatment No additional therapy will be permitted during the study.
Investigational Medicinal Product (IMP) & Dosage:
Rivastigmine, or matching placebo, administered by transdermal patch a day in the morning:
4.6 mg a day during one month, 9.5 mg a day during five months
Centres :
Lille :
- Department of Neurology, University Hospital, Lille : Pr L. Defebvre, Pr K. Dujardin, Dr D. Devos, Pr Destee, Mme Delliaux. Dr A Kreisler, Dr C Simonin, Dr C. Moreau
- Department of Pharmacology, Faculté de Médecine, Lille II : R. Bordet
- Department of Clinical Neurophysiology, sleep laboratory : Pr P. Derambure, Dr C. Monaca
- Department of Neuroradiology : Pr J. Pruvo Dr C. Delmaire Dr P. Jissendi, Dr G. Soto Ares, Pr X. Leclerc
- Department of Statistics, CERIM, Faculté de Médecine Lille II : Dr P. Devos, Dr A. Duamel
- Lille III University : Dr P. Sockeel Méthodologiste
Amiens :
- Department of Neurology, University Hospital, Amiens : Pr P. Krystkowiak, Pr O. Godefroy, Dr Gérard, Dr Dupuy, Pr Deramon, Pr JM Macron, Dr Rose
Rouen :
- Department of Neurology, University Hospital, Rouen, . Dr D. Maltête, Pr. D. Hannequin, Dr. O. Martinaud, Dr E. Gérardin, Pr. B. Mihout, Mmes C. Aubier-Girard, S Bioux, E. Bliaux, D. Pouliquen
Caen :
- Department of Neurology, University Hospital,Caen, : Pr G. Defer, Pr F. Viader, Dr Guillamo Dr Marié, Dr Carluer, Mme Lebrun
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Nord
-
Lille, Nord, France, 59037
- Devos
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion criteria:
- Clinical diagnosis of Parkinson's disease: Gibb and Gelb criteria
- Apathy defined by a score of - 16 or more on the LARS scale (Sockeel et al., 2006)and criteria of Marin (1991)
- No dementia according to DSM IV with MMSE Score≥ 27 and Mattis score≥ 130
- Under stable dopaminergic treatment for 3 months
Exclusion criteria:
- Depression according to DSM-IV criteria and a score < 18 on the MADRS
- Subthalamic stimulation of less than one year
- Subthalamic stimulation without stable parameters for 3 months
- Subject older than 80 years
- Severe rest tremor with a subscore > or= 3 on the UPDRS part
- Parkinson related Psychosis in progress
- Hypersensibility to cholinesterase inhibitors or carbamates
- Myocardial infarction, other cardiac affections
- Severe hepatic insufficiency
- Sever medical illness
- Skin diseases interfering with transdermal patch
- Pregnancy
- Incapacity to give the consent
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Active treatment
A: transdermal rivastigmine at 4.6 mg per day during one month then 9.5 mg per day during 5 months.
|
transdermal patch of rivastigmine of 9.5 mg/day
Other Names:
|
Placebo Comparator: placebo
transdermal patch of placebo
|
transdermal patch of placebo
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Measure on the scale : Lille Apathy Rating Scale (LARS)
Time Frame: 6 months
|
measure of the reduction of apathy with this qualitative scale from -36 +36 with the cut off -16
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Cognitive, motor and behaviour assessment
Time Frame: 6 months
|
6 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: David Devos, MD, PhD, Department of Neurology, University Hospital, Lille
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurocognitive Disorders
- Parkinsonian Disorders
- Basal Ganglia Diseases
- Movement Disorders
- Synucleinopathies
- Neurodegenerative Diseases
- Parkinson Disease
- Dementia
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Cholinergic Agents
- Enzyme Inhibitors
- Neuroprotective Agents
- Protective Agents
- Rivastigmine
- Cholinesterase Inhibitors
Other Study ID Numbers
- 2008-002578-36
- 2008/0817 (Other Identifier: sponsor)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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