Parkinson's DiseasePhase 3CHoPA-INCT00767091
Study of Rivastigmine to Treat Parkinsonian Apathy Without Dementia
A Phase 3 study testing rivastigmine in people with Parkinson's Disease and Apathy, run by University Hospital, Lille at 1 site in France.
Trial summary
Apathy usually refers to a set of behavioural, emotional and cognitive features as a reduced interest and participation in main activities of daily life, a lack of initiative, a trend toward an early withdrawal from started activities, an indifference and a flattening of affect. Read more about this study
- Who is it for?
- Ages 15 to 80 years
- Conditions the study is for
- Parkinson's Disease, Apathy, no Dementia
- What is being tested?
- rivastigmine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteFrance
- Study dates
- Mar 2009to Jan 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicentric Trial
Apathy usually refers to a set of behavioural, emotional and cognitive features as a reduced interest and participation in main activities of daily life, a lack of initiative, a trend toward an early withdrawal from started activities, an indifference and a flattening of affect. We have validated a new specific scale (Lille Apathy Rating Scale, LARS) in order to detect and quantify apathy in Parkinson's disease (PD). Apathy was shown to be frequent in PD with a prevalence of 32%. It has suggested that the medial frontal and limbic cholinergic deficits may underlie apathy in neurodegenerative disorders like Alzheimer's disease (AD). Such a hypothesis is supported by recent evidence indicating the beneficial effects of cholinesterase inhibitors on neuropsychiatric symptoms, mainly apathy, in AD patients. As the efficacy of rivastigmine on cognition has also been shown in PD, we aimed to assess with a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial, the efficacy and acceptability of a 6 months treatment with rivastigmine on apathy in 60 patients with PD without dementia. The primary end point will be the LARS score and the secondary end points will be the cognitive, behavioural and motor symptoms of PD. Two add-on studies will be proposed: first the measure of choline and glutamate peaks on Magnetic Resonance Spectrometry focused on the structures implicated in apathy in order to give insights in the physiopathological mechanisms of the treatment. Secondly, the recording of the REM sleep behavior disorders in relation with the cholinergic part of the pedunculopontine nucleus. Regarding that apathy could be one of the first steps toward PD dementia, treating very early could have substantial implications on the patients and their caregiver.
Read the 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
- Conditions
- Parkinson's Disease, Apathy, no Dementia
- Being tested
- rivastigmine, placebo
- Keywords
- Parkinson's disease, Apathy, Rivastigmine, transdermal patch, anticholinesterasic, acetylcholine
- Medical subject headings
- Parkinson Disease, Lethargy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rivastigmineDrug
Also called cholinesterase inhibitors (Exelon)
transdermal patch of rivastigmine of 9.5 mg/day
placeboDrug
Also called transdermal patch without active substance
transdermal patch of placebo
| Study group | Role | What they receive |
|---|---|---|
| Active treatment | Active comparator | A: transdermal rivastigmine at 4.6 mg per day during one month then 9.5 mg per day during 5 months. Receives: Drug: rivastigmine |
| placebo | Placebo comparator | transdermal patch of placebo Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measure on the scale : Lille Apathy Rating Scale (LARS)
measure of the reduction of apathy with this qualitative scale from -36 +36 with the cut off -16
Measured: 6 months
Secondary outcomes (1)
Cognitive, motor and behaviour assessment
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2008 (estimated)
- Study startMar 2009
- Primary completionDec 2011
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- More trials run by University Hospital, LilleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Lille
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Devos, MD, PhD, Principal investigator, Department of Neurology, University Hospital, Lille
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00767091
- Sponsor's protocol ID
- 2008-002578-36
- Other IDs
- 2008/0817, 2008
- Acronym
- CHoPA-I
- Status last verified
- Mar 2009
- First submitted
- 1 Sep 2008
- Last updated
- 24 Apr 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Devos D, Moreau C, Maltete D, Lefaucheur R, Kreisler A, Eusebio A, Defer G, Ouk T, Azulay JP, Krystkowiak P, Witjas T, Delliaux M, Destee A, Duhamel A, Bordet R, Defebvre L, Dujardin K. Rivastigmine in apathetic but dementia and depression-free patients with Parkinson's disease: a double-blind, placebo-controlled, randomised clinical trial. J Neurol Neurosurg Psychiatry. 2014 Jun;85(6):668-74. doi: 10.1136/jnnp-2013-306439. Epub 2013 Nov 11.
PubMed 24218528
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicentric Trial
- ClinicalTrials.gov ID
- NCT00767091
- Acronym / sponsor ID
- CHoPA-I / 2008-002578-36
- Conditions
- Parkinson's Disease, Apathy, no Dementia
- Keywords
- Parkinson's disease, Apathy, Rivastigmine, transdermal patch, anticholinesterasic, acetylcholine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University Hospital, LilleUniversity, hospital or other
- Study start
- Mar 2009
- Primary completion
- Dec 2011 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 6 Oct 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Apathy usually refers to a set of behavioural, emotional and cognitive features as a reduced interest and participation in main activities of daily life, a lack of initiative, a trend toward an early withdrawal from started activities, an indifference and a flattening of affect. We have validated a new specific scale (Lille Apathy Rating Scale, LARS) in order to detect and quantify apathy in Parkinson's disease (PD). Apathy was shown to be frequent in PD with a prevalence of 32%. It has suggested that the medial frontal and limbic cholinergic deficits may underlie apathy in neurodegenerative disorders like Alzheimer's disease (AD). Such a hypothesis is supported by recent evidence indicating the beneficial effects of cholinesterase inhibitors on neuropsychiatric symptoms, mainly apathy, in AD patients. As the efficacy of rivastigmine on cognition has also been shown in PD, we aimed to assess with a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial, the efficacy and acceptability of a 6 months treatment with rivastigmine on apathy in 60 patients with PD without dementia. The primary end point will be the LARS score and the secondary end points will be the cognitive, behavioural and motor symptoms of PD. Two add-on studies will be proposed: first the measure of choline and glutamate peaks on Magnetic Resonance Spectrometry focused on the structures implicated in apathy in order to give insights in the physiopathological mechanisms of the treatment. Secondly, the recording of the REM sleep behavior disorders in relation with the cholinergic part of the pedunculopontine nucleus. Regarding that apathy could be one of the first steps toward PD dementia, treating very early could have substantial implications on the patients and their caregiver.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active treatment | Active comparator | Drug: rivastigmineA: transdermal rivastigmine at 4.6 mg per day during one month then 9.5 mg per day during 5 months. |
| placebo | Placebo comparator | Drug: placebotransdermal patch of placebo |
Who may qualify
- Ages
- 15 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rivastigmineAlso: cholinesterase inhibitors (Exelon)transdermal patch of rivastigmine of 9.5 mg/day | Drug | Active treatment |
| placeboAlso: transdermal patch without active substancetransdermal patch of placebo | Drug | placebo |
Primary outcome
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
1 secondary outcome
Cognitive, motor and behaviour assessment
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2012.
- Derived from this study: PubMed 24218528Devos D, Moreau C, Maltete D, Lefaucheur R, Kreisler A, Eusebio A, Defer G, Ouk T, Azulay JP, Krystkowiak P, Witjas T, Delliaux M, Destee A, Duhamel A, Bordet R, Defebvre L, Dujardin K. Rivastigmine in apathetic but dementia and depression-free patients with Parkinson's disease: a double-blind, placebo-controlled, randomised clinical trial. J Neurol Neurosurg Psychiatry. 2014 Jun;85(6):668-74. doi: 10.1136/jnnp-2013-306439. Epub 2013 Nov 11.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Devos, MD, PhD principal investigator
Department of Neurology, University Hospital, Lille
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing rivastigmine in people with Parkinson's Disease and Apathy, run by University Hospital, Lille at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measure on the scale : Lille Apathy Rating Scale (LARS) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00767091, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2012.