Ignite Creation Date:
2024-05-05 @ 10:25 PM
Last Modification Date:
2024-10-26 @ 10:18 AM
Study NCT ID:
NCT01108029
Status:
COMPLETED
Last Update Posted:
2012-03-26
First Post:
2009-07-20
Brief Title:
Study of Memantine for Gait Disorders And Attention Deficit In Parkinsons Disease
Sponsor:
University Hospital Lille
Organization:
University Hospital Lille
Study Overview
Official Title:
Study of Memantine to Treat Gait Disorders And Attention Deficit In Parkinsons Disease A Randomized Double-Blind Placebo-Controlled Parallel-Group Monocentric Trial
Status:
COMPLETED
Status Verified Date:
2009-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
FOGG-I
Brief Summary:
Along with cognitive and psychobehavioural disorders gait disorders represent a major problem in the treatment of advanced Parkinsons disease PD PD can be considered to be a hyperglutamatergic disease because dopaminergic depletion induces hyperactivity of the subthalamic nucleus STN and the internal pallidum GPi with glutamatergic hyperactivity of the STNs efferent pathway ie the subthalamopallidal subthalamonigral and subthalamo-entopeduncular pathways projecting to the pedunculopontine nucleus PPN Excess glutamate in the PPN has also been observed in the 6-OHDA rat model of PD Reduction of this glutamatergic hyperactivity within the PPN via the systemic or intra-peduncular administration of glutamate antagonists improves akinesia in drug-induced murine and primate models of PD via the NMDA and AMPA receptors High doses of memantine 10 mgkg improve locomotion in reserpine- and alpha-methyl-p-tyrosine-treated rats In humans the PPN may play a key role in gait posture control axial rigidity and attention It is also involved in the gating of sensory information involved in the startle reflex which can be studied via prepulse inhibition PPI of the blink reflex At present two uncompetitive NMDA receptor antagonists are approved for use in humans amantadine and memantine Reviews of the recent literature on these drugs have identified no published studies specifically on severe gait and attention disorders in PD Memantine is a partial blocker of open NMDA channels The value of memantine relates to the fact that it decreases excessive glutamatergic transmission by lowering the synaptic noise due to excessive activation of NMDA receptors In this double-blind study the investigators shall seek to demonstrate the presence or absence of an effect of memantine on gait and attention disorders In order to study the interaction between glutamatergic hyperactivity and the dopaminergic system the investigators shall study the phenomena both in the absence of L-dopa and following acute administration of the latter Twenty eight volunteer non-demented late-stage PD patients displaying severe gait disorders will receive memantine 20 mgday or placebo for 3 months The investigators expect to see a reduction in gait and attention disorders together with an improvement in the blink reflex with PPI under memantine This pilot study could subsequently be turned into a double-blind placebo-controlled multicenter study
Detailed Description:
Overall study duration 2 years Planned inclusion period 12 months Study duration for individual patients 4 months and 2 weeks2 weeks between screening and randomization 3 months of double-blind treatment and then a 4-week wash-out period
Primary objective V1 and V4
To assess efficacy of memantine treatment on severe gait disorders assessed on stride length by gait analysis with an optoelectronic system VICON in patients with advanced Parkinsons disease under subthalamic stimulation
Additional Efficacy Endpoints V1 and V4
Kinematic and Kinetic parameters stride length stride time velocity and cadence of the gait initiation and the stabilized gait using the optoelectronic system VICON
Gait and motor symptoms the Freezing Of Gait trajectory the UPDRS scores part III the dyskinesia rating scale
Axial rigidity measured by passive flexion on isokinetic dynamometer Cybex 6000
Axial strength measured by active flexion on isokinetic dynamometer Cybex 6000
Attention simple and complex reactions times
The inhibition of the presynaptic dopamine transporter by memantine was assessed by the mean DAT density of the bilateral striatum putamen and caudate nuclei using 99mTcTRODAT-1 SPECT
Safety and Tolerability Endpoints V1 V2 V3 and V4
Drowsiness Epworth and Parkinsons disease Sleep Scales
Apathy Lille Apathy Rating Scale
Depression MADRS
Pharmacokinetic properties of memantine were analyzed by the lowest plasmatic concentrations of memantine before the morning intake of the blinded treatment at 700 h during the steady state after 3 months blind secondary analyse
Safety Recording of all serious and non serious adverse events reported by the patients electrocardiogram blood pressure and biological analyzes blood counts ionogram urea creatinemia transaminases alkaline phosphatase bilirubinemia gamma GT magnesium
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
Monocentric study 12-week double blind placebo-controlled phase After being found eligible to participate in the study subjects will be allocated in a 11 ratio into one of the following two treatment groups based on a randomization scheme with blocks stratified
one memantine
1 st week 5 mg per day in the morning
2 nd week 10 mg per day in the morning
3 rd week 15 mg per day in the morning
4 th week 20 mg per day in the morning
one placebo during 3 months same as memantine
Schedule 5 visits screening V0 randomization V1 15 days after V0 V2 visit after 1 months V3 visit after 2 months and termination V4 3 months after randomization
Patients 28 subjects with Parkinsons 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 severe gait disorders including freezing of gait defined by an answer 2 or 3 at the 3rd question of the autoquestionnaire of Giladi Do your gait disorders impede your daily living activities and your independence answer yes moderately or severely But the patient requires no physical assistance to walk despite an optimal dopaminergic treatment and optimal and stable subthalamic stimulation parameters No additional therapy will be permitted during the study
Centre LILLE
Department of Neurology University Hospital of Lille Pr L Defebvre Pr K Dujardin Dr D Devos Pr Destee Mme Delliaux Dr A Kreisler Dr C Simonin Dr C Moreau Dr A Delval Department of Pharmacology Faculté de Médecine Lille II
Primary objective V1 and V4
To assess efficacy of memantine treatment on severe gait disorders assessed on stride length by gait analysis with an optoelectronic system VICON in patients with advanced Parkinsons disease under subthalamic stimulation
Additional Efficacy Endpoints V1 and V4
Kinematic and Kinetic parameters stride length stride time velocity and cadence of the gait initiation and the stabilized gait using the optoelectronic system VICON
Gait and motor symptoms the Freezing Of Gait trajectory the UPDRS scores part III the dyskinesia rating scale
Axial rigidity measured by passive flexion on isokinetic dynamometer Cybex 6000
Axial strength measured by active flexion on isokinetic dynamometer Cybex 6000
Attention simple and complex reactions times
The inhibition of the presynaptic dopamine transporter by memantine was assessed by the mean DAT density of the bilateral striatum putamen and caudate nuclei using 99mTcTRODAT-1 SPECT
Safety and Tolerability Endpoints V1 V2 V3 and V4
Drowsiness Epworth and Parkinsons disease Sleep Scales
Apathy Lille Apathy Rating Scale
Depression MADRS
Pharmacokinetic properties of memantine were analyzed by the lowest plasmatic concentrations of memantine before the morning intake of the blinded treatment at 700 h during the steady state after 3 months blind secondary analyse
Safety Recording of all serious and non serious adverse events reported by the patients electrocardiogram blood pressure and biological analyzes blood counts ionogram urea creatinemia transaminases alkaline phosphatase bilirubinemia gamma GT magnesium
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
Monocentric study 12-week double blind placebo-controlled phase After being found eligible to participate in the study subjects will be allocated in a 11 ratio into one of the following two treatment groups based on a randomization scheme with blocks stratified
one memantine
1 st week 5 mg per day in the morning
2 nd week 10 mg per day in the morning
3 rd week 15 mg per day in the morning
4 th week 20 mg per day in the morning
one placebo during 3 months same as memantine
Schedule 5 visits screening V0 randomization V1 15 days after V0 V2 visit after 1 months V3 visit after 2 months and termination V4 3 months after randomization
Patients 28 subjects with Parkinsons 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 severe gait disorders including freezing of gait defined by an answer 2 or 3 at the 3rd question of the autoquestionnaire of Giladi Do your gait disorders impede your daily living activities and your independence answer yes moderately or severely But the patient requires no physical assistance to walk despite an optimal dopaminergic treatment and optimal and stable subthalamic stimulation parameters No additional therapy will be permitted during the study
Centre LILLE
Department of Neurology University Hospital of Lille Pr L Defebvre Pr K Dujardin Dr D Devos Pr Destee Mme Delliaux Dr A Kreisler Dr C Simonin Dr C Moreau Dr A Delval Department of Pharmacology Faculté de Médecine Lille II
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2008_020841 | OTHER | sponsor | None |