Ignite Creation Date:
2024-05-05 @ 12:00 PM
Last Modification Date:
2024-10-26 @ 9:18 AM
Study NCT ID:
NCT00200538
Status:
COMPLETED
Last Update Posted:
2013-05-03
First Post:
2005-09-12
Brief Title:
Efficacy and Tolerability of Memantine in Frontotemporal Dementia FTD Patients
Sponsor:
Nantes University Hospital
Organization:
Nantes University Hospital
Study Overview
Official Title:
Double-blind Parallel Group Placebo-controlled Trial of the Efficacy and Tolerability of Memantine 20 mg in Frontotemporal Dementia FTD Patients
Status:
COMPLETED
Status Verified Date:
2005-01
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:
None
Brief Summary:
The purpose of this trial is to assess the efficacy and tolerability of memantine anti-excitotoxic neuroprotective treatment currently used in Alzheimers disease AD in frontotemporal dementia patients after a one-year treatment
Detailed Description:
Background Frontotemporal dementia FTD is the first cause of dementia in the presenium onset before the age of 65 years Characterized by behavioral disorders it is often more incapacitating than Alzheimers disease AD and leads to death within 7 years on average 9-10 years for AD It affects young individuals on average 20 years younger than in AD who are often still active Management of these patients is therefore burdensome and complex As opposed to AD however no treatment is currently available Few therapeutic trials have actually been conducted on this disorder Many reasons may account for this
1 recent availability of reliable diagnostic criteria the Lund and Manchester groups consensus statement in 1994 revised in 1998
2 the very small number of cases as opposed to AD-the number of cases was estimated at approximately 3500 vs 600000 for AD in France in 2004- FTD therefore falls into the category of rare diseases ie less than 30000 cases
3 the scarcity of valuable physiopathological hypotheses
Besides a non-specific serotoninergic dysfunction no significant anomalies related to particular neuromediators have apparently been found as opposed to AD which is characterized by a cholinergic deficit In 1998 the discovery of mutations in the Tau gene in certain kindreds showing a dominant autosomal transmission of FTD oriented research efforts toward the tau protein and provided new perspectives Many studies have suggested the role of excitotoxicity Abnormal aggregation of the tau protein has been observed in the brains of a majority of FTD patients familial and sporadic form Excitotoxicity may be responsible for promoting this abnormal aggregation through modification of the expression and phosphorylation state of the tau protein The hypothesis of this study is that an anti-excitotoxic neuroprotective treatment may slow the pathogenic process and therefore be an effective treatment for this pathology
Goals To assess the efficacy and tolerability of memantine anti-excitotoxic neuroprotective treatment currently used in AD in FTD patients after a one-year treatment
Type of study National multicenter randomized double-blind parallel group placebo-controlled phase II therapeutic trial
Study design Sixty four 64 patients aged 45 to 75 years will be enrolled in the study for a period of 12 months clinical inclusion criteria are defined based on the Lund and Manchester group consensus statement revised version 1998 and followed up for 1 year in a controlled study At the time of inclusion the Mini Mental Status Examination MMSE score should be at least 19 below 18 a neuropsychological examination is impossible Patients will either take memantine or a placebo randomization ratio of 11 twice a day ie 20 mg of memantine per day in the memantine arm The primary efficacy variable will be a global assessment tool the CIBIC-Plus Clinicians Interview-Based Impression of Change Plus Caregiver Input Secondary efficacy variables will include behavioral scales the NeuroPsychiatric Inventory NPI the Frontal Behavior Inventory FBI cognitive scales the Mattis Dementia Rating Scale MDRS the MMSE activities of daily living Disability Assessment for Dementia DAD time spent by the caregiver of the patient Resource Utilization in Dementia RUD and caregiver burden scale Zarit Burden Inventory and tolerability of the drug The main analysis will be carried out on an intention-to-treat basis in all randomized patients having undergone at least one evaluation after inclusion the Last Observation Carried Forward LOCF value will be attributed to missing values This analysis will be carried out at the end of the double-blind study main judgement criterion
Expected results and perspectives The main expected result is the confirmation of the efficacy of memantine as a treatment for FTD which would set a precedent in the treatment of this disease Such a result could also lead the way to the development of treatments for other related neurodegenerative disorders tauopathies such as the other frontotemporal lobar degenerations semantic dementia progressive non-fluent aphasia progressive supranuclear palsy or corticobasal degeneration Finally the standardized follow-up of a 64 patient cohort in this study will provide important information on the natural history of a rare and poorly-known disease
1 recent availability of reliable diagnostic criteria the Lund and Manchester groups consensus statement in 1994 revised in 1998
2 the very small number of cases as opposed to AD-the number of cases was estimated at approximately 3500 vs 600000 for AD in France in 2004- FTD therefore falls into the category of rare diseases ie less than 30000 cases
3 the scarcity of valuable physiopathological hypotheses
Besides a non-specific serotoninergic dysfunction no significant anomalies related to particular neuromediators have apparently been found as opposed to AD which is characterized by a cholinergic deficit In 1998 the discovery of mutations in the Tau gene in certain kindreds showing a dominant autosomal transmission of FTD oriented research efforts toward the tau protein and provided new perspectives Many studies have suggested the role of excitotoxicity Abnormal aggregation of the tau protein has been observed in the brains of a majority of FTD patients familial and sporadic form Excitotoxicity may be responsible for promoting this abnormal aggregation through modification of the expression and phosphorylation state of the tau protein The hypothesis of this study is that an anti-excitotoxic neuroprotective treatment may slow the pathogenic process and therefore be an effective treatment for this pathology
Goals To assess the efficacy and tolerability of memantine anti-excitotoxic neuroprotective treatment currently used in AD in FTD patients after a one-year treatment
Type of study National multicenter randomized double-blind parallel group placebo-controlled phase II therapeutic trial
Study design Sixty four 64 patients aged 45 to 75 years will be enrolled in the study for a period of 12 months clinical inclusion criteria are defined based on the Lund and Manchester group consensus statement revised version 1998 and followed up for 1 year in a controlled study At the time of inclusion the Mini Mental Status Examination MMSE score should be at least 19 below 18 a neuropsychological examination is impossible Patients will either take memantine or a placebo randomization ratio of 11 twice a day ie 20 mg of memantine per day in the memantine arm The primary efficacy variable will be a global assessment tool the CIBIC-Plus Clinicians Interview-Based Impression of Change Plus Caregiver Input Secondary efficacy variables will include behavioral scales the NeuroPsychiatric Inventory NPI the Frontal Behavior Inventory FBI cognitive scales the Mattis Dementia Rating Scale MDRS the MMSE activities of daily living Disability Assessment for Dementia DAD time spent by the caregiver of the patient Resource Utilization in Dementia RUD and caregiver burden scale Zarit Burden Inventory and tolerability of the drug The main analysis will be carried out on an intention-to-treat basis in all randomized patients having undergone at least one evaluation after inclusion the Last Observation Carried Forward LOCF value will be attributed to missing values This analysis will be carried out at the end of the double-blind study main judgement criterion
Expected results and perspectives The main expected result is the confirmation of the efficacy of memantine as a treatment for FTD which would set a precedent in the treatment of this disease Such a result could also lead the way to the development of treatments for other related neurodegenerative disorders tauopathies such as the other frontotemporal lobar degenerations semantic dementia progressive non-fluent aphasia progressive supranuclear palsy or corticobasal degeneration Finally the standardized follow-up of a 64 patient cohort in this study will provide important information on the natural history of a rare and poorly-known disease
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