Efficacy and Tolerability of Memantine in Frontotemporal Dementia (FTD) Patients
|First Received Date ICMJE||September 12, 2005|
|Last Updated Date||May 2, 2013|
|Start Date ICMJE||September 2005|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00200538 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Efficacy and Tolerability of Memantine in Frontotemporal Dementia (FTD) Patients|
|Official Title ICMJE||Double-blind, Parallel Group, Placebo-controlled Trial of the Efficacy and Tolerability of Memantine (20 mg) in Frontotemporal Dementia (FTD) Patients|
The purpose of this trial is to assess the efficacy and tolerability of memantine (anti-excitotoxic, neuroprotective treatment currently used in Alzheimer's disease [AD]) in frontotemporal dementia patients after a one-year treatment.
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 Alzheimer's 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:
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 1:1) twice a day (i.e., 20 mg of memantine per day in the memantine arm). The primary efficacy variable will be a global assessment tool, the CIBIC-Plus (Clinician's 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 Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Intervention ICMJE||Drug: memantine|
|Study Arm (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||45 Years to 75 Years|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||France|
|NCT Number ICMJE||NCT00200538|
|Other Study ID Numbers ICMJE||BRD 05/1-E|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||Nantes University Hospital|
|Collaborators ICMJE||Not Provided|
|Information Provided By||Nantes University Hospital|
|Verification Date||January 2005|
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