Double-blind, Parallel Group, Placebo-controlled Trial of the Efficacy and Tolerability of Memantine (20 mg) in Frontotemporal Dementia (FTD) Patients

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:

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 3,500 vs 600,000, for AD, in France in 2004-, FTD therefore falls into the category of rare diseases (i.e., less than 30,000 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.