Memantine and Changes of Biological Markers and Brain PET Imaging in Alzheimer's Disease

Study Overview
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Brief Summary
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In AD, tau protein is abnormally hyperphosphorylated. Significant changes of hyperphosphorylated tau levels in CSF are found in AD patients. It has been shown in vitro that memantine can reverse abnormal hyperphosphorylation of tau in hippocampal neurons of rats. A statistically significant reduction of CSF phosphorylated tau at a preliminary 1-year follow-up was observed, from median 126 (interquartile range 107-153) to 108 (88-133) ng/l (p = 0.018). No statistically significant differences of total tau or Aβ42 were found (Gunnarsson MD, 2007). FDG-PET has the unique ability to estimate the local cerebral metabolic rate of glucose consumption, thus providing information on the distribution of neuronal death and synapse dysfunction in AD in vivo (Herholz K. 2003). Synaptic dysfunction and loss induce a reduction in neuronal energy demand that results in decreased glucose metabolism. Hypometabolism in AD is thought to reflect loss of synaptic activity and density (Herholz K. 2003; Mielke R, et al. 1998). Another biological markers such as inflammatory factor and APOEε4 also play a part in the onset of AD (Glodzik-Sobanska L, 2007).

Detailed Description
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To investigate the effects of daily dosing of memantine for 24 weeks versus placebo on biological markers of subjects with Alzheimer's disease. To investigate the effects of daily dosing of memantine for 24 weeks versus placebo on 18[F]-FDG-PET of brain in subjects with Alzheimer's disease. To investigate the effects of daily dosing of memantine for 24 weeks versus placebo on cognitive function in subjects with Alzheimer's disease. To investigate the effects of daily dosing of memantine for 24 weeks versus placebo on measures of behavior and activities of daily living of subjects with Alzheimer's disease. To investigate the effects of daily dosing of memantine for 24 weeks versus placebo on short term memory.

Official Title
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Changes of Biological Markers and Brain PET Imaging and Clinical Effects of Memantine for Patients With Moderate to Severe Alzheimer's Disease: a 24 Week Double-blind, Randomized, Placebo-Controlled Study

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: Memantine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Clinical diagnosis of Alzheimer's disease which meet the DSM-IV criteria. Subject has moderate to severe Alzheimer's disease as defined by a MMSE score 4 to 20 inclusive at screening. Hachinski Ischemia Score < 4 at screening. Age ≥50 and ≤90 years. Availability of a responsible and steady caregiver to ensure treatment compliance and provide information for assessments. Exclusion Criteria: Severe renal impairment. History of seizures Systolic blood pressure >160 or < 90 mmHg or diastolic blood pressure > 95 or < 60 mmHg at the time of screening. Diagnosis of any concomitant life threatening illness.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Memantine<br> | Drug: Memantine<br>* Initially memantine 5mg/day, titrated within the first month to a maintenance dose of 20mg/day<br>* Other names: Memantine hydrochloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| biological markers of CSF |  | 24 weeks | 
| 18[F]-FDG-PET of brain |  | 24 weeks | 
| cognitive function |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| behavior and activities of daily living |  | 24 weeks | 
| short term memory |  | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's Disease, tau protein, PET, Memantine