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

Alzheimer's Disease Clinical Trial

Official title: 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

Status Completed

Clinical Trial Summary

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).

Clinical Trial Description

1. To investigate the effects of daily dosing of memantine for 24 weeks versus placebo on biological markers of subjects with Alzheimer's disease.

2. 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.

3. To investigate the effects of daily dosing of memantine for 24 weeks versus placebo on cognitive function in subjects with Alzheimer's disease.

4. 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.

5. To investigate the effects of daily dosing of memantine for 24 weeks versus placebo on short term memory. ;

Study Design

Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

• NCT number: NCT00800709
• Study type: Interventional
• Source: Shanghai Mental Health Center
• Status: Completed
• Phase: Phase 4
• Start date: July 2008
• Completion date: October 2010