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

Phase 4

Completed

• Conditions: Alzheimer's Disease
• Interventions: Drug: Memantine

• Registration Number: NCT00800709
• Lead Sponsor: Shanghai Mental Health Center

Brief 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).

Detailed 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 Timeline

• Study Start: 2008-07
• Study First Submitted: 2008-10-23
• Study First Submitted QC: 2008-12-01
• Study First Posted: 2008-12-02
• Primary Completion: 2010-10
• Study Completion: 2010-10
• Status Verified: 2010-12
• Last Update Submitted: 2010-12-02
• Last Update Posted: 2010-12-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

1. Written informed consent
2. Clinical diagnosis of Alzheimer's disease which meet the DSM-IV criteria.
3. Subject has moderate to severe Alzheimer's disease as defined by a MMSE score 4 to 20 inclusive at screening.
4. Hachinski Ischemia Score < 4 at screening.
5. Age ≥50 and ≤90 years.
6. Availability of a responsible and steady caregiver to ensure treatment compliance and provide information for assessments.

Exclusion Criteria

1. Severe renal impairment.
2. History of seizures
3. Systolic blood pressure >160 or < 90 mmHg or diastolic blood pressure > 95 or < 60 mmHg at the time of screening.
4. Diagnosis of any concomitant life threatening illness.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Memantine	Memantine	-

Primary Outcome Measures

Name	Time	Method
biological markers of CSF	24 weeks
18[F]-FDG-PET of brain	24 weeks
cognitive function	24 weeks

Secondary Outcome Measures

Name	Time	Method
behavior and activities of daily living	24 weeks
short term memory	24 weeks

Trial Locations

Locations (1)

Department of Psychogeriatrics，Shanghai Mental Health Center; 🇨🇳 Shanghai, Shanghai, China