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

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

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).

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Memantine

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 Type: Interventional
• Enrollment (Anticipated): 26
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Department of Psychogeriatrics，Shanghai Mental Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Memantine	Drug: Memantine; Initially memantine 5mg/day, titrated within the first month to a maintenance dose of 20mg/day; Other Names: Memantine hydrochloride

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center
• Collaborators: H. Lundbeck A/S
• Investigators: Principal Investigator: Shifu Xiao, MD. PhD., Department of Psychogeriatrics，Shanghai Mental Health Center

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: October 23, 2008
• First Submitted That Met QC Criteria: December 1, 2008
• First Posted (Estimate): December 2, 2008

Study Record Updates

• Last Update Posted (Estimate): December 3, 2010
• Last Update Submitted That Met QC Criteria: December 2, 2010
• Last Verified: December 1, 2010

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; PET; Memantine; tau protein
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Memantine
• Other Study ID Numbers: IIT_12484A