Memantine and Changes of Biological Markers and Brain PET Imaging in Alzheimer's Disease
Information source: Shanghai Mental Health Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Alzheimer's Disease
Intervention: Memantine (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Shanghai Mental Health Center Official(s) and/or principal investigator(s):
Shifu Xiao, MD. PhD., Principal Investigator, Affiliation: Department of Psychogeriatrics，Shanghai Mental Health Center
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 Details
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
Study design: Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: biological markers of CSF18[F]-FDG-PET of brain cognitive function
Secondary outcome: behavior and activities of daily livingshort term memory
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.
Eligibility
Minimum age: 50 Years.
Maximum age: 90 Years.
Gender(s): Both.
Criteria:
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.
Locations and Contacts
Department of Psychogeriatrics，Shanghai Mental Health Center, Shanghai, Shanghai 200030, China
Additional Information
Starting date: July 2008
Last updated: December 2, 2010
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