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

This study has been completed.
Sponsor:
Collaborator:
H. Lundbeck A/S
Information provided by:
Shanghai Mental Health Center
ClinicalTrials.gov Identifier:
NCT00800709
First received: October 23, 2008
Last updated: December 2, 2010
Last verified: December 2010
  Purpose

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).


Condition Intervention Phase
Alzheimer's Disease
Drug: Memantine
Phase 4

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

Resource links provided by NLM:


Further study details as provided by Shanghai Mental Health Center:

Primary Outcome Measures:
  • biological markers of CSF [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • 18[F]-FDG-PET of brain [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • cognitive function [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • behavior and activities of daily living [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • short term memory [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 26
Study Start Date: July 2008
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Memantine Drug: Memantine
Initially memantine 5mg/day, titrated within the first month to a maintenance dose of 20mg/day
Other Name: Memantine hydrochloride

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

Ages Eligible for Study:   50 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00800709

Locations
China, Shanghai
Department of Psychogeriatrics,Shanghai Mental Health Center
Shanghai, Shanghai, China, 200030
Sponsors and Collaborators
Shanghai Mental Health Center
H. Lundbeck A/S
Investigators
Principal Investigator: Shifu Xiao, MD. PhD. Department of Psychogeriatrics,Shanghai Mental Health Center
  More Information

No publications provided

Responsible Party: Department of Psychogeriatrics, Shanghai Mental Health Center, Shanghai Mental Heath Center
ClinicalTrials.gov Identifier: NCT00800709     History of Changes
Other Study ID Numbers: IIT_12484A
Study First Received: October 23, 2008
Last Updated: December 2, 2010
Health Authority: China: Ethics Committee

Keywords provided by Shanghai Mental Health Center:
Alzheimer's Disease
tau protein
PET
Memantine

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Memantine
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014