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

NCT00800709 | Completed Phase 4 DMC

• 1 other identifier: IIT_12484A
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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).

Conditions

Alzheimer's Disease

Keywords

Alzheimer's Disease; tau protein; PET; Memantine

Outcome Measures

Primary Outcomes (3)

• biological markers of CSF

  24 weeks

• 18[F]-FDG-PET of brain

  24 weeks

• cognitive function

  24 weeks

Secondary Outcomes (2)

• behavior and activities of daily living

  24 weeks

• short term memory

  24 weeks

Study Arms (1)

Memantine

EXPERIMENTAL

Drug: Memantine

Interventions

Memantine DRUG

Initially memantine 5mg/day, titrated within the first month to a maintenance dose of 20mg/day

Also known as: Memantine hydrochloride

Memantine

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Shanghai Mental Health Center: lead
• H. Lundbeck A/S: collaborator

Study Sites (1)

Department of Psychogeriatrics，Shanghai Mental Health Center

Shanghai, Shanghai Municipality, 200030, China

Location

MeSH Terms

Conditions

Alzheimer Disease; Frontotemporal Dementia

Interventions

Memantine

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Frontotemporal Lobar Degeneration; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Shifu Xiao, MD. PhD.

  Department of Psychogeriatrics，Shanghai Mental Health Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 23, 2008
• First Posted: December 2, 2008
• Study Start: July 1, 2008
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: December 3, 2010

Record last verified: 2010-12

Locations

CN (1)