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

Alzheimer's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00800709
• Other study ID #: IIT_12484A
• Status: Completed
• Phase: Phase 4
• First received: October 23, 2008
• Last updated: December 2, 2010
• Start date: July 2008
• Est. completion date: October 2010

Study information

• Verified date: December 2010
• Source: Shanghai Mental Health Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: October 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years to 90 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

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

Locations

Country	Name	City	State
China	Department of Psychogeriatrics,Shanghai Mental Health Center	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai Mental Health Center	H. Lundbeck A/S

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	biological markers of CSF		24 weeks	No
Primary	18[F]-FDG-PET of brain		24 weeks	No
Primary	cognitive function		24 weeks	No
Secondary	behavior and activities of daily living		24 weeks	No
Secondary	short term memory		24 weeks	No