A Clinical Study Evaluating the Effects of Memantine on Brain Atrophy in Patients With Alzheimer's Disease

Alzheimer's Disease Clinical Trial

Official title:

A 1-year Randomised, Double-blind Placebo-controlled Study to Evaluate the Effects of Memantine on Rate of Brain Atrophy in Patients With Alzheimer's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00862940
• Other study ID #: 10112
• Secondary ID: 2004-002614-10
• Status: Completed
• Phase: Phase 4
• First received: March 16, 2009
• Last updated: August 29, 2012
• Start date: September 2005
• Est. completion date: April 2009

Study information

• Verified date: August 2012
• Source: H. Lundbeck A/S
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesSwitzerland: SwissmedicUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

Pre-clinical studies have demonstrated that memantine can decrease the neuronal toxicity associated with excessive glutamate release and calcium overload in neurons. Previous studies have shown that memantine helps to treat the symptoms of Alzheimer's Disease (AD). In AD, the rate of brain tissue loss, or atrophy, is faster than in normal aging and this seems to go hand in hand with some of the symptoms of the disease. This suggests that memantine treatment in AD could provide both symptomatic improvement and neuro-protective effects. The purpose of this study was to show whether memantine, in addition to providing symptomatic benefits, can slow the rate of brain atrophy as assessed using magnetic resonance imaging (MRI) technology.

Description:

The primary objective of this study was to evaluate the effects of memantine on the rate of brain atrophy compared to placebo in patients with AD (moderate severity) over a 1-year period. This was a multinational, randomised, double-blind, parallel-group, placebo-controlled, fixed-dose study (20 mg memantine). The study also included secondary imaging, cognitive and behavioural measures.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 277
• Est. completion date: April 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Outpatients at least 50 years of age with a current diagnosis of probable AD of moderate severity (MMSE score between 12 and 20, inclusive) consistent with NINCDS-ADRDA criteria and MRI scans

• Patients must have had a knowledgeable and reliable caregiver to accompany them to all clinic visits during the study

• Patients were either on or off existing acetylcholinesterase inhibitor (AChEI) treatment provided that the treatment had been initiated >6 months prior to screening, had stabilised with respect to dose for >3 months, and remained fixed during the entire study. AChEI treatment could not be initiated or modified during the study

Exclusion Criteria:

• The patient had evidence of clinically significant active disease (including recent myocardial infarction and uncompensated congestive heart failure [NYHA II-IV])

• The patient had evidence of any clinically significant neurodegenerative disease or neurological disorder other than AD

• The patient was contraindicated for MRI

Other protocol-defined inclusion and exclusion criteria applied.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• Memantine
10 mg tablets twice daily
• Placebo
Tablets twice daily

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
H. Lundbeck A/S

References & Publications (1)

Wilkinson D, Fox NC, Barkhof F, Phul R, Lemming O, Scheltens P. Memantine and brain atrophy in Alzheimer's disease: a 1-year randomized controlled trial. J Alzheimers Dis. 2012;29(2):459-69. doi: 10.3233/JAD-2011-111616. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Brain Atrophy Rate Estimated Using Brain Boundary Shift Integral (BBSI)	Measures direct changes in total brain volume per visit interval (screening to Week 4, 42, or 52 or from Week 4 to Week 42 or 52)	Baseline to 1 year	No
Secondary	Changes in Total Hippocampal Volume (HCV)	Estimated mean changes in total HCV	Baseline to 1 year	No
Secondary	Cognitive and Behavioural Outcomes: Controlled Oral Word Association Test (COWAT) Total Score	Adjusted mean change from baseline on cognitive and behavioural scores. COWAT: Verbal fluency test. The patient was asked to, during 1 minute, generate as many words as possible beginning with three pre-specified letters. The total score was calculated as the sum of acceptable words generated, with higher scores indicating lower cognitive impairment	Baseline to 1 year	No
Secondary	Cognitive and Behavioural Outcomes: Mini Mental State Examination (MMSE) Total Score	Adjusted mean change from baseline on cognitive and behavioural scores. MMSE: Brief, structured examination of mental status that assesses orientation, memory, attention, naming, comprehension, and praxis. The range is 0 to 30, with a lower score indicating a worse mental state	Baseline to 1 year	No