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

August 29, 2012 updated by: H. Lundbeck A/S

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

277

Phase

  • Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: Placebo
Drug: Placebo
Tablets twice daily
EXPERIMENTAL: Memantine
Drug: Memantine
10 mg tablets twice daily
Other Names:
  • Ebixa®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Brain Atrophy Rate Estimated Using Brain Boundary Shift Integral (BBSI)
Time Frame: Baseline to 1 year
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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Total Hippocampal Volume (HCV)
Time Frame: Baseline to 1 year
Estimated mean changes in total HCV
Baseline to 1 year
Cognitive and Behavioural Outcomes: Controlled Oral Word Association Test (COWAT) Total Score
Time Frame: Baseline to 1 year
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
Cognitive and Behavioural Outcomes: Mini Mental State Examination (MMSE) Total Score
Time Frame: Baseline to 1 year
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

H. Lundbeck A/S

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Primary Completion (ACTUAL)

February 1, 2009

Study Completion (ACTUAL)

April 1, 2009

Study Registration Dates

First Submitted

March 16, 2009

First Submitted That Met QC Criteria

March 16, 2009

First Posted (ESTIMATE)

March 17, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

September 3, 2012

Last Update Submitted That Met QC Criteria

August 29, 2012

Last Verified

August 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 10112 (DAIDS-ES)
  • 2004-002614-10 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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