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

Primary Purpose

Alzheimer's Disease

Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Memantine
Placebo
Sponsored by
H. Lundbeck A/S
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer's Disease focused on measuring Memantine, Neuroimaging, MRI, Brain atrophy

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Memantine

    Placebo

    Arm Description

    Outcomes

    Primary Outcome Measures

    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)

    Secondary Outcome Measures

    Changes in Total Hippocampal Volume (HCV)
    Estimated mean changes in total HCV
    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
    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

    Full Information

    First Posted
    March 16, 2009
    Last Updated
    August 29, 2012
    Sponsor
    H. Lundbeck A/S
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00862940
    Brief Title
    A Clinical Study Evaluating the Effects of Memantine on Brain Atrophy in Patients With Alzheimer's Disease
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2012
    Overall Recruitment Status
    Completed
    Study Start Date
    September 2005 (undefined)
    Primary Completion Date
    February 2009 (Actual)
    Study Completion Date
    April 2009 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    H. Lundbeck A/S

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief 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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Alzheimer's Disease
    Keywords
    Memantine, Neuroimaging, MRI, Brain atrophy

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    277 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Memantine
    Arm Type
    Experimental
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Intervention Type
    Drug
    Intervention Name(s)
    Memantine
    Other Intervention Name(s)
    Ebixa®
    Intervention Description
    10 mg tablets twice daily
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Tablets twice daily
    Primary Outcome Measure Information:
    Title
    Total Brain Atrophy Rate Estimated Using Brain Boundary Shift Integral (BBSI)
    Description
    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)
    Time Frame
    Baseline to 1 year
    Secondary Outcome Measure Information:
    Title
    Changes in Total Hippocampal Volume (HCV)
    Description
    Estimated mean changes in total HCV
    Time Frame
    Baseline to 1 year
    Title
    Cognitive and Behavioural Outcomes: Controlled Oral Word Association Test (COWAT) Total Score
    Description
    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
    Time Frame
    Baseline to 1 year
    Title
    Cognitive and Behavioural Outcomes: Mini Mental State Examination (MMSE) Total Score
    Description
    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
    Time Frame
    Baseline to 1 year

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    50 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Email contact via H. Lundbeck A/S
    Organizational Affiliation
    LundbeckClinicalTrials@lundbeck.com
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    22269160
    Citation
    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.
    Results Reference
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    A Clinical Study Evaluating the Effects of Memantine on Brain Atrophy in Patients With Alzheimer's Disease

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