Trial record 1 of 208 for:    Cerebral Atrophy
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A Clinical Study Evaluating the Effects of Memantine on Brain Atrophy in Patients With Alzheimer's Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
H. Lundbeck A/S
ClinicalTrials.gov Identifier:
NCT00862940
First received: March 16, 2009
Last updated: August 29, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Alzheimer's Disease
Drug: Memantine
Drug: Placebo
Phase 4

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

Resource links provided by NLM:


Further study details as provided by H. Lundbeck A/S:

Primary Outcome Measures:
  • Total Brain Atrophy Rate Estimated Using Brain Boundary Shift Integral (BBSI) [ Time Frame: Baseline to 1 year ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline to 1 year ] [ Designated as safety issue: No ]
    Estimated mean changes in total HCV

  • Cognitive and Behavioural Outcomes: Controlled Oral Word Association Test (COWAT) Total Score [ Time Frame: Baseline to 1 year ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to 1 year ] [ Designated as safety issue: No ]
    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


Enrollment: 277
Study Start Date: September 2005
Study Completion Date: April 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Memantine Drug: Memantine
10 mg tablets twice daily
Other Name: Ebixa®
Placebo Comparator: Placebo Drug: Placebo
Tablets twice daily

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.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00862940

Sponsors and Collaborators
H. Lundbeck A/S
Investigators
Study Director: Email contact via H. Lundbeck A/S LundbeckClinicalTrials@lundbeck.com
  More Information

Publications:
Responsible Party: H. Lundbeck A/S
ClinicalTrials.gov Identifier: NCT00862940     History of Changes
Other Study ID Numbers: 10112, 2004-002614-10
Study First Received: March 16, 2009
Results First Received: November 23, 2010
Last Updated: August 29, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by H. Lundbeck A/S:
Memantine
Neuroimaging
MRI
Brain atrophy

Additional relevant MeSH terms:
Atrophy
Brain Diseases
Alzheimer Disease
Dementia
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Pathological Conditions, Anatomical
Memantine
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents

ClinicalTrials.gov processed this record on August 21, 2014