Clinical trial NCT00857649: Efficacy and Safety of Memantine in Moderate to Severe Alzheimer's Disease
Official title: A Randomised, Double-Blind, Parallel-Group Study Examining the Efficacy and Safety of Memantine in Patients With Moderate to Severe Dementia of the Alzheimer's Type
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Alzheimer's Disease
Keywords: Alzheimer's Disease
Lead sponsor: H. Lundbeck A/S
Sponsor class: INDUSTRY
First posted: 2009-03-06
Enrollment: 369
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to examine the efficacy of memantine on cognition and behavioural symptoms in outpatients with moderate to severe dementia of the Alzheimer's type.

Detailed description: Memantine is a moderate affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. Pre-clinical studies have demonstrated that memantine can decrease the neuronal toxicity associated with excessive glutamate release and calcium overload in neurons. Results from clinical trials in patients with moderate to severe Alzheimer's Disease (AD) have demonstrated memantine's efficacy and safety by showing positive treatment effects on cognitive, global and functional decline.

This 24-week randomised, double-blind, placebo-controlled, multicentre study examines the effect of memantine 20 mg, administered once daily, on cognitive and behavioural symptoms in outpatients diagnosed with moderate to severe AD and significant psychopathology.

Eligibility criteria: Inclusion Criteria:

Outpatients who:

* had a primary diagnosis of probable Alzheimer's Disease (AD) according to National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINDS-ADRDA) criteria, and with Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revised (DSM IV TR) criteria for dementia of the Alzheimer's type
* had moderate to severe dementia, defined as a Mini Mental State Examination (MMSE) total score \>=5 and \<=15 at screening. Before substantial protocol amendment SA04 (dated 7 October 2004) was implemented, the MMSE total score range at screening was \>=8 and \<=18. Substantial protocol amendment SA07 (dated 4 September 2009) allowed patients who had previously had an MMSE score of 16 or 17 to be re-screened \>6 months after their initial screening and, if there was documented evidence of cognitive decline, to be enrolled in the study
* had a Neuropsychiatric Inventory (NPI) total score \>=13 and an NPI agitation/aggression subitem score \>=1 at screening and baseline
* did not have vascular dementia or a modified Hachinski Ischaemia Scale score \>4 at screening

Exclusion Criteria:

* Evidence of clinically significant active disease, evidence of other neurological disorders, and previous treatment with memantine

Primary outcomes:
measure: Efficacy of Memantine on Behavioural Symptoms in Outpatients With Moderate to Severe Dementia of the Alzheimer's Type Using the NPI - 12 Items Version Total Score.
timeFrame: Baseline to Week 24
measure: Efficacy of Memantine on Cognition in Outpatients With Moderate to Severe Dementia of the Alzheimer's Type Using the SIB Total Score.
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Efficacy of Memantine on Global Condition Using CIBIC-plus.
timeFrame: Baseline to Week 24
measure: Efficacy of Memantine on Functioning Using ADCS-ADL - 19 Items Total Score.
timeFrame: Baseline to Week 24
measure: Efficacy of Memantine on Functioning Using CMAI - Long Form Total Score.
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: CA019
state: Alberta
city: Kelowna
country: Canada
facility: CA033
state: British Columbia
city: Winnipeg
country: Canada
facility: CA034
state: Manitoba
city: St. John
country: Canada
facility: CA022
state: New Brunswick
city: Kentville
country: Canada
facility: CA046
state: Nova Scotia
city: Pictou
country: Canada
facility: CA045
state: Nova Scotia
city: Burlington
country: Canada
facility: CA032
state: Ontario
city: Orangeville
country: Canada
facility: CA029
state: Ontario
city: Ottawa
country: Canada
facility: CA004
state: Ontario
city: Peterborough
country: Canada
facility: CA038
state: Ontario
city: Toronto
country: Canada
facility: CA009
state: Ontario
city: Windsor
country: Canada
facility: CA037
state: Ontario
city: Beauport
country: Canada
facility: CA005
state: Quebec
city: Greenfield Park
country: Canada
facility: CA023
state: Quebec
city: Montreal
country: Canada
facility: CA013
state: Quebec
city: Sherbrooke
country: Canada
facility: CA031
state: Quebec
city: Sherbrooke
country: Canada
facility: CA012
state: Quebec
city: Vanier
country: Canada
facility: CA030
state: Quebec
city: Verdun
country: Canada
facility: CA017
state: Quebec
city: Regina
country: Canada
facility: CA015
state: Saskatchewan
city: Saskatoon
country: Canada
facility: CA040
state: Saskatchewan
city: Kelowna
country: Canada
facility: CA043
city: Penticton
country: Canada
facility: CA042
Study officials:
affiliation: LundbeckClinicalTrials@lundbeck.com
name: Email contact via H. Lundbeck A/S
role: STUDY_DIRECTOR
References:
citation: Herrmann N, Gauthier S, Boneva N, Lemming OM; 10158 Investigators. A randomized, double-blind, placebo-controlled trial of memantine in a behaviorally enriched sample of patients with moderate-to-severe Alzheimer's disease. Int Psychogeriatr. 2013 Jun;25(6):919-27. doi: 10.1017/S1041610213000239. Epub 2013 Mar 8.