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Treatment With Namenda in Women at Risk for Cognitive Decline

Cognitive Effects of Memantine in Postmenopausal Women at Risk of Dementia: a Pilot Study

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00242632
Enrollment
22
Registered
2005-10-20
Start date
2004-06-30
Completion date
2009-12-31
Last updated
2017-06-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Dementia

Brief summary

This research aims to explore the effectiveness of memantine (Namenda) in treating post-menopausal women between the ages of 50 and 65, who are at risk for cognitive decline. Memantine has already been shown to offer cognitive benefits to patients suffering from Alzheimer's disease, but it's potential for treating those at risk for cognitive decline without Alzheimer's disease or other dementia has yet to be evaluated. It is possible that memantine may offer neurocognitive benefits to this population, as well. Participants are asked to take medication for six months, complete neuropsychological testing, and one blood draw.

Detailed description

Memantine is a well-tolerated moderate-affinity, uncompetitive, voltage-dependent NMDA receptor antagonist that is shown to improve cognition and behavior in mild to moderate and moderate to severe Alzheimer's disease (AD). More recent, albeit limited, evidence also shows benefits of memantine treatment in a host of other disorders such as vascular dementia, pervasive developmental disorders, depression and frontal temporal dementia case studies. However, no studies to date have sought to determine if memantine has potential as a primary prevention for AD. Incidence rates of AD are expected to more than double from 1995 to the year 2050 as baby boomers age and it is predicted that this substantial increase will create a devastating global burden. At present, there are no treatments that prevent or 'cure' AD; however, treatments that delay the onset of dementia could provide significant reductions in incident rates. Epidemiological studies estimate that an increase in cognitive reserve of only 5% would substantially reduce the incidence rate of AD by one-third; therefore, interventions that precede the manifestation of AD would be most beneficial. Over the past several years, research on dementia focused on determining the factors that were involved in the progression from mild cognitive impairment to dementia. Clearly, when interventions can be introduced before any cognitive decline is evident the better the chance of reducing incidence dementia. Few studies have investigated risk factors for AD other than genetic vulnerability and primary prevention studies are essentially non-existent. Known and putative risk factors for AD include being a carrier of an apolipoprotein E-epsilon 4 (apoE-ɛ4) allele, particularly for late-onset AD, family history of AD, history of depression, hypothyroidism, and diabetes. This study was a prospective open-label, 6-month pilot medication trial to determine potential salutary effects of memantine on cognition in women at risk of AD. The study design included built-in control for the genetic risk factor for AD (apoE-ɛ4 status). In addition, this study sought to determine whether memantine administration could provide any cognitive benefits to a population of normal postmenopausal women with at least one other putative risk factor for AD.

Interventions

Namenda has already been shown to offer cognitive benefits to patients suffering from Alzheimer's disease, but it's potential for treating those at risk for cognitive decline without Alzheimer's disease or other dementia has yet to be evaluated. It is possible that memantine may offer neurocognitive benefits to this population, as well. Participants are asked to take medication for six months, complete neuropsychological testing, and one blood draw.

Sponsors

Forest Laboratories
CollaboratorINDUSTRY
Stanford University
Lead SponsorOTHER

Study design

Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
FEMALE
Age
50 Years to 65 Years
Healthy volunteers
Yes

Inclusion criteria

: * Women between the ages of 50-65 * Willing to sign Human Subjects Protection Consent Form * Personal or family history of mood disorder * Hypothyroidism * Diabetes * Family history of Alzheimer's disease

Exclusion criteria

- Possible or probable Alzheimer's disease or dementia * History of cerebrovascular disease * History of myocardial infarction within the previous year * History of unstable heart disease * Uncontrolled hypertension * Less than 8 years of education * English as a 2nd language * Uncorrected vision or hearing deficits

Design outcomes

Primary

MeasureTime frameDescription
Change in California Verbal Learning Test - Second Edition Proactive Interference Test Between Time 1 and Time 26 monthsThis tests verbal memory (word list). A list of words is presented and subjects are asked to recall as many as they can. Then a list of interference words is presented. Finally a recognition list of 44 words is presented where subjects are asked to distinguish between target words and distractors. The mean difference in the percentage of target words recalled between time 1 and time 2 is calculated below.

Secondary

MeasureTime frameDescription
Change in Delis-Kaplan Executive Function System (DKEFS) Verbal Fluency Category Switching Between Time 1 and Time 26 monthsThe Delis-Kaplan Executive Function System (DKEFS) Verbal Fluency Category Switching test measures letter fluency, category fluency, and category switching. The score is the total number of correct words generated during each of the 60-second trials within the three conditions of the test. The mean difference in the total number of correct words generated between time 1 and time 2 is calculated below.

Countries

United States

Participant flow

Participants by arm

ArmCount
apoE-e4-
Subjects without the apoE-e4 allele
11
apoE-e4+
Subjects with the apoE-e4 allele
11
Total22

Baseline characteristics

CharacteristicapoE-e4+apoE-e4-Total
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
11 Participants11 Participants22 Participants
Age, Continuous59.09 years
STANDARD_DEVIATION 0
57.73 years
STANDARD_DEVIATION 0
58.41 years
STANDARD_DEVIATION 0
Region of Enrollment
United States
11 participants11 participants22 participants
Sex: Female, Male
Female
11 Participants11 Participants22 Participants
Sex: Female, Male
Male
0 Participants0 Participants0 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 110 / 11
other
Total, other adverse events
0 / 110 / 11
serious
Total, serious adverse events
0 / 110 / 11

Outcome results

Primary

Change in California Verbal Learning Test - Second Edition Proactive Interference Test Between Time 1 and Time 2

This tests verbal memory (word list). A list of words is presented and subjects are asked to recall as many as they can. Then a list of interference words is presented. Finally a recognition list of 44 words is presented where subjects are asked to distinguish between target words and distractors. The mean difference in the percentage of target words recalled between time 1 and time 2 is calculated below.

Time frame: 6 months

Population: All participants were grouped together for this Outcome Measure. As per the protocol, the analyses of neuropsychological variables were to be done separately for the ApoE-ɛ4 carriers and non-carriers, only if the ApoE-ε4 status was a significant predictor of change in neuropsychological performance.

ArmMeasureValue (MEAN)Dispersion
T1-T2Change in California Verbal Learning Test - Second Edition Proactive Interference Test Between Time 1 and Time 220.41 percentage of target words recalledStandard Deviation 5.63
Secondary

Change in Delis-Kaplan Executive Function System (DKEFS) Verbal Fluency Category Switching Between Time 1 and Time 2

The Delis-Kaplan Executive Function System (DKEFS) Verbal Fluency Category Switching test measures letter fluency, category fluency, and category switching. The score is the total number of correct words generated during each of the 60-second trials within the three conditions of the test. The mean difference in the total number of correct words generated between time 1 and time 2 is calculated below.

Time frame: 6 months

Population: All participants were grouped together for this Outcome Measure. As per the protocol, the analyses of neuropsychological variables were to be done separately for the ApoE-ɛ4 carriers and non-carriers, only if the ApoE-ε4 status was a significant predictor of change in neuropsychological performance.

ArmMeasureValue (MEAN)Dispersion
T1-T2Change in Delis-Kaplan Executive Function System (DKEFS) Verbal Fluency Category Switching Between Time 1 and Time 21.11 correct wordsStandard Deviation 0.23

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026