Cognition in the Study of Tamoxifen and Raloxifene

Study Overview
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Brief Summary
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The purpose of this study is to assess the effects of tamoxifen and raloxifene on cognitive aging in selected cognitively-healthy women.

Detailed Description
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Recent reports indicate that hormone therapy (HT) may have a protective effect on the aging brain. Although previous studies have examined the effects of HT on age-related cognitive changes, there is little information on the effect of a new class of estrogenic agents, selective estrogen receptor modulators (SERMs), on cognitive aging. The two most commonly prescribed SERMs are tamoxifen, for treatment and prevention of breast cancer, and raloxifene, for maintaining bone density. In the face of potential widespread use of SERMs in healthy women, information on the effects of these agents on memory and other cognitive functions is essential. The principal goals of Co-STAR are to compare the effects of tamoxifen and raloxifene on age-associated declines in measures of verbal and nonverbal memory in women over age 65 other cognitive abilities and mood with those resulting from more common forms of HT, specifically ET (conjugated equine estrogen) and ET plus progesterone Co-STAR results will be compared to results from the Women's Health Initiative Study of Cognitive Aging (WHISCA), a study involving 6-year longitudinal assessment of cognitive outcomes in 2969 women randomly assigned to receive active treatment (Premarin or Premarin plus medroxyprogesterone acetate) or placebo. A comparison of the Co-STAR treatment groups with the group of WHISCA participants receiving placebo will provide insights into the effects of SERMs relative to no treatment. A comparison of the Co-STAR treatment groups with WHISCA treatment groups receiving ET or ET plus progesterone will provide insights into the effects of SERMs relative to common HT treatments. Co-STAR participants will be recruited from The National Cancer Institute's (NCI) Study of Tamoxifen and Raloxifene (STAR) NCT00003906, a multi-center, 5-year, randomized clinical trial among 22,000 women at increased risk for breast cancer, to compare the effects of tamoxifen and raloxifene on risk for breast cancer.

Official Title
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Effects of Selective Estrogen Receptor Modulators on Cognitive Aging: Cognition in the Study of Tamoxifen and Raloxifene

Conditions
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Cognition, Aging

Intervention / Treatment
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* Drug: tamoxifen
* Drug: raloxifene


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women enrolled in STAR trial at a site participating in Co-STAR 65 years of age or older Have been randomized into STAR but have not started taking the study drug OR enrolled in STAR for a minimum of one year Have not been diagnosed with dementia Have signed a separate consent document for the Co-STAR Study Previous diagnoses of chronic neurologic disease (Parkinson's disease, stroke, epilepsy, multiple sclerosis), history of head injury, depression, alcohol addiction, drug addiction, and other neurologic or psychiatric conditions will be recorded but will not serve as exclusion factors for this study Exclusion Criteria: Not enrolled in the STAR Trial Younger than 65 years of age Diagnosed with dementia

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Star participants assigned to Tamoxifen<br>Participants in the parent study, STAR assigned to Tamoxifen who were 65 or older at time of enrollment. | Drug: tamoxifen<br>* oral tamoxifen plus placebo daily for 5 years<br>* Other names: Nolvadex;|
| Experimental: Star participants assigned to Raloxifene<br>Participants in the parent study, STAR assigned to Raloxifene who were 65 or older at time of enrollment. | Drug: raloxifene<br>* oral raloxifene plus placebo daily for 5 years<br>* Other names: Evista, Keoxifene;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline on the the Benton Visual Retention Test Scores by Treatment Group | Mean Change From Baseline on the Benton Visual Retention (BVRT) Test scores. Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. The BVRT measures short term visual memory and visuo-constructional abilities. Each of 10 designs was presented one at a time for 10 seconds, and immediately after the design was withdrawn, the participant was instructed to draw it from memory on a blank sheet of paper. The score on the BVRT is the total number of errors, 0-26 represents the total number of theoretically possible errors. Lower score denotes better outcomes. | Baseline and 3 Years | 
| Mean Change From Baseline on the the California Verbal Learning Test Scores by Treatment Group | Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. The experimenter reads a list of 16 nouns aloud, at one-second intervals, in fixed order, over 3 learning trials (list A) . After each trial, the subject is asked to recall as many words as they can in any order (i.e., free recall) given a score 0-16 each. Total range as the sum of the 3 learning trials: 0 - 48. Participants were asked to recall a second interference list (List B) with a score range of 0-16. Free recall of list A are tested immediately after list B (short-delay) Total range 0- 16 , and again after 20 minutes (long-delay) 0-16. Each part of the scale is reported separately as Total List A trials, Total List B trials, Short-delay free recall, and Long-delay free recall. | Baseline and 3 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline on the Letter Fluency and Semantic Fluency Scores by Treatment Group | Mean Change From Baseline on the Letter Fluency Test scores. Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. Measures cognitive function. In this test, the participant names as many words as possible in 1 minute, beginning with each letter for letter fluency (F, A, and S) and category for semantic fluency (fruits and vegetables). To score the administrator, counts up the total number letters or words that the individual is able to produce. The score minimum would be 0 and the maximum would be the total of correct items named within 1 minute. Higher scores represent better outcomes. | Baseline and 3 Years | 
| Mean Change From Baseline on Digit Span Test Scores by Treatment Group | Mean Change From Baseline on the Digit Span Test - Digits Forward and Digits backward Test scores. Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. Measures reasoning, verbal ability, and memory. The participant is asked to provide immediate recall of a series of digits in forward and backward sequences. The individual's score is the total number of items correctly repeated forwards or backwards. Total range 0 - 14, higher results denotes a better outcome. | Baseline and 3 Years | 
| Mean Change From Baseline on Card Rotations Test Scores by Treatment Group | Mean Change From Baseline on the Card Rotations Test scores. Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. Measures the ability to mentally manipulate figures in two and three-dimensions. On each of 28 trials, participants view sample line drawings of a geometric figure and 8 alterations representing 2 or 3-dimensional rotations of the drawing. Participants are asked to identify alternatives that show the sample in 2-D but not in 3-D. Total range 0 - 160 and the number of incorrect/correct responses is measure. Higher number of correct answers is a better outcome. | Baseline and 3 Years | 
| Mean Change From Baseline on the Finger Tapping Test Scores by Treatment Group | Mean Change From Baseline on the the Finger Tapping Test scores. Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. Measures motor speed, coordination, attention, alertness, slowing of responses, and motor control. In this test of motor speed and dexterity participants are asked to depress a lever as many times as possible in each of 7, 10-second trials, first with the right hand and next with the left hand. The highest and lowest scores are dropped; the score is the average of the remaining five trials for each hand.Higher scores represent better outcomes. | Baseline and 3 Years | 
| Mean Change From Baseline on the Positive and Negative Affect Schedule Scores by Treatment Group | Mean Change From Baseline on the Positive and Negative Affect Schedule (PANAS). Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. Measures positive and negative affect. Mood is assessed with the PANAS, a list of ten pleasant mood states (e.g., interested, proud, inspired) and ten unpleasant mood states (e.g., irritable, guilty, jittery). Respondents are asked to rate on a 5-point scale (1 being very slightly or not at all and 5 being extremely) the extent to which they have experienced each mood during a specific time frame. Ratings for each item can range from 0 to 4 with total scores for positive affect and negative affect subscales ranging from 0 to 40. For positive affect, higher scores denote higher levels of positive affect and for negative affect, lower scores denote lower levels of negative affect. | Baseline and 3 Years | 
| Mean Change From Baseline on the Geriatric Depression Scale Scores by Treatment Group | Mean Change From Baseline on the Geriatric Depression Scale. Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. Measures depression in older adults. Mood is also assessed with the 15-item short form of the GDS which measures non-somatic features of depressed mood. Participants indicate the presence or absence of each symptom. The GDS-SF score is the total number of positive depressive items. Score range is 0-15, with 0-4 denoting better outcomes and a score of 5 and above denoting worse outcomes (depression). | Baseline and 3 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, Tamoxifen, Raloxifene, hormone therapy