Cognition in the Study of Tamoxifen and Raloxifene

Aging Clinical Trial

— Co-STAR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00687102
• Other study ID #: IA0132
• Secondary ID: 1R13AG020218-01
• Status: Completed
• Phase: Phase 3
• Start date: October 2001
• Est. completion date: March 2008

Study information

• Verified date: August 2018
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Other known NCT identifiers

• NCT00571857

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1498
• Est. completion date: March 2008
• Est. primary completion date: March 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 65 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aging
• Cognition

Intervention

Drug:
• tamoxifen
oral tamoxifen plus placebo daily for 5 years
• raloxifene
oral raloxifene plus placebo daily for 5 years

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Women's Breast Health Centre	Ottawa	Ontario
Canada	Thunder Bay Regional Health Sciences Centre, Regional Cancer Care Clinical Trials	Thunder Bay	Ontario
Canada	North York General Hospital	Toronto	Ontario
Canada	Women's College Hospital	Toronto	Ontario
Canada	UBC-Vancouver Hospital & Health Science Center	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnepeg	Manitoba
United States	Don and Sybil Harrington Cancer Center	Amarillo	Texas
United States	Genesys Hurley Cancer Institute	Ann Arbor	Michigan
United States	Genesys Regional Medical Center	Ann Arbor	Michigan
United States	Oakwood Healthcare System	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	St. John Hospital and Medical Center	Ann Arbor	Michigan
United States	The Harry and Jeanette Weinberg Cancer Institute at Franklin Square	Baltimore	Maryland
United States	Battle Creek Health Systems	Battle Creek	Michigan
United States	Kaiser Permanente Ohio	Bedford	Ohio
United States	Montana Cancer Consortium	Billings	Montana
United States	Boston Medical Center	Boston	Massachusetts
United States	Olympic Hematology and Oncology Associates	Bremerton	Washington
United States	Roswell Park/Western New York STAR Consortium	Buffalo	New York
United States	Naval Hospital Camp Pendleton	Camp Pendleton	California
United States	Roper Hospital	Charleston	South Carolina
United States	Blumenthal Cancer Center	Charlotte	North Carolina
United States	Presbyterian Hospital	Charlotte	North Carolina
United States	Rush-Presbyterian-St. Luke's Medical Center	Chicago	Illinois
United States	Ireland Cancer Center at Case Western Reserve University	Cleveland	Ohio
United States	Penrose Cancer Center	Colorado Springs	Colorado
United States	Ellis Fischel Cancer Center	Columbia	Missouri
United States	Palmetto Richland Memorial Hospital	Columbia	South Carolina
United States	CCOP Columbus	Columbus	Ohio
United States	Bassett Healthcare	Cooperstown	New York
United States	Baylor-Sammons Cancer Center	Dallas	Texas
United States	Methodist Hospitals of Dallas	Dallas	Texas
United States	Presbyterian Hospital of Dallas	Dallas	Texas
United States	UT Southwestern Center for Breast Care	Dallas	Texas
United States	Danville Hematology & Oncology, Inc.	Danville	Virginia
United States	Genesis Medical Center	Davenport	Iowa
United States	Colorado Cancer Research Program	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	City of Hope National Medical Center	Duarte	California
United States	Hematology Oncology Consultants	Duarte	California
United States	Southern Nevada Cancer Research Foundation	Duarte	California
United States	Finely Hospital, Wendt Regional Cancer Center	Dubuque	Iowa
United States	Duluth Clinic	Duluth	Minnesota
United States	St. Luke's Hospital	Duluth	Minnesota
United States	Duke University Medical Center	Durham	North Carolina
United States	Hematology-Oncology Associates of CNY	East Syracuse	New York
United States	Cape Fear Valley Medical Center	Fayetteville	North Carolina
United States	McLaren Regional Medical Center	Flint	Michigan
United States	Virginia K. Crosson Cancer Center	Fullerton	California
United States	Baylor Medical Center at Garland	Garland	Texas
United States	Gaston Memorial Hospital	Gastonia	North Carolina
United States	Glendale Memorial Hospital Comprehensive Cancer Center	Glendale	California
United States	Southeastern Medical Oncology Center	Goldsboro	North Carolina
United States	Center for Cancer Care at Goshen Health Systems	Goshen	Indiana
United States	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan
United States	Great Falls Clinic, LLP	Great Falls	Montana
United States	Cancer Centers of the Carolinas	Greenville	South Carolina
United States	East Carolina University	Greenville	North Carolina
United States	Hartford Hospital	Hartford	Connecticut
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	University of Hawaii, Honolulu	Honolulu	Hawaii
United States	Breast Care Center at Baylor College of Medicine/Methodist Hospital	Houston	Texas
United States	University of Texas M. D. Anderson Cancer Center	Houston	Texas
United States	St John's Regional Medical Center Cancer Center	Joplin	Missouri
United States	Kalamazoo	Kalamazoo	Michigan
United States	Good Samaritan Health Systems	Kearney	Nebraska
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	Wilford Hall Medical Center	Lackland Air Force Base	Texas
United States	Lakeland Regional Cancer Center	Lakeland	Florida
United States	Valley Tumor Medical Group	Lancaster	California
United States	Michigan State University	Lansing	Michigan
United States	Lima Memorial Hospital	Lima	Ohio
United States	Cancer Resource Center	Lincoln	Nebraska
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	Southwest Cancer Center	Lubbock	Texas
United States	Marquette General Hospital	Marquette	Michigan
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Hennepin Consortium	Minneapolis	Minnesota
United States	Mercy Memorial Hospital Cancer Center	Monroe	Michigan
United States	Community Hospital	Munster	Indiana
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Lawrence & Memorial Hospital	New London	Connecticut
United States	Ochsner Cancer Institute	New Orleans	Louisiana
United States	Christiana Care Health Services	Newark	Delaware
United States	Kaiser Permanente Division of Research	Oakland	California
United States	Methodist Cancer Center, Omaha	Omaha	Nebraska
United States	Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Ventura County Hematology-Oncology Specialists	Oxnard	California
United States	CCOP Western Regional	Phoenix	Arizona
United States	UPMC/UPCI/Magee Women's Hospital	Pittsburgh	Pennsylvania
United States	Berkshire Hematology Oncology, P.C.	Pittsfield	Massachusetts
United States	Baylor Regional Medical Center	Plano	Texas
United States	Columbia River Oncology Program	Portland	Oregon
United States	Kaiser Permanente Center for Health Research (Oncology Research)	Portland	Oregon
United States	Vassar Brothers Hospital	Poughkeepsie	New York
United States	St. Mary-Corwin Medical Center	Pueblo	Colorado
United States	Riverview Medical Center	Red Bank	New Jersey
United States	North Valley Breast Clinic	Redding	California
United States	University of Rochester Cancer Center	Rochester	New York
United States	SwedishAmerican Hospital Regional Cancer Ctr	Rockford	Illinois
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	Alvin J Siteman Cancer Center at Barnes-Jewish Hosp & Washington U Sch of Med	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Metro-Minnesota	Saint Louis Park	Minnesota
United States	Huntsman Cancer Institute at the University of Utah	Salt Lake City	Utah
United States	Kaiser Permanente Oncology Research	San Diego	California
United States	Naval Medical Center San Diego	San Diego	California
United States	Cancer Foundation of Santa Barbara	Santa Barbara	California
United States	Memorial Medical Center	Savannah	Georgia
United States	Mercy Cancer Center, Scranton	Scranton	Pennsylvania
United States	Benaroya Research Institute at Virginia Mason	Seattle	Washington
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Swedish Medical Center	Seattle	Washington
United States	Sioux Valley Clinic Oncology	Sioux Falls	South Dakota
United States	CCOP,Northern Indiana Research Consortium	South Bend	Indiana
United States	Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Cancer Research for the Ozarks	Springfield	Missouri
United States	St John's Health System	Springfield	Missouri
United States	University Healthcare System	Syracuse	New York
United States	H. Lee Moffitt Cancer Center and Research Center	Tampa	Florida
United States	Scott and White Hospital	Temple	Texas
United States	Fulton County Health Center	Toledo	Ohio
United States	Toledo Community Hospital Oncology Program	Toledo	Ohio
United States	Arizona Cancer Center	Tucson	Arizona
United States	Hematology & Oncology Associates Ltd	Tupelo	Mississippi
United States	Carle Cancer Center	Urbana	Illinois
United States	Washington Cancer Institute	Washington	District of Columbia
United States	Via Christi Regional Medical Center	Wichita	Kansas
United States	Forsyth Regional Cancer Center	Winston-Salem	North Carolina
United States	Wake Forest University School of Medicine	Winston-Salem	North Carolina
United States	Kaiser Permanente, Woodland Hills	Woodland Hills	California
United States	Yakima Valley Memorial Hospital/North Star Lodge Cancer Center	Yakima	Washington
United States	York Cancer Center	York	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Wake Forest University	National Institute on Aging (NIA)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (3)

Maki PM, Zonderman AB, Resnick SM. Enhanced verbal memory in nondemented elderly women receiving hormone-replacement therapy. Am J Psychiatry. 2001 Feb;158(2):227-33. — View Citation

Resnick SM, Maki PM, Golski S, Kraut MA, Zonderman AB. Effects of estrogen replacement therapy on PET cerebral blood flow and neuropsychological performance. Horm Behav. 1998 Oct;34(2):171-82. — View Citation

Resnick SM, Metter EJ, Zonderman AB. Estrogen replacement therapy and longitudinal decline in visual memory. A possible protective effect? Neurology. 1997 Dec;49(6):1491-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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