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Research Investigation of Soy and Estrogen (RISE)

Primary Purpose

Menopause, Hot Flashes

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Soy Phytoestrogen
Estradiol
Medroxyprogesterone Acetate (MPA)
Soy Placebo
MPA Placebo
Sponsored by
University of Illinois at Chicago
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Menopause focused on measuring menopause, hot flashes, soy, estrogen, anxiety

Eligibility Criteria

40 Years - 65 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Female
  • Perimenopausal as defined by the Stages of Reproductive Aging Workshop (STRAW) criteria, specifically in either of the two following stages: a) early transition defined as changes in cycle length of seven days or more in either direction in consecutive cycles or b) late transition defined as > 60 days amenorrhea and FSH > 40 IU/mL
  • Intact uterus/ovaries (i.e. no surgical menopause)
  • at least 1 self-reported hot flash per week
  • Estrogen therapy not contraindicated
  • Able to give informed consent
  • Age between 40 and 65 years
  • English as first and primary language

Exclusion Criteria:

  • Positive pregnancy test or breastfeeding (pregnancy tests will be given to all women)
  • Obesity > 35 BMI
  • Previous history of endometrial hyperplasia/neoplasia
  • Previous history of cancers of the breast or reproductive tract
  • History of presence of myocardial infarction (MI) or stroke
  • Current clinical diagnosis or a diagnosis within the past year of an anxiety disorder, severe recurrent depression, or severe psychiatric disturbance
  • History of head injury with more than 60 minutes loss of consciousness
  • History of neurological condition affecting cognitive function (e.g., brain tumor, multiple sclerosis)
  • History of developmental disability affecting cognitive function (e.g., mental retardation, attention deficit)
  • Current use of CNS-acting medication (e.g., antidepressants, anxiolytics, diphenhydramine)
  • History or presence of cerebrovascular accident, sickle cell anemia
  • History of alcohol or drug abuse as defined by DSM criteria
  • Abnormal vaginal bleeding of undetermined cause
  • Untreated or uncontrolled hypertension defined as systolic blood pressure greater than 165 mm hg or diastolic blood pressure greater than 95 mm hg
  • Concurrent administration of medication containing estrogen, progestin, SERM within four months of enrollment
  • Concurrent administration of medication containing St. John's wort, bisphosphonates, or dietary phytoestrogens within one month of enrollment
  • History of migraine associated with hormone use
  • History or presence of deep vein thrombosis, thrombophlebitis or thromboembolic disorder
  • Current participation in any other clinical trial within 30 days of enrollment
  • Smoker
  • Diabetes
  • Premature ovarian failure (defined as having last menstrual period before age 40)
  • Abnormal PAP smear in previous year
  • Abnormal mammogram in previous year
  • Vegans (vegetarians who tend to consume greater than average doses of phytoestrogens)
  • Allergy to soy (affects ~1% of people in the United States; reactions are typically mild)
  • Symptomatic fibroids (significant size or significant menstrual changes)
  • Menorrhagia
  • Lactose intolerant

Sites / Locations

  • University of Illinois at Chicago

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Estradiol/Medroxyprogesterone Acetate

Soy Phytoestrogen

Placebo

Arm Description

1 mg/d oral Estradiol pill and 0 mg/d oral placebo pill for 12 weeks, followed by 10 mg/d oral medroxyprogesterone acetate (MPA) pill, for 10 days.

55 mg/twice daily oral Novasoy®/Soy Phytoestrogen pill for 12 weeks, followed by 0 mg/d oral placebo pill, for 10 days.

0 mg tablet/twice daily oral placebo pill for 12 weeks, followed by 0 mg/d oral placebo pill, for 10 days.

Outcomes

Primary Outcome Measures

Change in STAI-6 Score
STAI-6; State-Trait Anxiety Inventory- Short Form is a measure of anxiety where higher scores indicate higher/elevated anxiety. Minimum value 6 is and maximum value is 24.
Changes in STAI-6 Scores Before and After Psychosocial Stressor Over Time
STAI-6; State-Trait Anxiety Inventory- Short Form is a measure of anxiety where higher scores indicate higher/elevated anxiety. Minimum value 6 is and maximum value is 24.
Memory for Emotionally Valent Words and Neutral Words
Proportion correct out of 18 word pairs (6 positive, 6 negative and 6 neutral) after laboratory-induced stress using Trier Social Stress Test (TSST). Maximum score is 18 and minimum score is 0; higher scores indicate a better score.
Change in Verbal Memory, Immediate Recall
Immediate recall on the Logical Memory subset of the Wechsler Memory Scale-Revised, in which higher scores indicate a better recall and outcome. The minimum value is 0 and maximum value is 25.
Change in Verbal Memory, Delayed Recall
Delayed recall on the Logical Memory subset of the Wechsler Memory Scale-Revised, in which higher scores indicate a better recall and outcome. The minimum value is 0 and maximum value is 25.

Secondary Outcome Measures

Full Information

First Posted
October 18, 2009
Last Updated
November 12, 2020
Sponsor
University of Illinois at Chicago
Collaborators
National Institute of Mental Health (NIMH)
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1. Study Identification

Unique Protocol Identification Number
NCT00997893
Brief Title
Research Investigation of Soy and Estrogen
Acronym
RISE
Official Title
Effects of Estradiol and Soy on Menopausal Symptoms
Study Type
Interventional

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
December 2009 (Actual)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
May 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Illinois at Chicago
Collaborators
National Institute of Mental Health (NIMH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine the effects of oral estradiol and soy phytoestrogens on anxiety, stress responsivity and cognition in perimenopausal women.
Detailed Description
Anxiety is a common, but understudied complaint in midlife women, and increases during the menopausal transition. Changes in estrogen are dramatic during the menopausal transition, and indirect data suggest a potential role for estrogen, particularly estrogen receptor beta, in mediating anxiety. Two subtypes of the estrogen receptor, alpha and beta (ER-alpha and ER-beta), appear to be critically involved in the expression of anxiety in females. Compounds that preferentially target ER-beta, including plant-derived estrogens (phytoestrogens), lower both anxiety behaviors and responsivity to discrete stressors, including social stress, in laboratory animals. The primary aim of this proposal is to carry out the first study to translate these preclinical studies to humans by comparing and contrasting of the effects of phytoestrogens, estradiol, and placebo on daily anxiety and responses to moderate psychosocial stress in the laboratory. As second focus is emotional and non-emotional cognition. This focus stems from evidence that estrogen can protect against the negative impact of glucocorticoids on memory. These aims will be accomplished in a 12-week randomized placebo-controlled, clinical trial comparing three treatments: 1) a phytoestrogen supplement (Novasoy® 400, 55 mg tablet twice daily); 2) oral estradiol (1 mg/daily; plus 10 mg medroxyprogesterone acetate at study end 10 for 10 days); and 3) placebo (identical appearing tablets twice daily). The enrollment target is 120 healthy women in the menopausal transition (40 per group). To measure anxiety, women will complete the State-Trait Anxiety Inventory (STAI). To measure responsivity to psychosocial stress, parallel forms of the Trier Social Stress Test, a widely used laboratory induction that involves unanticipated public speaking and social evaluative fear, will be used to induce moderate psychosocial stress before and after treatment. At both laboratory sessions, measures of subjective stress (STAI), cortisol, and emotional memory performance will be obtained at multiple points during a control condition and during the psychosocial stress condition. Lastly, we will measure treatment effects on measures of verbal memory.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Menopause, Hot Flashes
Keywords
menopause, hot flashes, soy, estrogen, anxiety

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
96 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Estradiol/Medroxyprogesterone Acetate
Arm Type
Experimental
Arm Description
1 mg/d oral Estradiol pill and 0 mg/d oral placebo pill for 12 weeks, followed by 10 mg/d oral medroxyprogesterone acetate (MPA) pill, for 10 days.
Arm Title
Soy Phytoestrogen
Arm Type
Experimental
Arm Description
55 mg/twice daily oral Novasoy®/Soy Phytoestrogen pill for 12 weeks, followed by 0 mg/d oral placebo pill, for 10 days.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
0 mg tablet/twice daily oral placebo pill for 12 weeks, followed by 0 mg/d oral placebo pill, for 10 days.
Intervention Type
Dietary Supplement
Intervention Name(s)
Soy Phytoestrogen
Other Intervention Name(s)
NovaSoy 400
Intervention Description
Novasoy® pill (55 mg)
Intervention Type
Drug
Intervention Name(s)
Estradiol
Other Intervention Name(s)
estrogen, estradiol acetate
Intervention Description
Estradiol pill (1 mg)
Intervention Type
Drug
Intervention Name(s)
Medroxyprogesterone Acetate (MPA)
Other Intervention Name(s)
MPA
Intervention Description
medroxyprogesterone acetate (MPA) (10mg)
Intervention Type
Drug
Intervention Name(s)
Soy Placebo
Other Intervention Name(s)
sugar pill
Intervention Description
oral placebo pill (0mg Soy Phytoestrogen)
Intervention Type
Drug
Intervention Name(s)
MPA Placebo
Other Intervention Name(s)
sugar pill
Intervention Description
oral placebo pill (0mg MPA)
Primary Outcome Measure Information:
Title
Change in STAI-6 Score
Description
STAI-6; State-Trait Anxiety Inventory- Short Form is a measure of anxiety where higher scores indicate higher/elevated anxiety. Minimum value 6 is and maximum value is 24.
Time Frame
Week 0, 10, 12, and 16-18
Title
Changes in STAI-6 Scores Before and After Psychosocial Stressor Over Time
Description
STAI-6; State-Trait Anxiety Inventory- Short Form is a measure of anxiety where higher scores indicate higher/elevated anxiety. Minimum value 6 is and maximum value is 24.
Time Frame
Baseline (Week 0) and Treatment (Week 12)
Title
Memory for Emotionally Valent Words and Neutral Words
Description
Proportion correct out of 18 word pairs (6 positive, 6 negative and 6 neutral) after laboratory-induced stress using Trier Social Stress Test (TSST). Maximum score is 18 and minimum score is 0; higher scores indicate a better score.
Time Frame
Baseline (Week 0) and Treatment (Week 12)
Title
Change in Verbal Memory, Immediate Recall
Description
Immediate recall on the Logical Memory subset of the Wechsler Memory Scale-Revised, in which higher scores indicate a better recall and outcome. The minimum value is 0 and maximum value is 25.
Time Frame
Baseline and 12 weeks
Title
Change in Verbal Memory, Delayed Recall
Description
Delayed recall on the Logical Memory subset of the Wechsler Memory Scale-Revised, in which higher scores indicate a better recall and outcome. The minimum value is 0 and maximum value is 25.
Time Frame
Baseline and 12 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Female Perimenopausal as defined by the Stages of Reproductive Aging Workshop (STRAW) criteria, specifically in either of the two following stages: a) early transition defined as changes in cycle length of seven days or more in either direction in consecutive cycles or b) late transition defined as > 60 days amenorrhea and FSH > 40 IU/mL Intact uterus/ovaries (i.e. no surgical menopause) at least 1 self-reported hot flash per week Estrogen therapy not contraindicated Able to give informed consent Age between 40 and 65 years English as first and primary language Exclusion Criteria: Positive pregnancy test or breastfeeding (pregnancy tests will be given to all women) Obesity > 35 BMI Previous history of endometrial hyperplasia/neoplasia Previous history of cancers of the breast or reproductive tract History of presence of myocardial infarction (MI) or stroke Current clinical diagnosis or a diagnosis within the past year of an anxiety disorder, severe recurrent depression, or severe psychiatric disturbance History of head injury with more than 60 minutes loss of consciousness History of neurological condition affecting cognitive function (e.g., brain tumor, multiple sclerosis) History of developmental disability affecting cognitive function (e.g., mental retardation, attention deficit) Current use of CNS-acting medication (e.g., antidepressants, anxiolytics, diphenhydramine) History or presence of cerebrovascular accident, sickle cell anemia History of alcohol or drug abuse as defined by DSM criteria Abnormal vaginal bleeding of undetermined cause Untreated or uncontrolled hypertension defined as systolic blood pressure greater than 165 mm hg or diastolic blood pressure greater than 95 mm hg Concurrent administration of medication containing estrogen, progestin, SERM within four months of enrollment Concurrent administration of medication containing St. John's wort, bisphosphonates, or dietary phytoestrogens within one month of enrollment History of migraine associated with hormone use History or presence of deep vein thrombosis, thrombophlebitis or thromboembolic disorder Current participation in any other clinical trial within 30 days of enrollment Smoker Diabetes Premature ovarian failure (defined as having last menstrual period before age 40) Abnormal PAP smear in previous year Abnormal mammogram in previous year Vegans (vegetarians who tend to consume greater than average doses of phytoestrogens) Allergy to soy (affects ~1% of people in the United States; reactions are typically mild) Symptomatic fibroids (significant size or significant menstrual changes) Menorrhagia Lactose intolerant
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pauline M Maki, PhD
Organizational Affiliation
University of Illinois at Chicago
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Illinois at Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://www.psych.uic.edu/research/womens-mental-health-research-program
Description
UIC Department of Psychiatry Women's Mental Health Research Program Website

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Research Investigation of Soy and Estrogen

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