MenopausePhase 2RISENCT00997893
Research Investigation of Soy and Estrogen
A Phase 2 study testing Soy Phytoestrogen, Estradiol and Medroxyprogesterone Acetate (MPA) in people with Menopause and Hot Flashes, run by University of Illinois Chicago at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 65 years, women only
- Conditions the study is for
- Menopause, Hot Flashes
- What is being tested?
- Soy Phytoestrogen, Estradiol and Medroxyprogesterone Acetate (MPA)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 96 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2009to May 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 29Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Illinois at Chicago
Chicago, Illinois, 60612
About this study
Official title: Effects of Estradiol and Soy on Menopausal Symptoms
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.
Read the 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.
- Conditions
- Menopause, Hot Flashes
- Being tested
- Soy Phytoestrogen, Estradiol, Medroxyprogesterone Acetate (MPA), Soy Placebo, MPA Placebo
- Keywords
- menopause, hot flashes, soy, estrogen, anxiety
- Medical subject headings
- Hot Flashes, Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Soy PhytoestrogenDietary supplement
Also called NovaSoy 400
Novasoy® pill (55 mg)
EstradiolDrug
Also called estrogen, estradiol acetate
Estradiol pill (1 mg)
Medroxyprogesterone Acetate (MPA)Drug
Also called MPA
medroxyprogesterone acetate (MPA) (10mg)
Soy PlaceboDrug
Also called sugar pill
oral placebo pill (0mg Soy Phytoestrogen)
MPA PlaceboDrug
Also called sugar pill
oral placebo pill (0mg MPA)
| Study group | Role | What they receive |
|---|---|---|
| Estradiol/Medroxyprogesterone Acetate | Experimental | 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. Receives: Drug: Estradiol; Drug: Medroxyprogesterone Acetate (MPA); Drug: Soy Placebo |
| Soy Phytoestrogen | Experimental | 55 mg/twice daily oral Novasoy®/Soy Phytoestrogen pill for 12 weeks, followed by 0 mg/d oral placebo pill, for 10 days. Receives: Dietary Supplement: Soy Phytoestrogen; Drug: MPA Placebo |
| Placebo | Placebo comparator | 0 mg tablet/twice daily oral placebo pill for 12 weeks, followed by 0 mg/d oral placebo pill, for 10 days. Receives: Drug: Soy Placebo; Drug: MPA Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 0, 10, 12, and 16-18
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.
Measured: Baseline (Week 0) and Treatment (Week 12)
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.
Measured: Baseline (Week 0) and Treatment (Week 12)
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.
Measured: Baseline and 12 weeks
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.
Measured: Baseline and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2009 (estimated)
- Study startDec 2009
- Primary completionMay 2015
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MenopauseStudies of the same condition, open and under way.
- More trials run by University of Illinois ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Illinois Chicago
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Pauline M. Maki, University of Illinois Chicago
- Investigators
- Pauline M Maki, PhD, Principal investigator, University of Illinois Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00997893
- Sponsor's protocol ID
- 2009-0052
- Other IDs
- 5R01MH083782-05
- Acronym
- RISE
- Status last verified
- Nov 2020
- First submitted
- 18 Oct 2009
- Last updated
- 7 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Estradiol and Soy on Menopausal Symptoms
- ClinicalTrials.gov ID
- NCT00997893
- Acronym / sponsor ID
- RISE / 2009-0052
- Conditions
- Menopause, Hot Flashes
- Keywords
- menopause, hot flashes, soy, estrogen, anxiety
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- University of Illinois ChicagoUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Dec 2009 (actual)
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 19 Oct 2009 (estimated)
- Results
- Posted 7 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Estradiol/Medroxyprogesterone Acetate | Experimental | Drug: Estradiol, Drug: Medroxyprogesterone Acetate (MPA), Drug: Soy Placebo1 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. |
| Soy Phytoestrogen | Experimental | Dietary Supplement: Soy Phytoestrogen, Drug: MPA Placebo55 mg/twice daily oral Novasoy®/Soy Phytoestrogen pill for 12 weeks, followed by 0 mg/d oral placebo pill, for 10 days. |
| Placebo | Placebo comparator | Drug: Soy Placebo, Drug: MPA Placebo0 mg tablet/twice daily oral placebo pill for 12 weeks, followed by 0 mg/d oral placebo pill, for 10 days. |
Who may qualify
- Ages
- 40 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (29 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Soy PhytoestrogenAlso: NovaSoy 400Novasoy® pill (55 mg) | Dietary supplement | Soy Phytoestrogen |
| EstradiolAlso: estrogen, estradiol acetateEstradiol pill (1 mg) | Drug | Estradiol/Medroxyprogesterone Acetate |
| Medroxyprogesterone Acetate (MPA)Also: MPAmedroxyprogesterone acetate (MPA) (10mg) | Drug | Estradiol/Medroxyprogesterone Acetate |
| Soy PlaceboAlso: sugar pilloral placebo pill (0mg Soy Phytoestrogen) | Drug | Estradiol/Medroxyprogesterone Acetate, Placebo |
| MPA PlaceboAlso: sugar pilloral placebo pill (0mg MPA) | Drug | Placebo, Soy Phytoestrogen |
Primary outcome
Change in STAI-6 Score
Time frame: Week 0, 10, 12, and 16-18
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
Time frame: Baseline (Week 0) and Treatment (Week 12)
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
Time frame: Baseline (Week 0) and Treatment (Week 12)
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
Time frame: Baseline and 12 weeks
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
Time frame: Baseline and 12 weeks
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- UIC Department of Psychiatry Women's Mental Health Research Program WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Menopause
Recruiting
Hop Extract Versus Soy Isoflavone Extract for Menopausal Symptoms (HOPES)
Menopause, Perimenopause
Not yet recruiting
The Role of Diet Quality in Sleep Among Women in Postmenopause
Post Menopausal Women
Active, not recruitingPhase 3
Human Menopausal Gonadotropin Research in Infertility Assessing Cumulative Live Birth With Frozen Embryo Transfer.
Infertility (IVF Patients)
Not yet recruiting
Effect of Hormone Replacement Therapy on Physiotherapy Outcomes in Postmenopausal Women With Frozen Shoulder
Frozen Shoulder, Adhesive Capsulitis
RecruitingObservational study
Observational Study of Bone Complications in People With Post-menopausal Breast Cancer Who Have Stopped Treatment With Denosumab and Aromatase Inhibitors
Breast Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pauline M Maki, PhD principal investigator
University of Illinois Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Soy Phytoestrogen, Estradiol and Medroxyprogesterone Acetate (MPA) in people with Menopause and Hot Flashes, run by University of Illinois Chicago at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in STAI-6 Score (time frame: Week 0, 10, 12, and 16-18). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2020.