MsFLASH-03: Comparative Efficacy of Low-Dose Estradiol and Venlafaxine XR for Treatment of Menopausal Symptoms
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ClinicalTrials.gov Identifier: NCT01418209 |
Recruitment Status
:
Completed
First Posted
: August 17, 2011
Results First Posted
: August 20, 2014
Last Update Posted
: August 27, 2014
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Condition or disease | Intervention/treatment | Phase |
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Hot Flashes Menopause Vasomotor Disturbance | Drug: Low-dose 17-ß-estradiol with progesterone taper Drug: Venlafaxine XR Drug: Placebo | Not Applicable |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 339 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | MsFLASH-03: Comparative Efficacy of Low-Dose Estradiol and the SNRI Venlafaxine XR for Treatment of Menopausal Symptoms |
Study Start Date : | November 2011 |
Actual Primary Completion Date : | January 2013 |
Actual Study Completion Date : | January 2013 |

Arm | Intervention/treatment |
---|---|
Active Comparator: Low-dose 17-ß-estradiol with progesterone taper |
Drug: Low-dose 17-ß-estradiol with progesterone taper
Low-dose 17-ß-estradiol oral (by mouth), 0.5 mg once per day for 8 (eight) weeks. 17-ß-estradiol is approved by the US Food and Drug Administration (FDA) and is indicated for the treatment of menopausal symptoms. ß is the Greek symbol for beta; the symbol and the word are used interchangeably. The 8 week estradiol treatment is followed by 14 days (2 weeks) of progesterone taper (as medroxy-progesterone 10 mg/day).
Other Name: The brand name of estradiol being used in this study is Estrace®.
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Active Comparator: Venlafaxine XR |
Drug: Venlafaxine XR
Venlafaxine oral (by mouth) 37.5 mg once per day for 1 (one) week, then 75 mg once per day for 7 (seven) weeks. Venlafaxine XR should not be taken while also taking monoamine oxidase inhibitors (MAOIs). Venlafaxine XR is approved by the US Food and Drug Administration (FDA) for treatment of depression, generalized anxiety disorder, social anxiety disorder, and panic disorder, and is available by prescription. Venlafaxine XR is not FDA-approved for the treatment of hot flashes, although prior studies have indicated that it is useful for treating hot flashes and vasomotor symptoms. After the 8-week venlafaxine XR study treatment period, women will receive a tapering dose of venlafaxine XR 37.5 mg once per day for 14 days (2 weeks).
Other Name: The brand name of venlafaxine XR that is being used in this study is Effexor XR®
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Placebo Comparator: Placebo |
Drug: Placebo
The placebo is an inactive pill that looks like the active medication.
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- Frequency of Hot Flashes (Vasomotor Symptom [VMS] Frequency) -- Week 4 [ Time Frame: Week 4 ]Measured by self-report diary twice daily (day and night). The day and night frequencies were summed to produce a single number of hot flashes per day. The single number of hot flashes per day were summed and averaged for one week prior to the week 4 study assessment to produce a mean daily frequency for week 4.
- Frequency of Hot Flashes (Daily Vasomotor Symptom [VMS] Frequency) -- Week 8 [ Time Frame: Week 8 ]Measured by self-report diary twice daily (day and night). The day and night frequencies were summed to produce a single number of hot flashes per day. The single number of hot flashes per day were summed and averaged for one week prior to the week 8 study assessment to produce a mean daily frequency for week 8.
- Severity of Hot Flashes -- Week 4 [ Time Frame: Week 4 ]Measured by self-report diary twice daily (day and night) for 7 days. Severity ratings ranged from 0 to 3 with lower numbers being less severe and higher numbers being more severe. Data from the day and night severity ratings were averaged for a single daily score. The single daily scores for the week prior to the week 4 study assessment were summed and averaged to produce a mean daily VMS severity for week 4.
- Severity of Hot Flashes -- Week 8 [ Time Frame: Week 8 ]Measured by self-report diary twice daily (day and night) for 7 days. Severity ratings ranged from 0 to 3 with lower numbers being less severe and higher numbers being more severe. Data from the day and night severity ratings were averaged for a single daily score. The single daily scores for the week prior to the week 8 study assessment were summed and averaged to produce a mean daily VMS severity for week 8.
- Bothersomeness of Hot Flashes -- Week 4 [ Time Frame: Week 4 ]Measured by self-report diary twice daily (day and night) for 7 days. Bothersomeness ratings ranged from 0 to 3 with lower numbers being less bothersome and higher numbers being more bothersome. Data from the day and night bothersomeness ratings were averaged for a single daily score. The single daily scores for the week prior to the week 4 study assessment were summed and averaged to produce a mean daily VMS bothersomeness for week 4.
- Bothersomeness of Hot Flashes -- Week 8 [ Time Frame: Week 8 ]Measured by self-report diary twice daily (day and night) for 7 days. Bothersomeness ratings ranged from 0 to 3 with lower numbers being less bothersome and higher numbers being more bothersome. Data from the day and night bothersomeness ratings were averaged for a single daily score. The single daily scores for the week prior to the week 8 study assessment were summed and averaged to produce a mean daily VMS bothersomeness for week 8.
- Perceived Hot Flash Interference (Hot Flash Related Daily Interference Scale; HFRDIS) -- Week 4 [ Time Frame: Week 4 ]The perceived hot flash related daily interference scale (HFRDIS) is a tool for assessing the impact of hot flashes on quality of life. There are 10 questions with each having a score ranging from 0 to 10. The scores from each question are summed for a total score ranging from 0 to 100. Lower numbers indicate less interference and higher numbers indicate more interference.
- Perceived Hot Flash Interference (Hot Flash Related Daily Interference Scale; HFRDIS) -- Week 8 [ Time Frame: Week 8 ]The perceived hot flash related daily interference scale (HFRDIS) is a tool for assessing the impact of hot flashes on quality of life. There are 10 questions with each having a score ranging from 0 to 10. The scores from each question are summed for a total score ranging from 0 to 100. Lower numbers indicate less interference and higher numbers indicate more interference.

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Ages Eligible for Study: | 40 Years to 62 Years (Adult) |
Sexes Eligible for Study: | Female |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- Females aged 40-62 years
- Postmenopausal or perimenopausal
- Having bothersome hot flashes
- In general good health
- Signed informed consent
Exclusion Criteria:
- Recent use of systemic hormone therapy or hormonal contraceptives
- Recent use of any prescribed, over-the-counter or herbal therapies that are taken specifically for hot flashes
- Recent use of selective estrogen receptor modulators (SERMS) or aromatase inhibitors
- Recent use of psychotropic medications, including SSRIs (selective serotonin reuptake inhibitors), serotonin-norepinephrine reuptake inhibitors (SNRIs), MAOIs (monoamine oxidase inhibitors), and other antidepressants and anxiolytics.
- Known hypersensitivity or contraindications (reasons not to take) to venlafaxine, estrogen, or progestins
- Not using a medically approved method of birth control, if sexually active and not 12 or more months since last menstrual period
- Recent drug or alcohol abuse
- Lifetime diagnosis of psychosis or bipolar disorder
- Suicide attempt in the past 3 years or any current suicidal ideation
- Current major depression (assessed during screening)
- Pregnancy, intending pregnancy, or breast feeding
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History of:
- Pre-breast cancer or high-risk breast cancer condition
- Abnormal bleeding suggestive of endometrial pre-cancer or endometrial hyperplasia
- Asthma, diabetes mellitus, epilepsy, and migraine disorders that are not stable or under medical management
- Abnormal screening blood tests
- Current participation in another drug trial or intervention study
- Inability or unwillingness to complete the study procedures

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01418209
United States, Massachusetts | |
Massachusetts General Hospital, Harvard Medical School (HU) | |
Boston, Massachusetts, United States, 02114 | |
Brigham and Women's Hospital | |
Chestnut Hill, Massachusetts, United States, 02215 | |
United States, Pennsylvania | |
University of Pennsylvania, UP | |
Philadelphia, Pennsylvania, United States, 19104 | |
United States, Washington | |
Group Health Research Institute (GHRI) | |
Seattle, Washington, United States, 98101 |
Principal Investigator: | Andrea Z LaCroix, PhD | Fred Hutchinson Cancer Research Center | |
Principal Investigator: | Garnet Anderson, PhD | Fred Hutchinson Cancer Research Center | |
Principal Investigator: | Katherine Guthrie, PhD | Fred Hutchinson Cancer Research Center | |
Principal Investigator: | Lee S Cohen, MD | Massachusetts General Hospital/Harvard Medical School (HU) | |
Principal Investigator: | Hadine Joffe, MD, MSc | Massachusetts General Hospital/Harvard Medical School (HU) | |
Principal Investigator: | Katherine M Newton, PhD | Group Health Research Institute (GHRI) | |
Principal Investigator: | Susan D Reed, MD | University of Washington/Group Health Research Institute (GHRI) | |
Study Director: | Janet Carpenter, PhD, RN, FAAN | Indiana University School of Medicine | |
Principal Investigator: | Ellen W Freeman, PhD | University of Pennsylvania School of Medicine (UP) |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Katherine Guthrie, Principal Investigator, Fred Hutchinson Cancer Research Center |
ClinicalTrials.gov Identifier: | NCT01418209 History of Changes |
Other Study ID Numbers: |
MsFLASH-03 1U01AG032700-01 ( U.S. NIH Grant/Contract ) 1U01AG032699-01 ( U.S. NIH Grant/Contract ) |
First Posted: | August 17, 2011 Key Record Dates |
Results First Posted: | August 20, 2014 |
Last Update Posted: | August 27, 2014 |
Last Verified: | August 2014 |
Keywords provided by Katherine Guthrie, Fred Hutchinson Cancer Research Center:
Menopause Vasomotor Symptoms Estradiol Venlafaxine |
Additional relevant MeSH terms:
Hot Flashes Signs and Symptoms Estradiol Polyestradiol phosphate Progesterone Estradiol 3-benzoate Estradiol 17 beta-cypionate Estradiol valerate Venlafaxine Hydrochloride Estrogens Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs |
Contraceptive Agents Reproductive Control Agents Contraceptive Agents, Female Progestins Serotonin and Noradrenaline Reuptake Inhibitors Neurotransmitter Uptake Inhibitors Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Neurotransmitter Agents Antidepressive Agents, Second-Generation Antidepressive Agents Psychotropic Drugs |