Hot Flashes, Menopause, Vasomotor Symptoms
Conditions
Keywords
Hot flashes, Menopause, Vasomotor symptoms
Brief summary
The purpose of this study is to test whether a medication reduces the number, severity and bothersomeness of menopausal hot flashes. Escitalopram (also called Lexapro®) is a selective serotonin reuptake inhibitor (SSRI). It is sold by prescription for depression and general anxiety disorder. An SSRI increases serotonin, a brain substance that is believed to influence mood. Serotonin may also affect brain levels of estradiol, a hormone related to hot flashes. This research study will test whether escitalopram reduces menopausal hot flashes.
Detailed description
The MsFLASH-01 study, Efficacy of a Selective Serotonin Reuptake Inhibitor (SSRI) for Menopausal Symptoms in Midlife Women is a randomized, double-blind, placebo-controlled, parallel arm clinical trial. The design includes: 3 weeks of daily recording of hot flashes prior to drug treatment; 8 weeks of double-blind treatment with escitalopram or placebo with dose escalation at 4 weeks among non-responders; 1 week of drug taper for those on higher dose, followed by 2 weeks with no treatment; and a telephone follow-up post-treatment. This study is one of five clinical trials to be conducted as part of the Menopause Strategies - Finding Lasting Answers for Symptoms and Health (MsFLASH) study, a network of investigators and clinical trials designed to find new ways to alleviate the most common, bothersome symptoms of the menopausal transition.
Interventions
DRUGEscitalopram
10 mg (1 pill) escitalopram daily for the first four weeks. Dose increased to 20 mg (2 pills) escitalopram daily if relief from hot flashes has not occurred during the first four weeks of the daily 10 mg dose.
OTHERPlacebo
Inactive pill (1 pill or 2 pills) daily for the 8-11 weeks of the trial.
Sponsors
National Institute on Aging (NIA)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Center for Complementary and Integrative Health (NCCIH)
Office of Research on Women's Health (ORWH)
Fred Hutchinson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 62 Years
Healthy volunteers
Yes
Inclusion criteria
, Common to all MsFLASH Studies: * Females aged 40-62 years. * Menopausal, including: * Women with a uterus who have skipped 2 or more menstrual cycles with an amenorrhea interval ≥60 days in the past 12 months. * Women who have had a bi-lateral oophorectomy (surgical removal of both ovaries). * Women without a uterus who still have ovaries, under certain conditions determined during screening. * Having bothersome hot flashes. * In general good health as determined by medical history and physical measures. * Signed informed consent.
Exclusion criteria
, Common to all MsFLASH Studies: * Use of hormone therapy or hormonal contraceptives during the 2 months before enrollment and for the duration of the study. Certain exceptions apply, determined during screening. * Use of any other therapy that is taken specifically for hot flashes, including prescription, over-the-counter, or herbal therapies in the past month and duration of the study. * Any current severe or unstable medical illness. * Uncontrolled hypertension (\>160/100) or resting heart rate \>110. * History of endometrial or ovarian cancer; MI, angina, or cerebrovascular events. * Pregnancy, intending pregnancy, breast feeding. * Current participation in another drug trial or intervention study. * Inability or unwillingness to complete the study procedures. * Certain other conditions, determined during screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Daily Severity of Hot Flashes Between Baseline and Week 8 as Assessed by Prospective Daily Diaries | week 8 minus baseline | Change in daily hot flash severity between baseline & week 8 was calculated as mean difference. Baseline severity ratings were calculated as daily mean ratings for the first two screening weeks pre-baseline. Week 8 severity ratings were calculated as daily mean ratings during the week before week 8. Modified intention to treat analysis included all randomized participants who provided diary data, which were analyzed regardless of adherence to treatment assignment. Hot flash severity was rated as 1 (mild), 2 (moderate), or 3 (severe) as adopted from the Study of Women Across the Nation (SWAN). |
| Change in Daily Frequency of Hot Flashes Between Baseline and Week 8 as Assessed by Prospective Daily Diaries | week 8 minus baseline | Change in daily hot flash frequency was calculated as the daily mean difference between baseline and week 8. Baseline was calculated as the daily mean of the frequencies for the first two screening weeks. Week 8 was calculated as the daily mean of the daily frequencies during the week prior to the week 8 visit. |
| Daily Severity of Hot Flashes Assessed by Prospective Daily Diaries | Baseline | Daily hot flash severity scores were calculated by by selecting the highest severity rating for hot flashes or night sweats for each woman in each 24-hour day. The score was set to missing on on any day data were missing or or hot flashes equaled 0. The daily mean of daily ratings for the first 2 screening weeks is reported. Hot flash severity was rated as 1 (mild), 2 (moderate), or 3 (severe) as adopted from the Study of Women Across the Nation (SWAN). |
| Change in Daily Severity of Hot Flashes Between Baseline and Week 4 as Assessed by Prospective Daily Diaries | week 4 minus baseline | Change in daily hot flash severity from baseline to week 4 was calculated as the mean difference in hot flash severity ratings between baseline and week 4. Baseline was calculated as the daily mean from the first two weeks of hot flash severity ratings. Week 4 severity ratings were calculated as the daily mean from the ratings for the week prior to the week 4 visit. Hot flash severity was rated as 1 (mild), 2 (moderate), or 3 (severe) as adopted from the Study of Women Across the Nation (SWAN). |
| Daily Frequency of Hot Flashes Per Day Assessed by Prospective Daily Diaries | Baseline | Baseline hot flash frequency per day was calculated as the daily mean of the daily totals reported during the first two screening weeks. |
| Change in Daily Frequency of Hot Flashes Between Baseline and Week 4 as Assessed by Prospective Daily Diaries | week 4 minus baseline | Change in daily hot flash frequency was calculated as the daily mean difference between baseline and week 4. Baseline was calculated as the daily mean of the daily frequencies for the first two screening weeks. Week 4 was calculated as the daily mean of the daily frequencies during the week prior to the week 4 visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Daily Hot Flash Bother Between Baseline and Week 4 as Recorded on Daily Diaries | week 4 minus baseline | Change in daily hot flash bother was calculated as the mean difference between baseline and week 4. Baseline was calculated as the daily mean of the highest daily bother ratings during the first two screening weeks. Week 4 was calculated as the daily mean of the highest of the daily bother ratings during the week prior to the week 4 visit. Hot flash bother was rated as 1 (none), 2 (a little), 3 (moderately), or 4 (a lot) as adopted from the Study of Women Across the Nation (SWAN). |
| Secondary Outcome: Change in Daily Hot Flash Bother Between Baseline and Week 8 as Recorded on Daily Diaries | week 8 minus baseline | Change in daily hot flash bother between baseline & week 8 was calculated as mean difference. Baseline daily bother was the mean of the highest daily ratings for two screening weeks pre-baseline. Week 8 bother was daily mean of the highest daily bother ratings during the week before week 8. Modified intention to treat analysis included all randomized participants who provided diary data, which were analyzed regardless of adherence to treatment assignment. Hot flash bother was rated as 1 (none), 2 (a little), 3 (moderately), 4 (a lot) as adopted from the Study of Women Across the Nation (SWAN). |
| Daily Hot Flash Bother, Recorded on Daily Diaries | Baseline | Daily Hot flash bother scores were calculated by selecting the highest bother rating for hot flashes or night sweats for each woman in each 24-hour day. The score was set to missing on on any day data were missing or or hot flashes equaled 0. The daily mean of daily ratings for the first 2 screening weeks is reported. Hot flash bother was rated as 1 (none), 2 (a little), 3 (moderately), or 4 (a lot) as adopted from the Study of Women Across the Nation (SWAN). |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from July 2009 to June 2010. The trial was conducted at four MsFLASH network sites: University of Pennsylvania, Massachusetts General Hospital, Indiana University, Kaiser Permanente Division of Research in Oakland, California
Pre-assignment details
Following enrollment (signing the consent), symptoms and health were reviewed, brief physical exam conducted and urine pregnancy test administered, daily hot flash diaries completed for one week (in addition to two weeks before enrollment).
Participants by arm
| Arm | Count |
|---|---|
| Escitalopram Escitalopram is a selective serotonin reuptake inhibitor (SSRI). For the first four weeks, participants took 1 pill daily (escitalopram 10 mg or placebo). At 4 weeks, if hot flash frequency was not reduced by at least 50% or there was no decrease in severity, the dose was increased to 2 pills daily(escitalopram 20 mg or placebo) unless precluded by unacceptable adverse events. At 8 weeks, participants taking 1 pill per day stopped treatment; participants taking 2 pills per day tapered the dose over a week. | 104 |
| Placebo Inactive pill | 101 |
| Total | 205 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Baseline to Week 4 | No diary or lost or withdrew | 3 | 2 |
| Week 4 to Week 8 | No diary or lost or withdrew | 4 | 2 |
Baseline characteristics
| Characteristic | Escitalopram | Total | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 104 Participants | 205 Participants | 101 Participants |
| Age Continuous | 53.45 years STANDARD_DEVIATION 4.2 | 53.9 years STANDARD_DEVIATION 4 | 54.36 years STANDARD_DEVIATION 3.86 |
| Body Mass Index (BMI) 25-<30, kg/m^2 | 34 participants | 72 participants | 38 participants |
| Body Mass Index (BMI) <25, kg/m^2 | 32 participants | 54 participants | 22 participants |
| Body Mass Index (BMI) >=30, kg/m^2 | 38 participants | 78 participants | 40 participants |
| Body Mass Index (BMI) Missing data | 0 participants | 1 participants | 1 participants |
| Hysterectomy Don't know | 0 participants | 1 participants | 1 participants |
| Hysterectomy Hysterectomy | 13 participants | 26 participants | 13 participants |
| Hysterectomy Hysterectomy and oophorectomy | 11 participants | 19 participants | 8 participants |
| Hysterectomy None | 77 participants | 155 participants | 78 participants |
| Hysterectomy Oophorectomy only | 3 participants | 4 participants | 1 participants |
| Menopausal Status Early transition | 3 participants | 6 participants | 3 participants |
| Menopausal Status Late transition | 17 participants | 32 participants | 15 participants |
| Menopausal Status Postmenopause | 84 participants | 167 participants | 83 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 47 Participants | 95 Participants | 48 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 8 Participants | 4 Participants |
| Race (NIH/OMB) White | 53 Participants | 102 Participants | 49 Participants |
| Region of Enrollment United States | 104 participants | 205 participants | 101 participants |
| Sex: Female, Male Female | 104 Participants | 205 Participants | 101 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 54 / 104 | 62 / 101 |
| serious Total, serious adverse events | 0 / 104 | 0 / 101 |
Outcome results
Primary
Change in Daily Frequency of Hot Flashes Between Baseline and Week 4 as Assessed by Prospective Daily Diaries
Change in daily hot flash frequency was calculated as the daily mean difference between baseline and week 4. Baseline was calculated as the daily mean of the daily frequencies for the first two screening weeks. Week 4 was calculated as the daily mean of the daily frequencies during the week prior to the week 4 visit.
Time frame: week 4 minus baseline
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Escitalopram | Change in Daily Frequency of Hot Flashes Between Baseline and Week 4 as Assessed by Prospective Daily Diaries | -4.37 Hot flashes/day |
| Placebo | Change in Daily Frequency of Hot Flashes Between Baseline and Week 4 as Assessed by Prospective Daily Diaries | -2.49 Hot flashes/day |
Primary
Change in Daily Frequency of Hot Flashes Between Baseline and Week 8 as Assessed by Prospective Daily Diaries
Change in daily hot flash frequency was calculated as the daily mean difference between baseline and week 8. Baseline was calculated as the daily mean of the frequencies for the first two screening weeks. Week 8 was calculated as the daily mean of the daily frequencies during the week prior to the week 8 visit.
Time frame: week 8 minus baseline
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Escitalopram | Change in Daily Frequency of Hot Flashes Between Baseline and Week 8 as Assessed by Prospective Daily Diaries | -4.60 Hot flashes/day |
| Placebo | Change in Daily Frequency of Hot Flashes Between Baseline and Week 8 as Assessed by Prospective Daily Diaries | -3.20 Hot flashes/day |
Comparison: Based on data from the Herbal Alternatives for Menopause (HALT) study, MsFLASH estimated that 90 women in each treatment group provide 90% power to detect a difference between drug and placebo with a 2-sided alpha of 0.025 to account for two primary outcomes of hot flash frequency and severity.p-value: <0.001Regression, Linear
Primary
Change in Daily Severity of Hot Flashes Between Baseline and Week 4 as Assessed by Prospective Daily Diaries
Change in daily hot flash severity from baseline to week 4 was calculated as the mean difference in hot flash severity ratings between baseline and week 4. Baseline was calculated as the daily mean from the first two weeks of hot flash severity ratings. Week 4 severity ratings were calculated as the daily mean from the ratings for the week prior to the week 4 visit. Hot flash severity was rated as 1 (mild), 2 (moderate), or 3 (severe) as adopted from the Study of Women Across the Nation (SWAN).
Time frame: week 4 minus baseline
Population: Hot flash severity was rated as 1 (mild), 2 (moderate), or 3 (severe) as adapted from the Study of Women Across the Nation (SWAN).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Escitalopram | Change in Daily Severity of Hot Flashes Between Baseline and Week 4 as Assessed by Prospective Daily Diaries | -0.43 Scores on a scale |
| Placebo | Change in Daily Severity of Hot Flashes Between Baseline and Week 4 as Assessed by Prospective Daily Diaries | -0.23 Scores on a scale |
Primary
Change in Daily Severity of Hot Flashes Between Baseline and Week 8 as Assessed by Prospective Daily Diaries
Change in daily hot flash severity between baseline & week 8 was calculated as mean difference. Baseline severity ratings were calculated as daily mean ratings for the first two screening weeks pre-baseline. Week 8 severity ratings were calculated as daily mean ratings during the week before week 8. Modified intention to treat analysis included all randomized participants who provided diary data, which were analyzed regardless of adherence to treatment assignment. Hot flash severity was rated as 1 (mild), 2 (moderate), or 3 (severe) as adopted from the Study of Women Across the Nation (SWAN).
Time frame: week 8 minus baseline
Population: Hot flash severity was rated as 1 (mild), 2 (moderate), or 3 (severe) as adapted from the Study of Women Across the Nation (SWAN).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Escitalopram | Change in Daily Severity of Hot Flashes Between Baseline and Week 8 as Assessed by Prospective Daily Diaries | -0.53 Scores on a scale |
| Placebo | Change in Daily Severity of Hot Flashes Between Baseline and Week 8 as Assessed by Prospective Daily Diaries | -0.30 Scores on a scale |
Comparison: Based on data from the Herbal Alternatives for Menopause (HALT) study, MsFLASH estimated that 90 women in each treatment group provide 90% power to detect a difference between drug and placebo with a 2-sided alpha of 0.025 to account for two primary outcomes of hot flash frequency and severity.p-value: <0.001Regression, Linear
Primary
Daily Frequency of Hot Flashes Per Day Assessed by Prospective Daily Diaries
Baseline hot flash frequency per day was calculated as the daily mean of the daily totals reported during the first two screening weeks.
Time frame: Baseline
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Escitalopram | Daily Frequency of Hot Flashes Per Day Assessed by Prospective Daily Diaries | 9.88 Hot flashes/day |
| Placebo | Daily Frequency of Hot Flashes Per Day Assessed by Prospective Daily Diaries | 9.66 Hot flashes/day |
Primary
Daily Severity of Hot Flashes Assessed by Prospective Daily Diaries
Daily hot flash severity scores were calculated by by selecting the highest severity rating for hot flashes or night sweats for each woman in each 24-hour day. The score was set to missing on on any day data were missing or or hot flashes equaled 0. The daily mean of daily ratings for the first 2 screening weeks is reported. Hot flash severity was rated as 1 (mild), 2 (moderate), or 3 (severe) as adopted from the Study of Women Across the Nation (SWAN).
Time frame: Baseline
Population: Hot flash severity was rated as 1 (mild), 2 (moderate), or 3 (severe) as adapted from the Study of Women Across the Nation (SWAN).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Escitalopram | Daily Severity of Hot Flashes Assessed by Prospective Daily Diaries | 2.16 Scores on a scale |
| Placebo | Daily Severity of Hot Flashes Assessed by Prospective Daily Diaries | 2.19 Scores on a scale |
Secondary
Change in Daily Hot Flash Bother Between Baseline and Week 4 as Recorded on Daily Diaries
Change in daily hot flash bother was calculated as the mean difference between baseline and week 4. Baseline was calculated as the daily mean of the highest daily bother ratings during the first two screening weeks. Week 4 was calculated as the daily mean of the highest of the daily bother ratings during the week prior to the week 4 visit. Hot flash bother was rated as 1 (none), 2 (a little), 3 (moderately), or 4 (a lot) as adopted from the Study of Women Across the Nation (SWAN).
Time frame: week 4 minus baseline
Population: Twice daily rating for bother using response categories from the Study of Women Across the Nation (SWAN): 1 (not at all), 2 (very little), 3 (moderately), 4 (a lot).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Escitalopram | Change in Daily Hot Flash Bother Between Baseline and Week 4 as Recorded on Daily Diaries | -0.59 Scores on a scale |
| Placebo | Change in Daily Hot Flash Bother Between Baseline and Week 4 as Recorded on Daily Diaries | -0.29 Scores on a scale |
Secondary
Daily Hot Flash Bother, Recorded on Daily Diaries
Daily Hot flash bother scores were calculated by selecting the highest bother rating for hot flashes or night sweats for each woman in each 24-hour day. The score was set to missing on on any day data were missing or or hot flashes equaled 0. The daily mean of daily ratings for the first 2 screening weeks is reported. Hot flash bother was rated as 1 (none), 2 (a little), 3 (moderately), or 4 (a lot) as adopted from the Study of Women Across the Nation (SWAN).
Time frame: Baseline
Population: Twice daily rating for bother using response categories from the Study of Women Across the Nation (SWAN): 1 (not at all), 2 (very little), 3 (moderately), 4 (a lot).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Escitalopram | Daily Hot Flash Bother, Recorded on Daily Diaries | 3.12 Scores on a scale |
| Placebo | Daily Hot Flash Bother, Recorded on Daily Diaries | 3.16 Scores on a scale |
Secondary
Secondary Outcome: Change in Daily Hot Flash Bother Between Baseline and Week 8 as Recorded on Daily Diaries
Change in daily hot flash bother between baseline & week 8 was calculated as mean difference. Baseline daily bother was the mean of the highest daily ratings for two screening weeks pre-baseline. Week 8 bother was daily mean of the highest daily bother ratings during the week before week 8. Modified intention to treat analysis included all randomized participants who provided diary data, which were analyzed regardless of adherence to treatment assignment. Hot flash bother was rated as 1 (none), 2 (a little), 3 (moderately), 4 (a lot) as adopted from the Study of Women Across the Nation (SWAN).
Time frame: week 8 minus baseline
Population: Twice daily rating for bother using response categories from the Study of Women Across the Nation (SWAN): 1 (not at all), 2 (very little), 3 (moderately), 4 (a lot).~Modified intention to treat analysis included all randomized participants who provided diary data, which were analyzed regardless of adherence to treatment assignment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Escitalopram | Secondary Outcome: Change in Daily Hot Flash Bother Between Baseline and Week 8 as Recorded on Daily Diaries | -0.63 Scores on a scale |
| Placebo | Secondary Outcome: Change in Daily Hot Flash Bother Between Baseline and Week 8 as Recorded on Daily Diaries | -0.39 Scores on a scale |
p-value: 0.001Regression, Linear