MsFLASH-01: Escitalopram for Menopausal Symptoms in Midlife Women

Study Overview
=================
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.

Official Title
-----------------
Menopause Strategies: Finding Lasting Answers for Symptoms and Health: Efficacy of a Selective Serotonin Reuptake Inhibitor (SSRI) for Menopausal Symptoms in Midlife Women

Conditions
-----------------
Hot Flashes, Menopause, Vasomotor Symptoms

Intervention / Treatment
-----------------
* Drug: Escitalopram
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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. Exclusion Criteria, Specific to MsFLASH-01: Use of selective estrogen receptor modulators (SERMS) or aromatase inhibitors during the two months before enrollment. Use of gabapentin, pregabalin, triptans, warfarin (Coumadin®), or St. John's Wort. Known hypersensitivity to escitalopram (Lexapro®) or citalopram (Celexa®). Use of antidepressants during the past 30 days before starting Study 01, including SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), and anxiolytics. Not using a medically approved method of birth control, if sexually active and not 12 or more months since last menstrual period. History of liver, gall bladder, renal disease, or uncontrolled seizure disorder. Certain other conditions, determined during screening.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 62 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Escitalopram<br>Escitalopram is a selective serotonin reuptake inhibitor (SSRI) | Drug: Escitalopram<br>* 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.<br>* Other names: Lexapro®.;|
| Placebo Comparator: Placebo<br>Inactive pill | Other: Placebo<br>* Inactive pill (1 pill or 2 pills) daily for the 8-11 weeks of the trial.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline | 
| 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. | week 4 minus baseline | 
| 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. | week 8 minus baseline | 
| 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). | Baseline | 
| 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). | week 4 minus baseline | 
| 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). | week 8 minus baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline | 
| 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). | week 4 minus baseline | 
| 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). | week 8 minus baseline | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hot flashes, Menopause, Vasomotor symptoms