MsFLASH-01: Escitalopram for Menopausal Symptoms in Midlife Women

Menopause Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00894543
• Other study ID #: MsFLASH-01
• Secondary ID: 1U01AG032699-011
• Status: Completed
• Phase: N/A
• First received: May 5, 2009
• Last updated: March 5, 2013
• Start date: July 2009
• Est. completion date: June 2010

Study information

• Verified date: March 2013
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 205
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 40 Years to 62 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hot Flashes
• Menopause
• Vasomotor Symptoms

Intervention

Drug:
• Escitalopram
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.

Other:
• Placebo
Inactive pill (1 pill or 2 pills) daily for the 8-11 weeks of the trial.

Locations

Country	Name	City	State
United States	Massachusetts General Hospital, Harvard Medical School	Boston	Massachusetts
United States	Brigham and Women's Hospital	Chestnut Hill	Massachusetts
United States	Indiana University	Indianapolis	Indiana
United States	Northern California Kaiser, Division of Research	Oakland	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (5)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Center for Complementary and Integrative Health (NCCIH), National Institute on Aging (NIA), Office of Research on Women's Health (ORWH)

Country where clinical trial is conducted

United States, 

References & Publications (6)

Carpenter JS, Guthrie KA, Larson JC, Freeman EW, Joffe H, Reed SD, Ensrud KE, LaCroix AZ. Effect of escitalopram on hot flash interference: a randomized, controlled trial. Fertil Steril. 2012 Jun;97(6):1399-404.e1. doi: 10.1016/j.fertnstert.2012.03.001. E — View Citation

Ensrud KE, Joffe H, Guthrie KA, Larson JC, Reed SD, Newton KM, Sternfeld B, Lacroix AZ, Landis CA, Woods NF, Freeman EW. Effect of escitalopram on insomnia symptoms and subjective sleep quality in healthy perimenopausal and postmenopausal women with hot f — View Citation

Freeman EW, Guthrie KA, Caan B, Sternfeld B, Cohen LS, Joffe H, Carpenter JS, Anderson GL, Larson JC, Ensrud KE, Reed SD, Newton KM, Sherman S, Sammel MD, LaCroix AZ. Efficacy of escitalopram for hot flashes in healthy menopausal women: a randomized contr — View Citation

Joffe H, Guthrie KA, Larson J, Cohen LS, Carpenter JS, Lacroix AZ, Freeman EW. Relapse of vasomotor symptoms after discontinuation of the selective serotonin reuptake inhibitor escitalopram: results from the menopause strategies: finding lasting answers f — View Citation

LaCroix AZ, Freeman EW, Larson J, Carpenter JS, Joffe H, Reed SD, Newton KM, Seguin RA, Sternfeld B, Cohen L, Ensrud KE. Effects of escitalopram on menopause-specific quality of life and pain in healthy menopausal women with hot flashes: a randomized cont — View Citation

Reed SD, Guthrie KA, Joffe H, Shifren JL, Seguin RA, Freeman EW. Sexual function in nondepressed women using escitalopram for vasomotor symptoms: a randomized controlled trial. Obstet Gynecol. 2012 Mar;119(3):527-38. doi: 10.1097/AOG.0b013e3182475fa4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline	No
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.	week 4 minus baseline	No
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.	week 8 minus baseline	No
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).	Baseline	No
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).	week 4 minus baseline	No
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).	week 8 minus baseline	No
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).	Baseline	No
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).	week 4 minus baseline	No
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).	week 8 minus baseline	No