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MsFLASH-01: Escitalopram for Menopausal Symptoms in Midlife Women

Primary Purpose

Hot Flashes, Menopause, Vasomotor Symptoms

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Escitalopram

Placebo

About this trial

This is an interventional treatment trial for Hot Flashes focused on measuring Hot flashes, Menopause, Vasomotor symptoms

Eligibility Criteria

40 Years - 62 Years (Adult)FemaleAccepts Healthy Volunteers

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.

Sites / Locations

Northern California Kaiser, Division of Research
Indiana University
Massachusetts General Hospital, Harvard Medical School
Brigham and Women's Hospital
University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Escitalopram

Placebo

Arm Description

Escitalopram is a selective serotonin reuptake inhibitor (SSRI)

Inactive pill

Outcomes

Primary Outcome Measures

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.

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.

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.

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).

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).

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).

Secondary Outcome Measures

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).

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).

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).

Full Information

NCT ID

NCT00894543

First Posted

May 5, 2009

Last Updated

March 5, 2013

Sponsor

Fred Hutchinson Cancer Center

Collaborators

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)

1. Study Identification

Unique Protocol Identification Number

NCT00894543

Brief Title

MsFLASH-01: Escitalopram for Menopausal Symptoms in Midlife Women

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2013

Overall Recruitment Status

Completed

Study Start Date

July 2009 (undefined)

Primary Completion Date

June 2010 (Actual)

Study Completion Date

June 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Fred Hutchinson Cancer Center

Collaborators

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hot Flashes, Menopause, Vasomotor Symptoms

Keywords

Hot flashes, Menopause, Vasomotor symptoms

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

205 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Escitalopram

Arm Type

Active Comparator

Arm Description

Escitalopram is a selective serotonin reuptake inhibitor (SSRI)

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Inactive pill

Intervention Type

Drug

Intervention Name(s)

Escitalopram

Other Intervention Name(s)

Lexapro®.

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

Daily Frequency of Hot Flashes Per Day Assessed by Prospective Daily Diaries

Description

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

Title

Change in Daily Frequency of Hot Flashes Between Baseline and Week 4 as Assessed by Prospective Daily Diaries

Description

Time Frame

week 4 minus baseline

Title

Change in Daily Frequency of Hot Flashes Between Baseline and Week 8 as Assessed by Prospective Daily Diaries

Description

Time Frame

week 8 minus baseline

Title

Daily Severity of Hot Flashes Assessed by Prospective Daily Diaries

Description

Time Frame

Baseline

Title

Change in Daily Severity of Hot Flashes Between Baseline and Week 4 as Assessed by Prospective Daily Diaries

Description

Time Frame

week 4 minus baseline

Title

Change in Daily Severity of Hot Flashes Between Baseline and Week 8 as Assessed by Prospective Daily Diaries

Description

Time Frame

week 8 minus baseline

Secondary Outcome Measure Information:

Title

Daily Hot Flash Bother, Recorded on Daily Diaries

Description

Time Frame

Baseline

Title

Change in Daily Hot Flash Bother Between Baseline and Week 4 as Recorded on Daily Diaries

Description

Time Frame

week 4 minus baseline

Title

Secondary Outcome: Change in Daily Hot Flash Bother Between Baseline and Week 8 as Recorded on Daily Diaries

Description

Time Frame

week 8 minus baseline

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

62 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ellen W Freeman, PhD

Organizational Affiliation

University of Pennsylvania Medical Center

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Andrea Z LaCroix, PhD

Organizational Affiliation

Fred Hutchinson Cancer Center

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Garnet L Anderson, PhD

Organizational Affiliation

Fred Hutchinson Cancer Center

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Kris Ensrud, MD

Organizational Affiliation

University of Minnesota

Official's Role

Study Chair

Facility Information:

Facility Name

Northern California Kaiser, Division of Research

City

Oakland

State/Province

California

ZIP/Postal Code

94612

Country

United States

Facility Name

Indiana University

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

Massachusetts General Hospital, Harvard Medical School

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Brigham and Women's Hospital

City

Chestnut Hill

State/Province

Massachusetts

ZIP/Postal Code

02467

Country

United States

Facility Name

University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

21245182

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 controlled trial. JAMA. 2011 Jan 19;305(3):267-74. doi: 10.1001/jama.2010.2016.

Results Reference

result

PubMed Identifier

22480818

Citation

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. Epub 2012 Apr 3.

Results Reference

result

PubMed Identifier

22433978

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 flashes: a randomized controlled trial. Menopause. 2012 Aug;19(8):848-55. doi: 10.1097/gme.0b013e3182476099.

Results Reference

result

PubMed Identifier

22353950

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.

Results Reference

result

PubMed Identifier

23031421

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 controlled trial. Maturitas. 2012 Dec;73(4):361-8. doi: 10.1016/j.maturitas.2012.09.006. Epub 2012 Sep 30.

Results Reference

result

PubMed Identifier

23435022

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 for symptoms and health research network. Menopause. 2013 Mar;20(3):261-8. doi: 10.1097/GME.0b013e31826d3108.

Results Reference

result

PubMed Identifier

32701665

Citation

Diem SJ, LaCroix AZ, Reed SD, Larson JC, Newton KM, Ensrud KE, Woods NF, Guthrie KA. Effects of pharmacologic and nonpharmacologic interventions on menopause-related quality of life: a pooled analysis of individual participant data from four MsFLASH trials. Menopause. 2020 Oct;27(10):1126-1136. doi: 10.1097/GME.0000000000001597.

Results Reference

derived

PubMed Identifier

29165623

Citation

Guthrie KA, Larson JC, Ensrud KE, Anderson GL, Carpenter JS, Freeman EW, Joffe H, LaCroix AZ, Manson JE, Morin CM, Newton KM, Otte J, Reed SD, McCurry SM. Effects of Pharmacologic and Nonpharmacologic Interventions on Insomnia Symptoms and Self-reported Sleep Quality in Women With Hot Flashes: A Pooled Analysis of Individual Participant Data From Four MsFLASH Trials. Sleep. 2018 Jan 1;41(1):zsx190. doi: 10.1093/sleep/zsx190.

Results Reference

derived

PubMed Identifier

26241433

Citation

Guthrie KA, LaCroix AZ, Ensrud KE, Joffe H, Newton KM, Reed SD, Caan B, Carpenter JS, Cohen LS, Freeman EW, Larson JC, Manson JE, Rexrode K, Skaar TC, Sternfeld B, Anderson GL. Pooled Analysis of Six Pharmacologic and Nonpharmacologic Interventions for Vasomotor Symptoms. Obstet Gynecol. 2015 Aug;126(2):413-422. doi: 10.1097/AOG.0000000000000927.

Results Reference

derived

PubMed Identifier

23760428

Citation

Newton KM, Carpenter JS, Guthrie KA, Anderson GL, Caan B, Cohen LS, Ensrud KE, Freeman EW, Joffe H, Sternfeld B, Reed SD, Sherman S, Sammel MD, Kroenke K, Larson JC, Lacroix AZ. Methods for the design of vasomotor symptom trials: the menopausal strategies: finding lasting answers to symptoms and health network. Menopause. 2014 Jan;21(1):45-58. doi: 10.1097/GME.0b013e31829337a4.

Results Reference

derived

Learn more about this trial

MsFLASH-01: Escitalopram for Menopausal Symptoms in Midlife Women

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