MsFLASH-01: Escitalopram for Menopausal Symptoms in Midlife Women

NCT00894543 | Completed Results DMC

• 3 other identifiers: MsFLASH-011U01AG032699-011U01AG032656-01
• Study Type: interventional
• Target: 205
• Locations: 1 country
• Sites: 5

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.

Conditions

Hot Flashes; Menopause; Vasomotor Symptoms

Keywords

Hot flashes; Menopause; Vasomotor symptoms

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (3)

• Daily Hot Flash Bother, Recorded on Daily Diaries

  Baseline

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

  week 4 minus baseline

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

  week 8 minus baseline

Study Arms (2)

Escitalopram

ACTIVE COMPARATOR

Escitalopram is a selective serotonin reuptake inhibitor (SSRI)

Drug: Escitalopram

Placebo

PLACEBO COMPARATOR

Inactive pill

Other: Placebo

Interventions

Escitalopram DRUG

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.

Also known as: Lexapro®.

Escitalopram

Placebo OTHER

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

Placebo

Eligibility Criteria

• Age: 40 Years - 62 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Institute on Aging (NIA): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• National Center for Complementary and Integrative Health (NCCIH): collaborator
• Office of Research on Women's Health (ORWH): collaborator

Study Sites (5)

Northern California Kaiser, Division of Research

Oakland, California, 94612, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Massachusetts General Hospital, Harvard Medical School

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Chestnut Hill, Massachusetts, 02467, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (10)

• 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.

  PMID: 21245182 RESULT

• 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.

  PMID: 22480818 RESULT

• 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.

  PMID: 22433978 RESULT

• 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.

  PMID: 22353950 RESULT

• 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.

  PMID: 23031421 RESULT

• 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.

  PMID: 23435022 RESULT

• 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.

  PMID: 32701665 DERIVED

• 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.

  PMID: 29165623 DERIVED

• 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.

  PMID: 26241433 DERIVED

• 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.

  PMID: 23760428 DERIVED

MeSH Terms

Conditions

Hot Flashes

Interventions

Escitalopram

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Although this was a community-based sample, the volunteers may be a select group motivated to seek treatment. An 8-week trial is brief, but data indicate that this interval is sufficient to determine long-term efficacy of a nonhormonal compound.

Results Point of Contact

• Title: Dr. Ellen W. Freeman
• Organization: University of Pennsylvania School of Medicine

freemane@mail.med.upenn.edu

215-349-5521

Study Officials

• Ellen W Freeman, PhD

  University of Pennsylvania Medical Center

  PRINCIPAL INVESTIGATOR

• Andrea Z LaCroix, PhD

  Fred Hutchinson Cancer Center

  PRINCIPAL INVESTIGATOR

• Garnet L Anderson, PhD

  Fred Hutchinson Cancer Center

  PRINCIPAL INVESTIGATOR

• Kris Ensrud, MD

  University of Minnesota

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 5, 2009
• First Posted: May 7, 2009
• Study Start: July 1, 2009
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: March 8, 2013
• Results First Posted: March 23, 2011

Record last verified: 2013-03

Locations

US (5)