Clinical trial NCT00894543: 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
Overall status: COMPLETED
Phase: NA
Conditions: Hot Flashes
Menopause
Vasomotor Symptoms
Keywords: Hot flashes
Menopause
Vasomotor symptoms
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: National Center for Complementary and Integrative Health (NCCIH)
name: Office of Research on Women's Health (ORWH)
First posted: 2009-05-07
Enrollment: 205
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 62
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Daily Frequency of Hot Flashes Per Day Assessed by Prospective Daily Diaries
timeFrame: Baseline
measure: Change in Daily Frequency of Hot Flashes Between Baseline and Week 4 as Assessed by Prospective Daily Diaries
timeFrame: week 4 minus baseline
measure: Change in Daily Frequency of Hot Flashes Between Baseline and Week 8 as Assessed by Prospective Daily Diaries
timeFrame: week 8 minus baseline
measure: Daily Severity of Hot Flashes Assessed by Prospective Daily Diaries
timeFrame: Baseline
measure: Change in Daily Severity of Hot Flashes Between Baseline and Week 4 as Assessed by Prospective Daily Diaries
timeFrame: week 4 minus baseline
measure: Change in Daily Severity of Hot Flashes Between Baseline and Week 8 as Assessed by Prospective Daily Diaries
timeFrame: week 8 minus baseline
Secondary outcomes:
measure: Daily Hot Flash Bother, Recorded on Daily Diaries
timeFrame: Baseline
measure: Change in Daily Hot Flash Bother Between Baseline and Week 4 as Recorded on Daily Diaries
timeFrame: week 4 minus baseline
measure: Secondary Outcome: Change in Daily Hot Flash Bother Between Baseline and Week 8 as Recorded on Daily Diaries
timeFrame: week 8 minus baseline
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Northern California Kaiser, Division of Research
state: California
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Boston
country: United States
facility: Massachusetts General Hospital, Harvard Medical School
state: Massachusetts
city: Chestnut Hill
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania Medical Center
name: Ellen W Freeman, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fred Hutchinson Cancer Center
name: Andrea Z LaCroix, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fred Hutchinson Cancer Center
name: Garnet L Anderson, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Minnesota
name: Kris Ensrud, MD
role: STUDY_CHAIR
References:
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.