MsFLASH-01: Escitalopram for Menopausal Symptoms in Midlife Women - Full Text View

Sponsor:	Fred Hutchinson Cancer Research Center
Collaborators:	National Institute on Aging (NIA) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) National Center for Complementary and Alternative Medicine (NCCAM) Office of Research on Women's Health (ORWH)
Information provided by:	Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:	NCT00894543

Purpose

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.

Condition	Intervention
Hot Flashes Menopause Vasomotor Symptoms	Drug: Escitalopram Other: Placebo

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

Resource links provided by NLM:

MedlinePlus related topics: Menopause

Drug Information available for: Serotonin Benzetimide Dexetimide Citalopram hydrobromide Citalopram Escitalopram Escitalopram oxalate

U.S. FDA Resources

Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:

Daily Frequency of Hot Flashes Per Day Assessed by Prospective Daily Diaries [ Time Frame: Baseline ] [ Designated as safety issue: No ]
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 [ Time Frame: week 4 minus baseline ] [ Designated as safety issue: No ]
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 [ Time Frame: week 8 minus baseline ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline ] [ Designated as safety issue: No ]
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 [ Time Frame: week 4 minus baseline ] [ Designated as safety issue: No ]
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 [ Time Frame: week 8 minus baseline ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline ] [ Designated as safety issue: No ]
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 [ Time Frame: week 4 minus baseline ] [ Designated as safety issue: No ]
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 [ Time Frame: week 8 minus baseline ] [ Designated as safety issue: No ]
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).

Enrollment:	205
Study Start Date:	July 2009
Study Completion Date:	June 2010
Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Escitalopram Escitalopram is a selective serotonin reuptake inhibitor (SSRI)	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 Name: Lexapro®.
Placebo Comparator: Placebo Inactive pill	Other: Placebo Inactive pill (1 pill or 2 pills) daily for the 8-11 weeks of the trial.

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

Ages Eligible for Study:	40 Years to 62 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00894543

Locations

United States, California
Northern California Kaiser, Division of Research
Oakland, California, United States, 94612
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Massachusetts General Hospital, Harvard Medical School
Boston, Massachusetts, United States, 02114
Brigham and Women's Hospital
Chestnut Hill, Massachusetts, United States, 02467
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Institute on Aging (NIA)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Center for Complementary and Alternative Medicine (NCCAM)

Office of Research on Women's Health (ORWH)

Investigators

Principal Investigator:	Ellen W Freeman, PhD	University of Pennsylvania Medical Center
Principal Investigator:	Andrea Z LaCroix, PhD	Fred Hutchinson Cancer Research Center
Principal Investigator:	Garnet L Anderson, PhD	Fred Hutchinson Cancer Research Center
Study Chair:	Kris Ensrud, MD	University of Minnesota - Clinical and Translational Science Institute

More Information

Additional Information:

MsFLASH Participant Website This link exits the ClinicalTrials.gov site

Publications:

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.

Responsible Party:	Andrea LaCroix, Garnet Anderson, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:	NCT00894543 History of Changes
Other Study ID Numbers:	MsFLASH-01, 1 U01 AG032699-01, 1 U01 AG032656-01
Study First Received:	May 5, 2009
Results First Received:	February 17, 2011
Last Updated:	August 1, 2011
Health Authority:	United States: Federal Government

Keywords provided by Fred Hutchinson Cancer Research Center:

Hot flashes
Menopause
Vasomotor symptoms

Additional relevant MeSH terms:

Hot Flashes
Signs and Symptoms
Dexetimide
Citalopram
Serotonin Uptake Inhibitors
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Parasympatholytics
Autonomic Agents

Peripheral Nervous System Agents
Physiological Effects of Drugs
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Neurotransmitter Uptake Inhibitors
Serotonin Agents

ClinicalTrials.gov processed this record on February 09, 2012