MsFLASH-03: Comparative Efficacy of Low-Dose Estradiol and Venlafaxine XR for Treatment of Menopausal Symptoms

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Katherine Guthrie, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01418209
First received: August 15, 2011
Last updated: August 20, 2014
Last verified: August 2014

August 15, 2011
August 20, 2014
November 2011
January 2013   (final data collection date for primary outcome measure)
  • Frequency of Hot Flashes (Vasomotor Symptom [VMS] Frequency) -- Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    Measured by self-report diary twice daily (day and night). The day and night frequencies were summed to produce a single number of hot flashes per day. The single number of hot flashes per day were summed and averaged for one week prior to the week 4 study assessment to produce a mean daily frequency for week 4.
  • Frequency of Hot Flashes (Daily Vasomotor Symptom [VMS] Frequency) -- Week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    Measured by self-report diary twice daily (day and night). The day and night frequencies were summed to produce a single number of hot flashes per day. The single number of hot flashes per day were summed and averaged for one week prior to the week 8 study assessment to produce a mean daily frequency for week 8.
  • Frequency of hot flashes [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Measured by self-report diary twice daily for 7 days
  • Bothersomeness of hot flashes [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Measured by self-report diary twice daily for 7 days.
  • Severity of hot flashes [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Measured by self-report diary twice daily for 7 days
Complete list of historical versions of study NCT01418209 on ClinicalTrials.gov Archive Site
  • Severity of Hot Flashes -- Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    Measured by self-report diary twice daily (day and night) for 7 days. Severity ratings ranged from 0 to 3 with lower numbers being less severe and higher numbers being more severe. Data from the day and night severity ratings were averaged for a single daily score. The single daily scores for the week prior to the week 4 study assessment were summed and averaged to produce a mean daily VMS severity for week 4.
  • Severity of Hot Flashes -- Week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    Measured by self-report diary twice daily (day and night) for 7 days. Severity ratings ranged from 0 to 3 with lower numbers being less severe and higher numbers being more severe. Data from the day and night severity ratings were averaged for a single daily score. The single daily scores for the week prior to the week 8 study assessment were summed and averaged to produce a mean daily VMS severity for week 8.
  • Bothersomeness of Hot Flashes -- Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    Measured by self-report diary twice daily (day and night) for 7 days. Bothersomeness ratings ranged from 0 to 3 with lower numbers being less bothersome and higher numbers being more bothersome. Data from the day and night bothersomeness ratings were averaged for a single daily score. The single daily scores for the week prior to the week 4 study assessment were summed and averaged to produce a mean daily VMS bothersomeness for week 4.
  • Bothersomeness of Hot Flashes -- Week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    Measured by self-report diary twice daily (day and night) for 7 days. Bothersomeness ratings ranged from 0 to 3 with lower numbers being less bothersome and higher numbers being more bothersome. Data from the day and night bothersomeness ratings were averaged for a single daily score. The single daily scores for the week prior to the week 8 study assessment were summed and averaged to produce a mean daily VMS bothersomeness for week 8.
  • Perceived Hot Flash Interference (Hot Flash Related Daily Interference Scale; HFRDIS) -- Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    The perceived hot flash related daily interference scale (HFRDIS) is a tool for assessing the impact of hot flashes on quality of life. There are 10 questions with each having a score ranging from 0 to 10. The scores from each question are summed for a total score ranging from 0 to 100. Lower numbers indicate less interference and higher numbers indicate more interference.
  • Perceived Hot Flash Interference (Hot Flash Related Daily Interference Scale; HFRDIS) -- Week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    The perceived hot flash related daily interference scale (HFRDIS) is a tool for assessing the impact of hot flashes on quality of life. There are 10 questions with each having a score ranging from 0 to 10. The scores from each question are summed for a total score ranging from 0 to 100. Lower numbers indicate less interference and higher numbers indicate more interference.
  • Sleep disturbance [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    As measured by sleep diaries and possibly a sleep monitor wrist-device worn at home 7 days at the start and end of the study.
  • Depression (depressive symptoms) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Measured by self-report responses to questionnaire
  • Anxiety [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Measured by self-report responses to questionnaire
  • Sexual function [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Measured by self-report responses to questionnaire
Not Provided
Not Provided
 
MsFLASH-03: Comparative Efficacy of Low-Dose Estradiol and Venlafaxine XR for Treatment of Menopausal Symptoms
MsFLASH-03: Comparative Efficacy of Low-Dose Estradiol and the SNRI Venlafaxine XR for Treatment of Menopausal Symptoms

The primary objective of this study is to determine the efficacy of both low-dose oral (by mouth) 17-ß-estradiol and the non-hormonal drug venlafaxine XR compared to placebo in reducing hot flashes. Included in this objective is the intention to compare venlafaxine XR to estradiol therapy, to provide evidence of the relative efficacy of venlafaxine to what is currently considered the most established but also a controversial therapy. 17-ß-estradiol is a type of estrogen. Venlafaxine XR is the extended release (XR) version of venlafaxine. Venlafaxine XR is an serotonin-norepinephrine reuptake inhibitor (SNRI). A placebo is a substance containing no medication.

The MsFLASH-03 study (Menopausal Strategies: Finding Lasting Answers for Symptoms and Health - 03), Comparative Efficacy of Low-Dose Estradiol and the SNRI Venlafaxine XR for Treatment of Menopausal Symptoms, is a randomized, double-blind, placebo-controlled, three 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 oral estradiol, venlafaxine, or placebo; followed by 14 days of drug taper for those on venlafaxine and 14 days of progesterone treatment for those on estradiol; followed by 2 weeks with no treatment for all groups; and a telephone follow-up post-treatment.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Hot Flashes
  • Menopause
  • Vasomotor Disturbance
  • Drug: Low-dose 17-ß-estradiol with progesterone taper
    Low-dose 17-ß-estradiol oral (by mouth), 0.5 mg once per day for 8 (eight) weeks. 17-ß-estradiol is approved by the US Food and Drug Administration (FDA) and is indicated for the treatment of menopausal symptoms. ß is the Greek symbol for beta; the symbol and the word are used interchangeably. The 8 week estradiol treatment is followed by 14 days (2 weeks) of progesterone taper (as medroxy-progesterone 10 mg/day).
    Other Name: The brand name of estradiol being used in this study is Estrace®.
  • Drug: Venlafaxine XR
    Venlafaxine oral (by mouth) 37.5 mg once per day for 1 (one) week, then 75 mg once per day for 7 (seven) weeks. Venlafaxine XR should not be taken while also taking monoamine oxidase inhibitors (MAOIs). Venlafaxine XR is approved by the US Food and Drug Administration (FDA) for treatment of depression, generalized anxiety disorder, social anxiety disorder, and panic disorder, and is available by prescription. Venlafaxine XR is not FDA-approved for the treatment of hot flashes, although prior studies have indicated that it is useful for treating hot flashes and vasomotor symptoms. After the 8-week venlafaxine XR study treatment period, women will receive a tapering dose of venlafaxine XR 37.5 mg once per day for 14 days (2 weeks).
    Other Name: The brand name of venlafaxine XR that is being used in this study is Effexor XR®
  • Drug: Placebo
    The placebo is an inactive pill that looks like the active medication.
  • Active Comparator: Low-dose 17-ß-estradiol with progesterone taper
    Intervention: Drug: Low-dose 17-ß-estradiol with progesterone taper
  • Active Comparator: Venlafaxine XR
    Intervention: Drug: Venlafaxine XR
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
339
January 2013
January 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Females aged 40-62 years
  • Postmenopausal or perimenopausal
  • Having bothersome hot flashes
  • In general good health
  • Signed informed consent

Exclusion Criteria:

  • Recent use of systemic hormone therapy or hormonal contraceptives
  • Recent use of any prescribed, over-the-counter or herbal therapies that are taken specifically for hot flashes
  • Recent use of selective estrogen receptor modulators (SERMS) or aromatase inhibitors
  • Recent use of psychotropic medications, including SSRIs (selective serotonin reuptake inhibitors), serotonin-norepinephrine reuptake inhibitors (SNRIs), MAOIs (monoamine oxidase inhibitors), and other antidepressants and anxiolytics.
  • Known hypersensitivity or contraindications (reasons not to take) to venlafaxine, estrogen, or progestins
  • Not using a medically approved method of birth control, if sexually active and not 12 or more months since last menstrual period
  • Recent drug or alcohol abuse
  • Lifetime diagnosis of psychosis or bipolar disorder
  • Suicide attempt in the past 3 years or any current suicidal ideation
  • Current major depression (assessed during screening)
  • Pregnancy, intending pregnancy, or breast feeding
  • History of:

    • Pre-breast cancer or high-risk breast cancer condition
    • Abnormal bleeding suggestive of endometrial pre-cancer or endometrial hyperplasia
    • Asthma, diabetes mellitus, epilepsy, and migraine disorders that are not stable or under medical management
  • Abnormal screening blood tests
  • Current participation in another drug trial or intervention study
  • Inability or unwillingness to complete the study procedures
Female
40 Years to 62 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01418209
MsFLASH-03, 1U01AG032700-01, 1U01AG032699-01
Yes
Katherine Guthrie, Fred Hutchinson Cancer Research Center
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)
Principal Investigator: Andrea Z LaCroix, PhD Fred Hutchinson Cancer Research Center
Principal Investigator: Garnet Anderson, PhD Fred Hutchinson Cancer Research Center
Principal Investigator: Katherine Guthrie, PhD Fred Hutchinson Cancer Research Center
Principal Investigator: Lee S Cohen, MD Massachusetts General Hospital/Harvard Medical School (HU)
Principal Investigator: Hadine Joffe, MD, MSc Massachusetts General Hospital/Harvard Medical School (HU)
Principal Investigator: Katherine M Newton, PhD Group Health Research Institute (GHRI)
Principal Investigator: Susan D Reed, MD University of Washington/Group Health Research Institute (GHRI)
Study Director: Janet Carpenter, PhD, RN, FAAN Indiana University School of Medicine
Principal Investigator: Ellen W Freeman, PhD University of Pennsylvania School of Medicine (UP)
Fred Hutchinson Cancer Research Center
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP