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
  Purpose

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.


Condition Intervention
Hot Flashes
Menopause
Vasomotor Disturbance
Drug: Low-dose 17-ß-estradiol with progesterone taper
Drug: Venlafaxine XR
Drug: 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: MsFLASH-03: Comparative Efficacy of Low-Dose Estradiol and the SNRI Venlafaxine XR for Treatment of Menopausal Symptoms

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 339
Study Start Date: November 2011
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Low-dose 17-ß-estradiol with progesterone taper 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®.
Active Comparator: Venlafaxine XR 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®
Placebo Comparator: Placebo Drug: Placebo
The placebo is an inactive pill that looks like the active medication.

Detailed Description:

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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01418209

Locations
United States, Massachusetts
Massachusetts General Hospital, Harvard Medical School (HU)
Boston, Massachusetts, United States, 02114
Brigham and Women's Hospital
Chestnut Hill, Massachusetts, United States, 02215
United States, Pennsylvania
University of Pennsylvania, UP
Philadelphia, Pennsylvania, United States, 19104
United States, Washington
Group Health Research Institute (GHRI)
Seattle, Washington, United States, 98101
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
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)
  More Information

No publications provided by Fred Hutchinson Cancer Research Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Katherine Guthrie, Principal Investigator, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01418209     History of Changes
Other Study ID Numbers: MsFLASH-03, 1U01AG032700-01, 1U01AG032699-01
Study First Received: August 15, 2011
Results First Received: June 18, 2014
Last Updated: August 20, 2014
Health Authority: United States: Federal Government

Keywords provided by Fred Hutchinson Cancer Research Center:
Menopause
Vasomotor
Symptoms
Estradiol
Venlafaxine

Additional relevant MeSH terms:
Hot Flashes
Signs and Symptoms
Estradiol
Polyestradiol phosphate
Progesterone
Estradiol valerate
Estradiol 17 beta-cypionate
Estradiol 3-benzoate
Venlafaxine
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Contraceptive Agents
Reproductive Control Agents
Therapeutic Uses
Contraceptive Agents, Female
Progestins
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 28, 2014