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

Condition(s) targeted: Hot Flashes; Menopause; Vasomotor Disturbance

Intervention: Low-dose 17-ß-estradiol with progesterone taper (Drug); Venlafaxine XR (Drug); Placebo (Drug)

Phase: N/A

Status: Completed

Sponsored by: Fred Hutchinson Cancer Research Center

Official(s) and/or principal investigator(s):
Andrea Z LaCroix, PhD, Principal Investigator, Affiliation: Fred Hutchinson Cancer Research Center
Garnet Anderson, PhD, Principal Investigator, Affiliation: Fred Hutchinson Cancer Research Center
Katherine Guthrie, PhD, Principal Investigator, Affiliation: Fred Hutchinson Cancer Research Center
Lee S Cohen, MD, Principal Investigator, Affiliation: Massachusetts General Hospital/Harvard Medical School (HU)
Hadine Joffe, MD, MSc, Principal Investigator, Affiliation: Massachusetts General Hospital/Harvard Medical School (HU)
Katherine M Newton, PhD, Principal Investigator, Affiliation: Group Health Research Institute (GHRI)
Susan D Reed, MD, Principal Investigator, Affiliation: University of Washington/Group Health Research Institute (GHRI)
Janet Carpenter, PhD, RN, FAAN, Study Director, Affiliation: Indiana University School of Medicine
Ellen W Freeman, PhD, Principal Investigator, Affiliation: University of Pennsylvania School of Medicine (UP)

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.

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

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

Primary outcome:

Frequency of Hot Flashes (Vasomotor Symptom [VMS] Frequency) -- Week 4

Frequency of Hot Flashes (Daily Vasomotor Symptom [VMS] Frequency) -- Week 8

Secondary outcome:

Severity of Hot Flashes -- Week 4

Severity of Hot Flashes -- Week 8

Bothersomeness of Hot Flashes -- Week 4

Bothersomeness of Hot Flashes -- Week 8

Perceived Hot Flash Interference (Hot Flash Related Daily Interference Scale; HFRDIS) -- Week 4

Perceived Hot Flash Interference (Hot Flash Related Daily Interference Scale; HFRDIS) -- Week 8

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.

Minimum age: 40 Years. Maximum age: 62 Years. Gender(s): Female.

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

Massachusetts General Hospital, Harvard Medical School (HU), Boston, Massachusetts 02114, United States

Brigham and Women's Hospital, Chestnut Hill, Massachusetts 02215, United States

University of Pennsylvania, UP, Philadelphia, Pennsylvania 19104, United States

Group Health Research Institute (GHRI), Seattle, Washington 98101, United States

Starting date: November 2011
Last updated: August 20, 2014