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

This study has been completed.
Sponsor:
Collaborators:
National Institute on Aging (NIA)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Center for Complementary and Integrative Health (NCCIH)
Office of Research on Women's Health (ORWH)
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
Results First Received: June 18, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Hot Flashes
Menopause
Vasomotor Disturbance
Interventions: Drug: Low-dose 17-ß-estradiol with progesterone taper
Drug: Venlafaxine XR
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
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 14 days (2 weeks) of progesterone taper (as medroxy-progesterone 10 mg/day).
Venlafaxine XR 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).
Placebo Placebo: The placebo is an inactive pill that looks like the active medication.

Participant Flow:   Overall Study
    Low-dose 17-ß-Estradiol With Progesterone Taper   Venlafaxine XR   Placebo
STARTED   97   96   146 
COMPLETED   95   93   142 
NOT COMPLETED   2   3   4 
Withdrawal by Subject                1                0                1 
Did not provide hot flash diary data                1                3                3 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Randomized participants per trial arm

Reporting Groups
  Description
Low-dose 17-ß-estradiol With Progesterone Taper Low-dose 17-ß-estradiol: Low-dose 17-ß-estradiol oral (by mouth), 0.5 mg once per day for 8 (eight) weeks. After the 8-week treatment, women with a uterus will receive medroxyprogesterone 10 mg once per day for 2 weeks (14 days). 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.
Venlafaxine XR 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).
Placebo Placebo: The placebo is an inactive pill that looks like the active medication.
Total Total of all reporting groups

Baseline Measures
   Low-dose 17-ß-estradiol With Progesterone Taper   Venlafaxine XR   Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 97   96   146   339 
Age 
[Units: Years]
Mean (Standard Deviation)
 54.9  (4.1)   54.8  (3.7)   54.3  (3.8)   54.6  (3.8) 
Gender 
[Units: Participants]
       
Female   97   96   146   339 
Male   0   0   0   0 
Region of Enrollment 
[Units: Participants]
       
United States   97   96   146   339 
Body Mass Index (BMI) 
[Units: Kg/m^2]
Mean (Standard Deviation)
 28.5  (6.5)   29.3  (6.9)   27.6  (6.8)   28.3  (6.8) 
Smoking 
[Units: Participants]
       
Never   50   54   70   174 
Past   30   27   50   107 
Current   17   14   24   55 
Missing   0   1   2   3 
Alcohol use (drinks/week) 
[Units: Participants]
       
<7   71   77   117   265 
>=7   21   13   27   61 
Missing   5   6   2   13 
Marital status 
[Units: Participants]
       
Never married / Divorced / Widowed   38   40   49   127 
Married / living with partner   58   56   96   210 
Missing   1   0   1   2 
Education 
[Units: Participants]
       
<College graduate   48   48   70   166 
College graduate   49   48   75   172 
Missing   0   0   1   1 
Menopause status 
[Units: Participants]
       
Perimenopausal   14   16   22   52 
Postmenopausal   74   72   110   256 
Indeterminate   9   8   14   31 
Years since final menstrual period (postmenopausal only) 
[Units: Participants]
       
0 - 5   35   39   68   142 
6 - 10   23   20   29   72 
> 10   16   13   13   42 
Not postmenopausal   23   24   36   83 
Vasomotor symptom (VMS) number of participants with number of hot flashes / day 
[Units: Participants]
       
< 6   36   36   67   139 
6 - < 9   32   31   39   102 
9 - < 12   11   15   19   45 
>= 12   18   14   21   53 
Age at starting vasomotor symptoms (VMS), years of age 
[Units: Participants]
       
< 50   47   51   73   171 
>= 50   48   44   71   163 
Missing   2   1   2   5 
Insomnia Severity Index (ISI) Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 11.0  (6.3)   11.7  (6.0)   10.4  (5.8)   11.0  (6.0) 
[1] The Insomnia Severity Index (ISI) assesses level of insomnia, an inability to sleep. There are 7 questions, each ranging in a numerical rating from 0 (zero) to 4 with 0 indicating less insomnia and 4 indicating more insomnia. The numbers from each question are summed for a total score ranging from 0 to 28 with 0 indicating less insomnia and 28 indicating more insomnia.
Insomnia Severity Index (ISI) Score 
[Units: Participants]
       
No clinically significant insomnia (<= 7)   28   26   52   106 
Subthreshold insomnia (8 - 14)   40   39   54   133 
Clinical insomnia (moderate, 15 - 21)   21   25   32   78 
Clinical insomnia (severe, >= 22)   5   5   4   14 
Missing   3   1   4   8 
Pittsburgh Sleep Quality Index (PSQI) Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 7.6  (3.6)   7.6  (3.2)   7.3  (3.5)   7.5  (3.4) 
[1] The Pittsburgh Sleep Quality Index (PSQI) assesses quality of sleep. There are 7 questions. Each question is scored 0 (better quality sleep) to 3 (worse quality sleep). The scores from each question are summed to a total score, ranging from 0 (better quality sleep) to 21 (worse quality sleep).
Pittsburgh Sleep Quality Index (PSQI) Score 
[Units: Participants]
       
Good quality sleep (< 5)   23   14   30   67 
Moderate sleep quality (5 - < 8)   21   35   46   102 
Poor sleep quality (>= 8)   46   40   65   151 
Missing   7   7   5   19 
Patient Health Questionnaire (PHQ-9) Depression Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 3.9  (4.4)   3.0  (2.9)   3.4  (3.7)   3.4  (3.7) 
[1] The Patient Health Questionnaire (PHQ-9) assesses severity of depression. There are 10 questions with the first nine questions each scored from 0 to 3. The individual scores are summed to create a total score ranging from 0 to 45. Scores from 5 to >20 provisionally indicate, from lower to higher numbers, minimal symptoms to severe depression.
PHQ-9 Depression Score 
[Units: Participants]
       
No depression (0 - 4)   68   70   108   246 
Mild depression (5 - 9)   18   23   23   64 
Moderate depression (>= 10)   11   3   15   29 
Generalized Anxiety Disorder 7 (GAD-7) Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 3.0  (4.3)   2.2  (3.0)   2.4  (3.4)   2.5  (3.6) 
[1] Generalized Anxiety Disorder 7 (GAD-7) assesses generalized anxiety. There are 7 questions with each scored from 0 to 3. The scores from each question are summed to a total score ranging from 0 to 21. Lower scores are better.
Generalized Anxiety Disorder 7 (GAD-7) Score 
[Units: Participants]
       
No anxiety (0 - 4)   73   76   116   265 
Mild anxiety (5 - 9)   15   17   19   51 
Moderate anxiety (>= 10)   9   3   11   23 
Vasomotor Symptoms (VMS) as number of hot flashes [1] 
[Units: Number of hot flashes per day]
Mean (Standard Deviation)
 8.5  (5.7)   8.2  (5.5)   7.7  (4.8)   8.1  (5.3) 
[1] Vasomotor Symptoms (VMS) frequency measures the number of hot flashes during the day and during the night. The day and night frequencies are summed for a 24-hour score.
Severity of Hot Flashes [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 1.1  (0.5)   1.0  (0.5)   1.0  (0.4)   1.0  (0.5) 
[1] Severity of hot flashes is measured as a scale from 0 to 3. Lower numbers indicate less severity and higher numbers indicate more severity.
Bothersomeness of Hot Flashes [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 2.1  (0.5)   2.0  (0.5)   2.0  (0.5)   2.0  (0.5) 
[1] Bothersomeness of hot flashes is measured on a scale from 0 to 3. Lower numbers indicate less bother and higher numbers indicate more bother.
Perceived Hot Flash Interference (Hot Flash Related Daily Interference Scale; HFRDIS) [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 36.9  (23.8)   36.8  (23.4)   32.8  (21.3)   35.1  (22.6) 
[1] 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.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Frequency of Hot Flashes (Vasomotor Symptom [VMS] Frequency) -- Week 4   [ Time Frame: Week 4 ]

2.  Primary:   Frequency of Hot Flashes (Daily Vasomotor Symptom [VMS] Frequency) -- Week 8   [ Time Frame: Week 8 ]

3.  Secondary:   Severity of Hot Flashes -- Week 4   [ Time Frame: Week 4 ]

4.  Secondary:   Severity of Hot Flashes -- Week 8   [ Time Frame: Week 8 ]

5.  Secondary:   Bothersomeness of Hot Flashes -- Week 4   [ Time Frame: Week 4 ]

6.  Secondary:   Bothersomeness of Hot Flashes -- Week 8   [ Time Frame: Week 8 ]

7.  Secondary:   Perceived Hot Flash Interference (Hot Flash Related Daily Interference Scale; HFRDIS) -- Week 4   [ Time Frame: Week 4 ]

8.  Secondary:   Perceived Hot Flash Interference (Hot Flash Related Daily Interference Scale; HFRDIS) -- Week 8   [ Time Frame: Week 8 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Findings may be specific to the particular dose of each agent used, treatment period, as well as the preparation and oral administration of estrogen therapy.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Hadine Joffe, MD, MSc
Organization: Brigham and Women's Hospital
phone: 617-732-4906
e-mail: hjoffe@partners.org


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):


Responsible Party: Katherine Guthrie, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01418209     History of Changes
Other Study ID Numbers: MsFLASH-03
1U01AG032700-01 ( U.S. NIH Grant/Contract )
1U01AG032699-01 ( U.S. NIH Grant/Contract )
Study First Received: August 15, 2011
Results First Received: June 18, 2014
Last Updated: August 20, 2014