Hot Flushes
Conditions
Keywords
menopause, hot flashes, vilazodone
Brief summary
This is a pilot study to determine proof in principle that vilazodone, a selective serotonin reuptake inhibitor and 5HT1a agonist, reduces the frequency and severity of menopausal hot flashes relative to placebo. A secondary aim is to evaluate improvement in menopause-related quality of life.
Detailed description
This is a proposal to conduct a small clinical trial for proof in principle that vilazodone reduces the frequency and severity of menopausal hot flashes. An additional exploratory aim is to identify improvement in menopause-related quality of life. Healthy, perimenopausal women ages 45-60 with an average of 4 or more moderate or severe hot flashes/night sweats per day for 3 screening weeks will be randomized to 8 weeks of treatment in a 2:1 ratio of vilazodone or matching placebo pills. Flexible dosing of vilazodone will start at 10 mg once/day for 7 days, increase to 20 mg/day for 1 more week and increase to 40 mg once/day at week 3 if unimproved. The primary outcome assessments are the frequency and severity of hot flashes at week 4 and week 8 as assessed by prospective daily diaries (using 7-day mean scores from the daily diaries). The secondary outcome is clinical improvement, defined as hot flash frequency \>=50% decrease from baseline. Treatment-emergent adverse events will be monitored and patient ratings of tolerability will be obtained.
Interventions
DRUGvilazodone
capsules once/day for 8 weeks. Dose starts at 10 mg for 7 days, increases to 20 mg/day for 7 days, increases to 40 mg/day at week 3 of unimproved.
DRUGplacebo capsules
placebo capsules matched to drug capsules.
Sponsors
Forest Laboratories
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Women ages 45-60 years * Amenorrhea for 60 days or more or postmenopausal or bi-lateral oophorectomy. * 4 or more moderate or severe hot flashes or night sweats per 24 hour period (28/week) as recorded on daily diaries in 3 screening weeks. * Hot flashes/night sweats rated as moderate to severe and/or bothersome (moderately to a lot) on 4 or more days/nights in each screen week. * In general good health. * Signed informed consent.
Exclusion criteria
* Psychotropic medications currently or within the last 30 days. * Current use of hormonal medications such as hormone therapy or hormonal contraception or any treatment for hot flashes (Prescription, over-the-counter or herbal). * Drug or alcohol abuse in the past year. * Lifetime diagnosis of psychosis or bipolar disorder. * Suicide attempt in the past 3 years or any current suicidal ideation. * Current major depression. * Not using a medically approved, non-hormonal method of birth control if sexually active and not postmenopausal (12 or more months since last menstrual period or bi-lateral oophorectomy). * Pregnancy, intending pregnancy or breast feeding. * Any severe of unstable medical illness, e.g., breast or ovarian cancer, seizure disorders, etc. * Current participation in another intervention study. * Inability or unwillingness to complete study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Daily Diary Ratings of Severity of Hot Flashes | Week 8. | Hot flash severity will be recorded daily in the am and pm on a scale of 0 (none) to 3 (severe). The frequency of hot flashes was the number reported. The severity of hot flashes was rated on a scale of 0 (none) to 3 (severe). 7-day averages were calculated for baseline, week 4 and week 8 and a mean daily score was obtained for analysis. Baseline values were the means of the first 2 screen weeks. Possible range of the severity scale for the daily mean was 0 (none) to 3 (severe). |
| Daily Diary Ratings of Frequency of Hot Flashes | Week 8. | Hot flash frequency and severity will be recorded daily in the am and pm on a scale of 0 (none) to 3 (severe). The frequency of hot flashes was the number reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Patients With >=50% Reduction in Moderate to Severe Hot Flashes | Percent change from baseline at Week 8 | Percent of patients with n \>=50% reduction in frequency of moderate to severe hot flashes calculated from daily diaries |
| Menopause-related Quality of Life (MENQOL) | Week 8 | The MENQOL is a validated measure to assess the presence and bother of menopausal symptoms. This will be exploratory. Each of 29 items is rated on a scale of 0 to 6 (extremely bothersome). The items are divided into 4 subscales. The item scores are summed in each subscale and means are computed for the 4 subscales. The total score is the sum of the mean subscale scores. Higher scores are more symptomatic. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants That Were Satisfied or Very Satisfied | Week 8 | Patient global rating of satisfaction with medication reported on a scale of 0 to 5 (very satisfied). |
| Number of Participants With Adverse Events | Baseline and Week 12 | A 17 item checklist of general adverse and withdrawal symptoms. It will be used at baseline and Week 12. Adverse events will be obtained by subject report at Week 4 and Week 8. |
| Sheehan Global Ratings of Symptom (Hot Flash)Interference | Change from Baseline at Week 8 | Global ratings on a 10-point scale of the degree that symptoms interfere overall, with work, social activities and family life. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Experimental 1 vilazodone (viibryd). 20 mg or 40 mg/day for 8 weeks
vilazodone: capsules once/day for 8 weeks. Dose starts at 10 mg for 7 days, increases to 20 mg/day for 7 days, increases to 40 mg/day at week 3 of unimproved. | 24 |
| Placebo Capsules (Sugar Pill) Placebo capsules matched to the drug dose for 8 weeks
placebo capsules: placebo capsules matched to drug capsules. | 12 |
| Total | 36 |
Baseline characteristics
| Characteristic | Experimental 1 | Placebo Capsules (Sugar Pill) | Total |
|---|---|---|---|
| Age, Continuous | 51.5 years STANDARD_DEVIATION 3.7 | 52.7 years STANDARD_DEVIATION 4.2 | 51.9 years STANDARD_DEVIATION 3.9 |
| Region of Enrollment United States | 24 participants | 12 participants | 36 participants |
| Sex: Female, Male Female | 24 Participants | 12 Participants | 36 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 17 / 24 | 6 / 12 |
| serious Total, serious adverse events | 0 / 24 | 0 / 12 |
Outcome results
Primary
Daily Diary Ratings of Frequency of Hot Flashes
Hot flash frequency and severity will be recorded daily in the am and pm on a scale of 0 (none) to 3 (severe). The frequency of hot flashes was the number reported.
Time frame: Week 8.
Population: all participants randomized to treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Experimental 1 | Daily Diary Ratings of Frequency of Hot Flashes | 3.65 number of hot flashes |
| Placebo Capsules (Sugar Pill) | Daily Diary Ratings of Frequency of Hot Flashes | 4.71 number of hot flashes |
p-value: 0.0595% CI: [-2.6, -0.48]Regression, Linear
Primary
Daily Diary Ratings of Severity of Hot Flashes
Hot flash severity will be recorded daily in the am and pm on a scale of 0 (none) to 3 (severe). The frequency of hot flashes was the number reported. The severity of hot flashes was rated on a scale of 0 (none) to 3 (severe). 7-day averages were calculated for baseline, week 4 and week 8 and a mean daily score was obtained for analysis. Baseline values were the means of the first 2 screen weeks. Possible range of the severity scale for the daily mean was 0 (none) to 3 (severe).
Time frame: Week 8.
Population: all participants randomized to treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Experimental 1 | Daily Diary Ratings of Severity of Hot Flashes | 1.17 units on a scale |
| Placebo Capsules (Sugar Pill) | Daily Diary Ratings of Severity of Hot Flashes | 1.39 units on a scale |
p-value: 0.0595% CI: [-0.74, -0.21]Regression, Linear
Secondary
Menopause-related Quality of Life (MENQOL)
The MENQOL is a validated measure to assess the presence and bother of menopausal symptoms. This will be exploratory. Each of 29 items is rated on a scale of 0 to 6 (extremely bothersome). The items are divided into 4 subscales. The item scores are summed in each subscale and means are computed for the 4 subscales. The total score is the sum of the mean subscale scores. Higher scores are more symptomatic.
Time frame: Week 8
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Experimental 1 | Menopause-related Quality of Life (MENQOL) | 1.89 units on a scale |
| Placebo Capsules (Sugar Pill) | Menopause-related Quality of Life (MENQOL) | 2.08 units on a scale |
p-value: <0.0595% CI: [-0.75, -0.08]Regression, Linear
Secondary
Percent of Patients With >=50% Reduction in Moderate to Severe Hot Flashes
Percent of patients with n \>=50% reduction in frequency of moderate to severe hot flashes calculated from daily diaries
Time frame: Percent change from baseline at Week 8
Population: all participants with at least one treatment response
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental 1 | Percent of Patients With >=50% Reduction in Moderate to Severe Hot Flashes | 65 percentage of participants |
| Placebo Capsules (Sugar Pill) | Percent of Patients With >=50% Reduction in Moderate to Severe Hot Flashes | 83 percentage of participants |
p-value: <0.05Chi-squared
Other Pre-specified
Number of Participants With Adverse Events
A 17 item checklist of general adverse and withdrawal symptoms. It will be used at baseline and Week 12. Adverse events will be obtained by subject report at Week 4 and Week 8.
Time frame: Baseline and Week 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental 1 | Number of Participants With Adverse Events | 17 participants |
| Placebo Capsules (Sugar Pill) | Number of Participants With Adverse Events | 6 participants |
Other Pre-specified
Percentage of Participants That Were Satisfied or Very Satisfied
Patient global rating of satisfaction with medication reported on a scale of 0 to 5 (very satisfied).
Time frame: Week 8
Population: all participants with at least one treatment response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental 1 | Percentage of Participants That Were Satisfied or Very Satisfied | 65 percentage of participants |
| Placebo Capsules (Sugar Pill) | Percentage of Participants That Were Satisfied or Very Satisfied | 75 percentage of participants |
Other Pre-specified
Sheehan Global Ratings of Symptom (Hot Flash)Interference
Global ratings on a 10-point scale of the degree that symptoms interfere overall, with work, social activities and family life.
Time frame: Change from Baseline at Week 8