Menopause
Conditions
Keywords
fatigue, menopausal symptoms, hot flashes, Vasomotor symptoms, perimenopause, related Quality of life
Brief summary
The purpose of this study is to determine if armodafinil improves quality of life and is an effective treatment of fatigue in symptomatic perimenopausal and postmenopausal women.
Detailed description
Fatigue is one of the most prevalent symptoms occurring in peri- and postmenopausal women. It is strongly associated with reduced quality of life in this population. Studies have shown a strong association between fatigue and menopausal symptoms such as hot flashes, vaginal symptoms, and sexual dysfunction. Because sleep disturbance commonly co-occurs in women with hot flashes as a result of nocturnal hot flashes disrupting sleep, sleep disturbance may explain the association between hot flashes and fatigue in this population. However evidence suggests that fatigue can occur in the absence of sleep disruption, indicating that sleep problems do not exclusively explain the etiology of fatigue in this population. Armodafinil is a wakefulness-promoting agent that acts as a central nervous system stimulant. It is chemically and pharmacologically unrelated to other CNS stimulants, such as methylphenidate and amphetamine. Armodafinil is FDA approved to increase wakefulness in patients with excessive sleepiness due to narcolepsy, obstructive sleep apnea, and shift work sleep disorder. It has not be studied in menopause-associated fatigue. In the proposed study, the investigators plan to investigate the effect of armodafinil on quality of life and fatigue in a population of peri- and postmenopausal women with fatigue and reduced quality of life who do not have primary sleep disorders, significant levels of insomnia, or depression.
Interventions
DRUGArmodafinil
Women who are eligible will receive 4 weeks of treatment with armodafinil. Armodafinil will be titrated from 50-mg/day up to 150-mg/day. For exploratory reasons only, at the end of the 4-week treatment period, participants will enter a discontinuation phase in which they will be randomized to double-blind treatment with armodafinil 150-mg/day or matching placebo for 2 weeks in a 1-to-1 ratio. No primary outcomes were studied in the discontinuation phase.
Sponsors
Teva Pharmaceuticals USA
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Women * Ages 40-65 * Peri- and postmenopausal * Suffering from fatigue * Experiencing hot flashes(Not required for perimenopausal women)
Exclusion criteria
* Current episode of major depression * Moderate-to-severe insomnia * Night shift workers * Previous diagnosis of manic depressive disorder, psychotic disorder, or psychotic symptoms * Suicidal ideation * Alcohol/drug abuse * Concern about potential misuse of study medication * Use of prescribed medications to treat insomnia or other sleep disturbance symptoms * Pregnant or breastfeeding * Use of systemic menopausal hormonal therapy or birth control * Use of centrally active medications, such as antidepressants, anxiolytics, and hypnotics agents * Use of clopidogrel * Use of atomoxetine * Cardiovascular contraindications of use of armodafinil
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Menopause Quality Of Life Questionnaire (MENQOL) Physical Domain Subscale | 4 weeks | This is a widely used self-report instrument to determine differences in quality of life among menopausal women and to measure changes in their quality of life over time. Four domain scores are calculated from the 29-item instrument. The physical domain subscale has 16 questions and a range from 0-8 with higher scores indicating worse symptoms. |
| Brief Fatigue Inventory (BFI) | 4 weeks | This is a widely used self-report instrument to assess the severity of fatigue and the impact of fatigue on daily functioning. This 9 item instrument yields a global fatigue score ranging from 0-10 with higher scores indicating worse symptoms. . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Symptom Checklist-10 Anxiety | 4 weeks | The SCL-10 anxiety subscale, developed from the refinement of the Hopkins Symptom Checklist (HSCL), consists of 10 questions focused on how much discomfort symptoms of anxiety (e.g. nervousness or shaking inside) have caused in the past two weeks. Each question is answered on a scale from 0-4, and answers are averaged for a total score between 0-4 with higher scores indicating more anxiety. |
| Epsworth Sleepiness Scale (ESS) | 4 weeks | This self-report scale is widely used as a subjective measure of sleepiness. This 8 item instrument yields a total score ranging from 0-24 with higher scores indicating worse symptoms. |
| Brown Attention Deficit Disorder Scale (BADDS) | 4 weeks | This is a normed and validated measure of ADHD-related executive function impairments. The clinician administered scale measures five clusters of executive function including 1) organizing and activating for work, 2) sustaining attention and concentration, 3) sustaining alertness, effort, and processing speed, 4) managing affective interference, and 5) using working memory and accessing recall. The frequency and severity of each of the 40 items is rated on a scale of 0 to 3, with the total scores ranging from 0-120 and higher scores indicating worse symptoms. |
| Patient Health Questionnaire-9 (PHQ-9) | 4 weeks | The PHQ-9 is the self-administered form of the Primary Care Evaluation of Mental Disorders (PRIME-MD), a widely used instrument designed to screen for psychiatric illnesses in primary-care settings. This 9-item instrument assesses mood, depressive symptoms, and suicidal ideation. The range of total scores is 0-27 with higher scores indicating worse symptoms. Generally, scores 5-9 indicate mild depression, 10-14 indicate moderate depression, and 15+ indicate moderately severe or severe depression. |
| Hot Flash Frequency (24-hr Period) | 4 weeks | The Daily Vasomotor Symptom Diary consists of a 7-day scale on which the subject records the total number of hot flushes they experience on a daily basis. Weekly averages for a 24-hour period are calculated. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Armodafinil Armodafinil is the drug being tested. Women who are eligible will receive 4 weeks of treatment with armodafinil. Armodafinil will be titrated from 50-mg/day up to 150-mg/day. For exploratory reasons only, at the end of the 4-week treatment period, participants will enter a discontinuation phase in which they will be randomized to double-blind treatment with armodafinil 150-mg/day or matching placebo for 2 weeks in a 1-to-1 ratio. | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Armodafinil |
|---|---|
| Age, Continuous | 53.8 years STANDARD_DEVIATION 5.13 |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 16 / 25 |
| serious Total, serious adverse events | 0 / 25 |
Outcome results
Primary
Brief Fatigue Inventory (BFI)
This is a widely used self-report instrument to assess the severity of fatigue and the impact of fatigue on daily functioning. This 9 item instrument yields a global fatigue score ranging from 0-10 with higher scores indicating worse symptoms. .
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Armodafinil | Brief Fatigue Inventory (BFI) | 2.2 units on a scale |
Primary
Menopause Quality Of Life Questionnaire (MENQOL) Physical Domain Subscale
This is a widely used self-report instrument to determine differences in quality of life among menopausal women and to measure changes in their quality of life over time. Four domain scores are calculated from the 29-item instrument. The physical domain subscale has 16 questions and a range from 0-8 with higher scores indicating worse symptoms.
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Armodafinil | Menopause Quality Of Life Questionnaire (MENQOL) Physical Domain Subscale | 1.9 units on a scale |
Secondary
Brown Attention Deficit Disorder Scale (BADDS)
This is a normed and validated measure of ADHD-related executive function impairments. The clinician administered scale measures five clusters of executive function including 1) organizing and activating for work, 2) sustaining attention and concentration, 3) sustaining alertness, effort, and processing speed, 4) managing affective interference, and 5) using working memory and accessing recall. The frequency and severity of each of the 40 items is rated on a scale of 0 to 3, with the total scores ranging from 0-120 and higher scores indicating worse symptoms.
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Armodafinil | Brown Attention Deficit Disorder Scale (BADDS) | 15.5 units on a scale |
Secondary
Epsworth Sleepiness Scale (ESS)
This self-report scale is widely used as a subjective measure of sleepiness. This 8 item instrument yields a total score ranging from 0-24 with higher scores indicating worse symptoms.
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Armodafinil | Epsworth Sleepiness Scale (ESS) | 3.0 units on a scale |
Secondary
Hot Flash Frequency (24-hr Period)
The Daily Vasomotor Symptom Diary consists of a 7-day scale on which the subject records the total number of hot flushes they experience on a daily basis. Weekly averages for a 24-hour period are calculated.
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Armodafinil | Hot Flash Frequency (24-hr Period) | 1.5 # of hot flashes |
Secondary
Patient Health Questionnaire-9 (PHQ-9)
The PHQ-9 is the self-administered form of the Primary Care Evaluation of Mental Disorders (PRIME-MD), a widely used instrument designed to screen for psychiatric illnesses in primary-care settings. This 9-item instrument assesses mood, depressive symptoms, and suicidal ideation. The range of total scores is 0-27 with higher scores indicating worse symptoms. Generally, scores 5-9 indicate mild depression, 10-14 indicate moderate depression, and 15+ indicate moderately severe or severe depression.
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Armodafinil | Patient Health Questionnaire-9 (PHQ-9) | 3.0 units on a scale |
Secondary
Symptom Checklist-10 Anxiety
The SCL-10 anxiety subscale, developed from the refinement of the Hopkins Symptom Checklist (HSCL), consists of 10 questions focused on how much discomfort symptoms of anxiety (e.g. nervousness or shaking inside) have caused in the past two weeks. Each question is answered on a scale from 0-4, and answers are averaged for a total score between 0-4 with higher scores indicating more anxiety.
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Armodafinil | Symptom Checklist-10 Anxiety | 0 units on a scale |