Trial Outcomes & Findings for Gabapentin for Insomnia Symptoms and Nighttime Vasomotor Symptoms (VMS) in Peri- and Postmenopausal Women (NCT NCT02040532)

NCT ID: NCT02040532

Last Updated: 2019-08-07

Results Overview

Tolerability of gabapentin was assessed by self-report at the week 1, week 4 and week 7 contacts by asking participants to complete the SAFTEE-SI and CPFQ questionnaires and prompting subjects to report any adverse events at each study visit. Tolerability of gabapentin is defined as the proportion of participants that is able to increase the dose from 300-mg to 600-mg and to remain on the higher dose for the duration of the trial.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

32 participants

Primary outcome timeframe

Baseline, Week 4 visit, and study completion at 7 weeks

Results posted on

2019-08-07

Participant Flow

Women were recruited from the Boston area and enrolled at either the Massachusetts General Hospital Center for Women's Mental Health or the Brigham and Women's Hospital Women's Hormones and Aging Research Program.

Participant milestones

Participant milestones
Measure
Open-label Gabapentin
Dose titration of 100mg for 1 week, 300mg for 3 weeks, and 600mg for 3 weeks. Gabapentin: The study is a 7-week intervention study using open-label gabapentin at bedtime with a scheduled dose titration from 100-mg for one week, followed by 300-mg for 3 weeks, and then 600-mg for 3 weeks.
Overall Study
STARTED
32
Overall Study
Received at Least One Dose of Medication
26
Overall Study
COMPLETED
20
Overall Study
NOT COMPLETED
12

Reasons for withdrawal

Reasons for withdrawal
Measure
Open-label Gabapentin
Dose titration of 100mg for 1 week, 300mg for 3 weeks, and 600mg for 3 weeks. Gabapentin: The study is a 7-week intervention study using open-label gabapentin at bedtime with a scheduled dose titration from 100-mg for one week, followed by 300-mg for 3 weeks, and then 600-mg for 3 weeks.
Overall Study
Lost to Follow-up
1
Overall Study
Physician Decision
4
Overall Study
Adverse Event
4
Overall Study
Withdrawal by Subject
3

Baseline Characteristics

Gabapentin for Insomnia Symptoms and Nighttime Vasomotor Symptoms (VMS) in Peri- and Postmenopausal Women

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Open-label Gabapentin
n=26 Participants
Dose titration of 100mg for 1 week, 300mg for 3 weeks, and 600mg for 3 weeks. Gabapentin: The study is a 7-week intervention study using open-label gabapentin at bedtime with a scheduled dose titration from 100-mg for one week, followed by 300-mg for 3 weeks, and then 600-mg for 3 weeks.
Age, Continuous
55.31 years
STANDARD_DEVIATION 4.5 • n=5 Participants
Sex: Female, Male
Female
26 Participants
n=5 Participants
Sex: Female, Male
Male
0 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
2 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
24 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
10 Participants
n=5 Participants
Race (NIH/OMB)
White
16 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Region of Enrollment
United States
26 Participants
n=5 Participants
Highest Level of Education
Less than College Graduate
18 Participants
n=5 Participants
Highest Level of Education
College Graduate/Baccalaureate Degree
4 Participants
n=5 Participants
Highest Level of Education
Graduate Degree
4 Participants
n=5 Participants
Employment
Employed Full-Time
8 Participants
n=5 Participants
Employment
Employed Part-Time
6 Participants
n=5 Participants
Employment
Retired or Unemployed
8 Participants
n=5 Participants
Employment
Disabled, Unable to work, on Medical Leave
4 Participants
n=5 Participants
Marital Status
Never Married
7 Participants
n=5 Participants
Marital Status
Divorced or Separated
5 Participants
n=5 Participants
Marital Status
Widowed
2 Participants
n=5 Participants
Marital Status
Presently Married or Living with Partner
12 Participants
n=5 Participants
Gynecological History
Perimenopausal
5 Participants
n=5 Participants
Gynecological History
Naturally Postmenopausal
18 Participants
n=5 Participants
Gynecological History
Surgically Postmenopausal
3 Participants
n=5 Participants
Years since last menstrual period (LMP)
<1 Years
5 Participants
n=5 Participants
Years since last menstrual period (LMP)
1-5 Years
13 Participants
n=5 Participants
Years since last menstrual period (LMP)
>5 Years
8 Participants
n=5 Participants
Number of Children
No Children
12 Participants
n=5 Participants
Number of Children
1 to 4 Children
14 Participants
n=5 Participants
Smoking History
Current Smoker
4 Participants
n=5 Participants
Smoking History
Non-Current Smoker
22 Participants
n=5 Participants
Baseline BMI
29.4 kg/m^2
STANDARD_DEVIATION 6.6 • n=5 Participants
Provider Status
Has Doctor/Nurse Providing Regular Care
25 Participants
n=5 Participants
Provider Status
Does not have Doctor/Nurse Providing Regular Care
1 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 4 visit, and study completion at 7 weeks

Population: All 26 participants who initiated treatment with gabapentin were included in this analysis.

Tolerability of gabapentin was assessed by self-report at the week 1, week 4 and week 7 contacts by asking participants to complete the SAFTEE-SI and CPFQ questionnaires and prompting subjects to report any adverse events at each study visit. Tolerability of gabapentin is defined as the proportion of participants that is able to increase the dose from 300-mg to 600-mg and to remain on the higher dose for the duration of the trial.

Outcome measures

Outcome measures
Measure
Open-label Gabapentin
n=26 Participants
Dose titration of 100mg for 1 week, 300mg for 3 weeks, and 600mg for 3 weeks. Gabapentin: The study is a 7-week intervention study using open-label gabapentin at bedtime with a scheduled dose titration from 100-mg for one week, followed by 300-mg for 3 weeks, and then 600-mg for 3 weeks.
Tolerability of Gabapentin
# of subjects who tolerated gabapentin
22 Participants
Tolerability of Gabapentin
# of subjects who did not tolerate gabapentin
4 Participants

PRIMARY outcome

Timeframe: Baseline, Week 4 Visit, and study completion at 7 weeks

Population: Four subjects initiated treatment with gabapentin but discontinued prior to study completion due to side effects.

Reason why subjects who initiated treatment with gabapentin chose to discontinue before study completion

Outcome measures

Outcome measures
Measure
Open-label Gabapentin
n=4 Participants
Dose titration of 100mg for 1 week, 300mg for 3 weeks, and 600mg for 3 weeks. Gabapentin: The study is a 7-week intervention study using open-label gabapentin at bedtime with a scheduled dose titration from 100-mg for one week, followed by 300-mg for 3 weeks, and then 600-mg for 3 weeks.
Reason for Non-tolerability and Discontinuation of Gabapentin
Morning sickness and Nausea
3 Participants
Reason for Non-tolerability and Discontinuation of Gabapentin
Mild Rash
1 Participants

PRIMARY outcome

Timeframe: Baseline, study completion at 7 weeks

Population: Though 20 participants completed the study, the analyzable population includes only the 19 completers who have VMS data for both baseline and the final visit.

Vasomotor symptoms (VMS) were tracked and quantified prospectively using a daily hot flash diary. The hot flash diary was adapted from a 7-day self-report tool for vasomotor symptoms originally developed by the North Central Cancer Treatment Group (NCCTG). The diary asks for the subject to log number of hot flashes during the day and night, severity of hot flashes during day and night, and how bothersome the hot flashes were during day and night. Vasomotor symptoms were also systematically assessed at baseline, week 4, and week 7 using the Hot Flash-Related Daily Interference Scale (HFRDIS), a 10-item self-report questionnaire to determine perceived hot flash interference with quality of life and daily activities.

Outcome measures

Outcome measures
Measure
Open-label Gabapentin
n=19 Participants
Dose titration of 100mg for 1 week, 300mg for 3 weeks, and 600mg for 3 weeks. Gabapentin: The study is a 7-week intervention study using open-label gabapentin at bedtime with a scheduled dose titration from 100-mg for one week, followed by 300-mg for 3 weeks, and then 600-mg for 3 weeks.
Vasomotor Symptoms (VMS) Frequency, Severity, and Bothersomeness During Daytime
mean VMS per day at baseline
4.1 vasomotor symptoms (VMS) per day
Interval 0.2 to 8.5
Vasomotor Symptoms (VMS) Frequency, Severity, and Bothersomeness During Daytime
mean VMS per day at study completion
2.2 vasomotor symptoms (VMS) per day
Interval 0.0 to 6.7

PRIMARY outcome

Timeframe: Baseline, study completion at 7 weeks

Population: Though 20 participants completed the study, the analyzable population includes only the 19 completers who have VMS data for both baseline and the final visit.

Vasomotor symptoms (VMS) were tracked and quantified prospectively using a daily hot flash diary. The hot flash diary was adapted from a 7-day self-report tool for vasomotor symptoms originally developed by the North Central Cancer Treatment Group (NCCTG). The diary asks for the subject to log number of hot flashes during the day and night, severity of hot flashes during day and night, and how bothersome the hot flashes were during day and night. Vasomotor symptoms were also systematically assessed at baseline, week 4, and week 7 using the Hot Flash-Related Daily Interference Scale (HFRDIS), a 10-item self-report questionnaire to determine perceived hot flash interference with quality of life and daily activities.

Outcome measures

Outcome measures
Measure
Open-label Gabapentin
n=19 Participants
Dose titration of 100mg for 1 week, 300mg for 3 weeks, and 600mg for 3 weeks. Gabapentin: The study is a 7-week intervention study using open-label gabapentin at bedtime with a scheduled dose titration from 100-mg for one week, followed by 300-mg for 3 weeks, and then 600-mg for 3 weeks.
Vasomotor Symptoms (VMS) Frequency, Severity, and Bothersomeness During Nighttime
mean VMS per night at baseline
3.5 vasomotor symptoms (VMS) per night
Interval 1.5 to 8.0
Vasomotor Symptoms (VMS) Frequency, Severity, and Bothersomeness During Nighttime
mean VMS per night at study completion
1.1 vasomotor symptoms (VMS) per night
Interval 0.0 to 3.9

PRIMARY outcome

Timeframe: Baseline, study completion at 7 weeks

Population: Analyzable population includes all 20 completers of the study, since all 20 completers of the study had ISI data at baseline and study completion.

Severity of insomnia was measured throughout the study using the Insomnia Severity Index (ISI) .The ISI is a 7-item scale that evaluates the severity of insomnia retrospectively over the past week. The scale is more specific to insomnia symptoms than the Pittsburgh scale (PSQI), which focuses more broadly on overall sleep quality. The ISI score ranges from a minimum of 0 to 28. A score of 0-7=no clinically significant insomnia, 8-14=subthreshold insomnia, 5-21=clinical insomnia (moderate severity), 22-28=clinical insomnia (severe), with higher values indicating more severe insomnia.

Outcome measures

Outcome measures
Measure
Open-label Gabapentin
n=20 Participants
Dose titration of 100mg for 1 week, 300mg for 3 weeks, and 600mg for 3 weeks. Gabapentin: The study is a 7-week intervention study using open-label gabapentin at bedtime with a scheduled dose titration from 100-mg for one week, followed by 300-mg for 3 weeks, and then 600-mg for 3 weeks.
Severity of Insomnia
mean ISI score at baseline
15.6 scores on a scale
Interval 8.0 to 24.0
Severity of Insomnia
mean ISI score at study completion
6.0 scores on a scale
Interval 0.0 to 18.0

PRIMARY outcome

Timeframe: Baseline, study completion at 7 weeks

Population: Analyzable population includes all 20 completers of the study, since all 20 completers of the study had PSQI data at baseline and study completion.

Sleep quality and disturbances during the past month were assessed with the Pittsburgh Sleep Quality Index (PSQI). The PSQI also incorporates daytime functioning into the total score. In scoring the PSQI, seven component scores are derived, each scored 0 (no difficulty) to 3 (severe difficulty). The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality.

Outcome measures

Outcome measures
Measure
Open-label Gabapentin
n=20 Participants
Dose titration of 100mg for 1 week, 300mg for 3 weeks, and 600mg for 3 weeks. Gabapentin: The study is a 7-week intervention study using open-label gabapentin at bedtime with a scheduled dose titration from 100-mg for one week, followed by 300-mg for 3 weeks, and then 600-mg for 3 weeks.
Sleep Quality and Disturbances Over Past Month
PSQI total score at baseline
9.6 scores on a scale
Interval 4.0 to 17.0
Sleep Quality and Disturbances Over Past Month
PSQI total score at study completion
4.9 scores on a scale
Interval 0.0 to 12.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, study completion at 7 weeks

Population: Analyzable population includes all 20 completers of the study, since all 20 completers of the study had Q-LES-Q data at baseline and study completion.

Quality of life-Overall was assessed with the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). The Q-LES-Q is a 16-item self-report questionnaire that assesses enjoyment of and satisfaction with life. The scoring of the Q-LES-Q-SF involves summing only the first 14 items to yield a raw total score. The last two items are not included in the total score but are standalone items. The raw total score ranges from 14 to 70 with higher scores indicating higher quality of life enjoyment and satisfaction.

Outcome measures

Outcome measures
Measure
Open-label Gabapentin
n=20 Participants
Dose titration of 100mg for 1 week, 300mg for 3 weeks, and 600mg for 3 weeks. Gabapentin: The study is a 7-week intervention study using open-label gabapentin at bedtime with a scheduled dose titration from 100-mg for one week, followed by 300-mg for 3 weeks, and then 600-mg for 3 weeks.
Quality of Life-Overall
Q-LES-Q scores at baseline
60.3 scores on a scale
Interval 30.0 to 80.0
Quality of Life-Overall
Q-LES-Q scores at study completion
61.7 scores on a scale
Interval 35.0 to 80.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, study completion at 7 weeks

Population: Analyzable population includes all 20 completers of the study, since all 20 completers of the study had MENQOL data at baseline and study completion.

The Quality of life-Menopause specific is assessed by the Menopause Specific Quality of Life (MENQOL). The MENQOL is self-administered and consists of a total of 29 items in a Likert-scale format. Each item assesses the impact of one of four domains of menopausal symptoms, as experienced over the last month: vasomotor (items 1-3), psychosocial (items 4-10), physical (items 11-26), and sexual (items 27-29). Items pertaining to a specific symptom are rated as present or not present, and if present, how bothersome on a zero (not bothersome) to six (extremely bothersome) scale. Means are computed for each subscale by dividing the sum of the domain's items by the number of items within that domain. Non-endorsement of an item is scored a "1" and endorsement a "2," plus the number of the particular rating, so that the possible score on any item ranges from 1-8. Total score also ranges from 1-8.

Outcome measures

Outcome measures
Measure
Open-label Gabapentin
n=20 Participants
Dose titration of 100mg for 1 week, 300mg for 3 weeks, and 600mg for 3 weeks. Gabapentin: The study is a 7-week intervention study using open-label gabapentin at bedtime with a scheduled dose titration from 100-mg for one week, followed by 300-mg for 3 weeks, and then 600-mg for 3 weeks.
Quality of Life-Menopause Specific
MENQOL scores at baseline
3.2 scores on a scale
Interval 1.0 to 5.0
Quality of Life-Menopause Specific
MENQOL scores at study completion
1.9 scores on a scale
Interval 1.0 to 3.5

Adverse Events

Open-label Gabapentin

Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Open-label Gabapentin
n=26 participants at risk
Dose titration of 100mg for 1 week, 300mg for 3 weeks, and 600mg for 3 weeks. Gabapentin: The study is a 7-week intervention study using open-label gabapentin at bedtime with a scheduled dose titration from 100-mg for one week, followed by 300-mg for 3 weeks, and then 600-mg for 3 weeks.
Nervous system disorders
Headaches
34.6%
9/26 • Adverse event data was collected using the SAFTEE-SI self-report questionnaire at each visit
Respiratory, thoracic and mediastinal disorders
Sweating
30.8%
8/26 • Adverse event data was collected using the SAFTEE-SI self-report questionnaire at each visit
Pregnancy, puerperium and perinatal conditions
Hot flashes
26.9%
7/26 • Adverse event data was collected using the SAFTEE-SI self-report questionnaire at each visit
Respiratory, thoracic and mediastinal disorders
Nasal congestion
23.1%
6/26 • Adverse event data was collected using the SAFTEE-SI self-report questionnaire at each visit
General disorders
Feeling tired/fatigue
23.1%
6/26 • Adverse event data was collected using the SAFTEE-SI self-report questionnaire at each visit
General disorders
Feeling drowsy during the day
30.8%
8/26 • Adverse event data was collected using the SAFTEE-SI self-report questionnaire at each visit
General disorders
Problems falling asleep
15.4%
4/26 • Adverse event data was collected using the SAFTEE-SI self-report questionnaire at each visit
Metabolism and nutrition disorders
Weight gain
15.4%
4/26 • Adverse event data was collected using the SAFTEE-SI self-report questionnaire at each visit
Gastrointestinal disorders
Stomach/abdominal discomfort
15.4%
4/26 • Adverse event data was collected using the SAFTEE-SI self-report questionnaire at each visit
Gastrointestinal disorders
Gas
15.4%
4/26 • Adverse event data was collected using the SAFTEE-SI self-report questionnaire at each visit
Psychiatric disorders
Tension
15.4%
4/26 • Adverse event data was collected using the SAFTEE-SI self-report questionnaire at each visit
Reproductive system and breast disorders
Increased interest in sex
15.4%
4/26 • Adverse event data was collected using the SAFTEE-SI self-report questionnaire at each visit
General disorders
Waking up too early
15.4%
4/26 • Adverse event data was collected using the SAFTEE-SI self-report questionnaire at each visit
Respiratory, thoracic and mediastinal disorders
Coughing
15.4%
4/26 • Adverse event data was collected using the SAFTEE-SI self-report questionnaire at each visit
Musculoskeletal and connective tissue disorders
Aches, pains in muscles, bones or joints
15.4%
4/26 • Adverse event data was collected using the SAFTEE-SI self-report questionnaire at each visit
General disorders
Nausea
11.5%
3/26 • Adverse event data was collected using the SAFTEE-SI self-report questionnaire at each visit
Skin and subcutaneous tissue disorders
Mild rash
3.8%
1/26 • Adverse event data was collected using the SAFTEE-SI self-report questionnaire at each visit

Additional Information

Dr. Lee Cohen

MGH Center for Women's Mental Health

Phone: 617-724-0816

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place