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

Study Overview
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Brief Summary
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The broad goal of this study is to obtain pilot data to determine the tolerability and preliminary efficacy of the non-hormonal agent gabapentin for insomnia symptoms and nighttime vasomotor Symptoms (VMS) when open-label gabapentin is administered at low dose and only at night in peri- and postmenopausal women. We hypothesize that the majority of participants will be able to increase and tolerate treatment, and insomnia symptoms and the frequency of nighttime VMS will improve on low-dose gabapentin dosed at bedtime.

Detailed Description
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Thirty-two peri- and postmenopausal women at the Boston sites (MGH and BWH) were enrolled into this open-label pilot study. The study was 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. The intervention study followed a 3-week screening period to establish a stable baseline for insomnia symptoms and VMS and to determine the safety of administering gabapentin in study participants. Tolerability and treatment response (insomnia symptoms, nighttime VMS) were assessed systematically at each study visit. The dose titration schedule was followed in all participants unless there are dose-limiting toxicities.

Official Title
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Pilot Study to Assess Tolerability and Preliminary Efficacy of a Titrated Dose of Gabapentin up to 600mg Administered at Bedtime for Insomnia Symptoms and Nighttime Vasomotor Symptoms (VMS) in Peri- and Postmenopausal Women With VMS.

Conditions
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Menopause, Hot Flashes, Vasomotor Disturbance

Intervention / Treatment
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* Drug: Gabapentin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females aged 40-65 years Postmenopausal or perimenopausal Having bothersome hot flashes Having some bothersome hot flashes during the night Insomnia or problems sleeping In general, good health Signed informed consent Exclusion Criteria: Recent use of hormone therapy or hormonal contraceptives (with the exception of the Mirena IUD) Recent use of any prescribed therapy that is taken specifically for hot flashes Recent use of any over-the-counter or herbal therapies that are taken specifically for hot flashes Recent use of any prescribed medications with known hot flash efficacy Known hypersensitivity or contraindications (reasons not to take) to gabapentin 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: Renal insufficiency or a kidney disorder Sleep disorder diagnosis of sleep apnea, restless legs syndrome, periodic limb movement disorder, or narcolepsy Any unstable medical condition Working a night/rotating shift Abnormal screening blood tests Current participation in another drug trial or intervention study Inability or unwillingness to complete the study procedures

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open-label gabapentin<br>Dose titration of 100mg for 1 week, 300mg for 3 weeks, and 600mg for 3 weeks. | Drug: Gabapentin<br>* 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.<br>* Other names: Neurontin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability of Gabapentin | 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. | Baseline, Week 4 visit, and study completion at 7 weeks | 
| Reason for Non-tolerability and Discontinuation of Gabapentin | Reason why subjects who initiated treatment with gabapentin chose to discontinue before study completion | Baseline, Week 4 Visit, and study completion at 7 weeks | 
| Vasomotor Symptoms (VMS) Frequency, Severity, and Bothersomeness During Daytime | 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. | Baseline, study completion at 7 weeks | 
| Vasomotor Symptoms (VMS) Frequency, Severity, and Bothersomeness During Nighttime | 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. | Baseline, study completion at 7 weeks | 
| Severity of Insomnia | 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. | Baseline, study completion at 7 weeks | 
| Sleep Quality and Disturbances Over Past Month | 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. | Baseline, study completion at 7 weeks |