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

Primary Purpose

Menopause, Hot Flashes, Vasomotor Disturbance

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Gabapentin
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Menopause

Eligibility Criteria

40 Years - 65 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Females aged 40-65 years
  2. Postmenopausal or perimenopausal
  3. Having bothersome hot flashes
  4. Having some bothersome hot flashes during the night
  5. Insomnia or problems sleeping
  6. In general, good health
  7. Signed informed consent

Exclusion Criteria:

  1. Recent use of hormone therapy or hormonal contraceptives (with the exception of the Mirena IUD)
  2. Recent use of any prescribed therapy that is taken specifically for hot flashes
  3. Recent use of any over-the-counter or herbal therapies that are taken specifically for hot flashes
  4. Recent use of any prescribed medications with known hot flash efficacy
  5. Known hypersensitivity or contraindications (reasons not to take) to gabapentin
  6. Not using a medically approved method of birth control, if sexually active and not 12 or more months since last menstrual period
  7. Recent drug or alcohol abuse
  8. Lifetime diagnosis of psychosis or bipolar disorder
  9. Suicide attempt in the past 3 years or any current suicidal ideation
  10. Current major depression (assessed during screening)
  11. Pregnancy, intending pregnancy, or breast feeding

  12. History of:

    1. Renal insufficiency or a kidney disorder
    2. Sleep disorder diagnosis of sleep apnea, restless legs syndrome, periodic limb movement disorder, or narcolepsy
  13. Any unstable medical condition
  14. Working a night/rotating shift
  15. Abnormal screening blood tests
  16. Current participation in another drug trial or intervention study
  17. Inability or unwillingness to complete the study procedures

Sites / Locations

  • Massachusetts General Hospital
  • Brigham and Women's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Open-label gabapentin

Arm Description

Dose titration of 100mg for 1 week, 300mg for 3 weeks, and 600mg for 3 weeks.

Outcomes

Primary Outcome Measures

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.
Reason for Non-tolerability and Discontinuation of Gabapentin
Reason why subjects who initiated treatment with gabapentin chose to discontinue before study completion
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.
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.
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.
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.

Secondary Outcome Measures

Full Information

First Posted
January 16, 2014
Last Updated
July 29, 2019
Sponsor
Massachusetts General Hospital
Collaborators
Brigham and Women's Hospital, National Institute on Aging (NIA)
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1. Study Identification

Unique Protocol Identification Number
NCT02040532
Brief Title
Gabapentin for Insomnia Symptoms and Nighttime Vasomotor Symptoms (VMS) in Peri- and Postmenopausal Women
Official Title
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.
Study Type
Interventional

2. Study Status

Record Verification Date
July 2019
Overall Recruitment Status
Completed
Study Start Date
January 2014 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
August 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Brigham and Women's Hospital, National Institute on Aging (NIA)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Menopause, Hot Flashes, Vasomotor Disturbance

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Open-label gabapentin
Arm Type
Experimental
Arm Description
Dose titration of 100mg for 1 week, 300mg for 3 weeks, and 600mg for 3 weeks.
Intervention Type
Drug
Intervention Name(s)
Gabapentin
Other Intervention Name(s)
Neurontin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Tolerability of Gabapentin
Description
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.
Time Frame
Baseline, Week 4 visit, and study completion at 7 weeks
Title
Reason for Non-tolerability and Discontinuation of Gabapentin
Description
Reason why subjects who initiated treatment with gabapentin chose to discontinue before study completion
Time Frame
Baseline, Week 4 Visit, and study completion at 7 weeks
Title
Vasomotor Symptoms (VMS) Frequency, Severity, and Bothersomeness During Daytime
Description
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.
Time Frame
Baseline, study completion at 7 weeks
Title
Vasomotor Symptoms (VMS) Frequency, Severity, and Bothersomeness During Nighttime
Description
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.
Time Frame
Baseline, study completion at 7 weeks
Title
Severity of Insomnia
Description
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.
Time Frame
Baseline, study completion at 7 weeks
Title
Sleep Quality and Disturbances Over Past Month
Description
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.
Time Frame
Baseline, study completion at 7 weeks
Other Pre-specified Outcome Measures:
Title
Quality of Life-Overall
Description
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.
Time Frame
Baseline, study completion at 7 weeks
Title
Quality of Life-Menopause Specific
Description
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.
Time Frame
Baseline, study completion at 7 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lee S Cohen, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02116
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
22433978
Citation
Ensrud KE, Joffe H, Guthrie KA, Larson JC, Reed SD, Newton KM, Sternfeld B, Lacroix AZ, Landis CA, Woods NF, Freeman EW. Effect of escitalopram on insomnia symptoms and subjective sleep quality in healthy perimenopausal and postmenopausal women with hot flashes: a randomized controlled trial. Menopause. 2012 Aug;19(8):848-55. doi: 10.1097/gme.0b013e3182476099.
Results Reference
background
PubMed Identifier
20035910
Citation
Joffe H, Petrillo L, Viguera A, Koukopoulos A, Silver-Heilman K, Farrell A, Yu G, Silver M, Cohen LS. Eszopiclone improves insomnia and depressive and anxious symptoms in perimenopausal and postmenopausal women with hot flashes: a randomized, double-blinded, placebo-controlled crossover trial. Am J Obstet Gynecol. 2010 Feb;202(2):171.e1-171.e11. doi: 10.1016/j.ajog.2009.10.868. Epub 2009 Dec 24.
Results Reference
background
PubMed Identifier
17138773
Citation
Soares CN, Joffe H, Rubens R, Caron J, Roth T, Cohen L. Eszopiclone in patients with insomnia during perimenopause and early postmenopause: a randomized controlled trial. Obstet Gynecol. 2006 Dec;108(6):1402-10. doi: 10.1097/01.AOG.0000245449.97365.97.
Results Reference
background
PubMed Identifier
19708803
Citation
Yurcheshen ME, Guttuso T Jr, McDermott M, Holloway RG, Perlis M. Effects of gabapentin on sleep in menopausal women with hot flashes as measured by a Pittsburgh Sleep Quality Index factor scoring model. J Womens Health (Larchmt). 2009 Sep;18(9):1355-60. doi: 10.1089/jwh.2008.1257.
Results Reference
background
PubMed Identifier
17917611
Citation
Butt DA, Lock M, Lewis JE, Ross S, Moineddin R. Gabapentin for the treatment of menopausal hot flashes: a randomized controlled trial. Menopause. 2008 Mar-Apr;15(2):310-8. doi: 10.1097/gme.0b013e3180dca175.
Results Reference
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PubMed Identifier
16139656
Citation
Pandya KJ, Morrow GR, Roscoe JA, Zhao H, Hickok JT, Pajon E, Sweeney TJ, Banerjee TK, Flynn PJ. Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial. Lancet. 2005 Sep 3-9;366(9488):818-24. doi: 10.1016/S0140-6736(05)67215-7.
Results Reference
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PubMed Identifier
16816054
Citation
Reddy SY, Warner H, Guttuso T Jr, Messing S, DiGrazio W, Thornburg L, Guzick DS. Gabapentin, estrogen, and placebo for treating hot flushes: a randomized controlled trial. Obstet Gynecol. 2006 Jul;108(1):41-8. doi: 10.1097/01.AOG.0000222383.43913.ed.
Results Reference
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PubMed Identifier
20050764
Citation
Aguirre W, Chedraui P, Mendoza J, Ruilova I. Gabapentin vs. low-dose transdermal estradiol for treating post-menopausal women with moderate to very severe hot flushes. Gynecol Endocrinol. 2010 May;26(5):333-7. doi: 10.3109/09513590903511539.
Results Reference
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Gabapentin for Insomnia Symptoms and Nighttime Vasomotor Symptoms (VMS) in Peri- and Postmenopausal Women

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