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

Menopause Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02040532
• Other study ID #: 2013P002196
• Secondary ID: 5U01AG032700-05
• Status: Completed
• Phase: N/A
• Start date: January 2014
• Est. completion date: August 2015

Study information

• Verified date: July 2019
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 40 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Hot Flashes
• Menopause
• Vasomotor Disturbance

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Brigham and Women's Hospital, National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

References & Publications (8)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Quality of Life-Overall	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.	Baseline, study completion at 7 weeks
Other	Quality of Life-Menopause Specific	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.	Baseline, study completion at 7 weeks
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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