Clinical trial NCT02040532: 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
Overall status: COMPLETED
Phase: NA
Conditions: Menopause
Hot Flashes
Vasomotor Disturbance
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
name: National Institute on Aging (NIA)
First posted: 2014-01-20
Enrollment: 32
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Tolerability of Gabapentin
timeFrame: Baseline, Week 4 visit, and study completion at 7 weeks
measure: Reason for Non-tolerability and Discontinuation of Gabapentin
timeFrame: Baseline, Week 4 Visit, and study completion at 7 weeks
measure: Vasomotor Symptoms (VMS) Frequency, Severity, and Bothersomeness During Daytime
timeFrame: Baseline, study completion at 7 weeks
measure: Vasomotor Symptoms (VMS) Frequency, Severity, and Bothersomeness During Nighttime
timeFrame: Baseline, study completion at 7 weeks
measure: Severity of Insomnia
timeFrame: Baseline, study completion at 7 weeks
measure: Sleep Quality and Disturbances Over Past Month
timeFrame: Baseline, study completion at 7 weeks
Secondary outcomes:
Other outcomes:
measure: Quality of Life-Overall
timeFrame: Baseline, study completion at 7 weeks
measure: Quality of Life-Menopause Specific
timeFrame: Baseline, study completion at 7 weeks
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Lee S Cohen, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.
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.