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

NCT02040532 | Completed Results

• 2 other identifiers: 2013P0021965U01AG032700-05
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

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.

Conditions

Menopause; Hot Flashes; Vasomotor Disturbance

Outcome Measures

Primary Outcomes (6)

• 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

Other Outcomes (2)

• Quality of Life-Overall

  Baseline, study completion at 7 weeks

• Quality of Life-Menopause Specific

  Baseline, study completion at 7 weeks

Study Arms (1)

Open-label gabapentin

EXPERIMENTAL

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

Drug: Gabapentin

Interventions

Gabapentin DRUG

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.

Also known as: Neurontin

Open-label gabapentin

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Brigham and Women's Hospital: collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02116, United States

Location

Related Publications (8)

• 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.

  PMID: 22433978 BACKGROUND

• 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.

  PMID: 20035910 BACKGROUND

• 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.

  PMID: 17138773 BACKGROUND

• 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.

  PMID: 19708803 BACKGROUND

• 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.

  PMID: 17917611 BACKGROUND

• 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.

  PMID: 16139656 BACKGROUND

• 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.

  PMID: 16816054 BACKGROUND

• 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.

  PMID: 20050764 BACKGROUND

MeSH Terms

Conditions

Hot Flashes

Interventions

Gabapentin

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amines; Organic Chemicals; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

* lack of control group (important given that previous VMS medication trials have indicated modest placebo response rates) * small sample size * relatively low rate of completion (6 of 26 subjects who received medication did not reach study endpoint)

Results Point of Contact

• Title: Dr. Lee Cohen
• Organization: MGH Center for Women's Mental Health

lcohen2@partners.org

617-724-0816

Study Officials

• Lee S Cohen, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Center for Women's Mental Health

Study Record Dates

• First Submitted: January 16, 2014
• First Posted: January 20, 2014
• Study Start: January 1, 2014
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: August 7, 2019
• Results First Posted: February 27, 2017

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)