A TSEC for Symptom Management in Menopausal Women With Multiple Sclerosis (MS-TSEC)
Drug: Tissue Selective Estrogen Complex
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Effect of a Tissue Selective Estrogen Complex on Menopausal Symptoms in Women With MS: A Pilot Trial.|
- Menopausal symptoms improves in MS women [ Time Frame: 8 weeks ]By measuring the number of daily vasomotor symptoms (VMS) and sleep quality recorded in the patient diary, the investigstors will assess the success if the observed mean change in the treatment group is larger than the amount in the placebo group.
- Improvement in MS-related outcomes [ Time Frame: 8 weeks ]The outcomes will include MSQOL54 composite score (primary), measures of mood (CES-D), fatigue (MFIS), cognition (MSNQ), and bladder (MSQLI BLCS), and our primary outcome is the MSRS, a global score capturing patient impressions of MS severity across eight function domains, and in which the clinic population has shown good correlation with the EDSS.
- CE+BZA is tolerable in women with MS [ Time Frame: 8 weeks ]The primary measure will be the percentage of subjects reporting side effects on the Satisfaction Questionnaire for Medication (TSQM)(Atkinson et al., 2004), which is commonly used in MS treatment studies. The secondary measures will be number of missed doses, and the number of new or enhancing lesions on 8-week MRI, to verify that CE+BZA does not yield any marked changes in inflammatory activity.
|Study Start Date:||February 2016|
|Estimated Study Completion Date:||December 2018|
|Estimated Primary Completion Date:||December 2017 (Final data collection date for primary outcome measure)|
1 Tablet of 0.45mg conjugated estrogens/20 mg bazedoxifene daily for 8 weeks
Drug: Tissue Selective Estrogen Complex
Once-daily dosing of Duavee for 8 weeks.
Placebo Comparator: Placebo
Placebo pill daily for 8 weeks.
Once-daily dosing of placebo for 8 weeks
Menopause in MS. Multiple sclerosis (MS) affects 3 times more women than men, and before age 50 in about 90% cases, i.e. prior to menopause. There is broad evidence for hormonal regulation of MS in animal models and in clinical cohorts. Around menopause, many clinical patients report symptom worsening associated with hot flashes, sleep disturbance or mood changes. Additionally, individuals at MS may be at increased risk of developing osteoporosis. Longer-term, an age-related decline in gonadal steroids might represent one sex-specific influence on the known age-related increases in disability and conversion to progressive course, which is marked by accelerated brain volume loss and neurodegeneration. Recent data suggest that MS disease severity may worsen after menopause.
- Hormone therapy (HT). In healthy women, after the abrupt decline in estradiol occurring with early oophorectomy, there is an increased risk for cognitive decline and dementia and gray matter (GM) loss in functionally important regions (e.g. hippocampus). Hormonal therapy (HT), when taken within a perimenopausal "window of opportunity" (5 years), may protect against neurodegeneration. Despite the benefits of HT (menopausal symptoms, bone density), very few women (<30% of our cohort) are currently taking HT for menopausal symptoms; this is a result of risks such as (1) breast and endometrial cancer, and (2) stroke in older women in the Women's Health Initiative. To date, there are no objective assessments of the impact of HT on MS disease course.
- Study Drug. Duavee, a tissue selective estrogen complex (TSEC), combines conjugated estrogens (CE) with the selective estrogen receptor modulator (SERM) bazedoxifene (BZA). BZA offsets estrogenic stimulation of endometrial and breast tissue, and CE 0.45mg/BZA 20mg is approved for menopausal symptom (hot flash) relief and osteoporosis prevention, with a favorable tolerability and safety profile. Additionally, two recent randomized clinical trials of estrogenic compounds in MS [estriol (Voskuhl et al) and of ethinylestradiol 40 μg and desogestrel 125 μg (Pozzili et al 2015) found either a neutral or beneficial effect on inflammatory outcomes. Altogether, these findings suggest that CE+BZA may be a promising and safe agent in MS.
In the current study, 24 women with MS and who are experiencing bothersome menopause symptoms will be enrolled and randomized to receive either 8 weeks of Duavee or 8 weeks of placebo. Visits will be: eligibility, baseline, and 2 month visit.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02710214
|Contact: Riley M Bove, MDfirstname.lastname@example.org|
|Contact: Ari Greenemail@example.com|
|United States, California|
|University of California, San Francisco||Recruiting|
|San Francisco, California, United States, 94158|
|Principal Investigator:||Riley M Bove, MD||Assistant Professor of Clinical Neurology|