A TSEC for Symptom Management in Menopausal Women With Multiple Sclerosis
Condition: Menopause; Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Interventional
Phase: Phase 2

Summary: 
      Duavee is a hormone receptor modulator that has been approved for the treatment of menopausal
      symptoms in menopausal women. The goal of this 8-week randomized, double blind, placebo
      controlled pilot study, is to determine whether this medication alleviates menopausal
      symptoms in women with MS. The investigators will secondarily determine whether addressing
      menopausal symptoms ameliorates MS symptoms and, on MRIs, is not triggering worsening
      inflammation.
    

Detailed description: 
      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). 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. Recent data on HT use in MS (Nurses Health
           Study) did not show any adverse effects on MS course, and women who used HT reported
           better physical function than women who did not (Bove et al, Neurology 2016).

        -  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.

      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.
    

Intervention name(s): Tissue Selective Estrogen Complex; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Once-daily dosing of Duavee for 8 weeks.; Once-daily dosing of placebo for 8 weeks
Other intervention name(s): Duavee; TSEC
Intervention MeSH terms: Estrogens
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Hot flash; Estrogen; Women