A TSEC for Symptom Management in Menopausal Women With Multiple Sclerosis
Condition: Menopause; Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Intervention: Tissue Selective Estrogen Complex; Placebo
Intervention description: Once-daily dosing of Duavee for 8 weeks.; Once-daily dosing of placebo for 8 weeks
Intervention MeSH terms: Estrogens
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 24.0
Sex: Female
Minimum age: 18 Years
Maximum age: 62 Years
Healthy volunteers: No
Keywords: Hot flash; Estrogen; Women

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Women aged 40-62 years.

          -  Perimenopausal: 6 months of amenorrhea; women who had a bi-lateral oophorectomy; women
             without a uterus and who still have one or both ovaries, with FSH level > 20 mIU/mL
             and estradiol ≤ 50 pg/mL; women with a uterus who have skipped 2 or more menstrual
             cycles with an amenorrhea interval; women who are using the Mirena IUD or who have had
             an endometrial ablation and who still have one or both ovaries, with FSH level > 20
             mIU/mL and estradiol ≤ 50 pg/mL

          -  Bothersome MS symptoms: Mean of two or more hot flashes/night sweats per 24 hrs; Hot
             flashes/night sweats rated as bothersome ('moderately' to 'a lot') and/or severe
             ('moderate' to 'severe') on 4 or more 12 hour (day/night) blocks of times

          -  In general good health (determined by medical history, blood pressure, and heart rate)

          -  No history of endometrial, ovarian, or breast cancer; No abnormal mammogram in the
             last 2 years; Absence of any current severe or unstable medical illness

        MS considerations:

          -  If using psychotropic medications: no change in the past 3 months

          -  If on DMT, no change in past 6 months Normal vitamin D levels (20-50 ng/mL)

        Exclusion Criteria:

          -  BMI >35 kg/m2 as higher BMI may affect PK/PD

          -  Use of hormone therapy or hormonal contraceptives 2 months prior to enrollment

          -  Use of any prescribed therapy that is taken specifically for hot flashes in the past 1
             month.

          -  Use of any over-the-counter or herbal therapies that are taken specifically for hot
             flashes in the past 2 weeks.

          -  Use of selective estrogen receptor modulators (SERMs) or aromatase inhibitors during
             the 2 months before enrollment.

          -  Known hypersensitivity or contraindications to estrogen.

          -  Drug or alcohol abuse in the past 1 year

          -  Depression: moderate or severe (HAD score > 8) Other psychiatric disease meeting
             DSM-IV criteria

          -  Lifetime diagnosis of psychosis or bipolar disorder.

          -  Pregnancy, intending pregnancy, or breast feeding

        History of any of the following, as determined by clinician review of the potential
        participant's medical history:

          -  Pre-breast cancer or high-risk breast cancer condition;

          -  Abnormal bleeding suggestive of endometrial pre-cancer;

          -  Endometrial hyperplasia;

          -  Asthma, diabetes mellitus, epilepsy, and migraine disorders that are not stable or
             under medical management;

          -  Active or past history of venous or arterial thromboembolism

          -  History of gallstones IF gallbladder intact

          -  Known or suspected estrogen-dependent neoplasia

          -  History of coronary artery disease

          -  Hypersensitivity (angioedema, anaphylaxis) to estrogens, bazedoxifene, or any
             ingredients

          -  Known hepatic impairment or disease

          -  Thyroid dysfunction on thyroid medications

          -  Known hypoparathyroidism

          -  Blood test results indicating:

          -  Liver function tests: AST >2.5 times upper limit of normal; ALT >2.5 times upper limit
             of normal; total bilirubin 1.5 times upper limit of normal;

          -  Kidney test: creatinine >1.5 mg/dL;

          -  Blood count: hematocrit <30%;

          -  Hemoglobin <8 g/dL.

          -  Current participation in another drug trial or intervention study.

          -  Inability or unwillingness to complete the study procedures.

        MS considerations:

          -  Clinical relapse within the last three months (to ensure disease stability)

          -  Steroid treatment in prior 1 month

          -  Evidence of other structural brain disease (e.g. prior stroke)

        MRI considerations:

          -  Metal implants

          -  Prior head trauma

          -  Claustrophobia requiring anxiolytic or sedation, or other contraindication to MRI.