• P100 Latency on Full Field Visual Evoked Potential [ Time Frame: 3 months ]
  The primary objective is to evaluate the efficacy of BZA relative to placebo for reducing P100 latencies on full field transient pattern reversal visual evoked potentials (VEPs). In response to a visual stimulus, cortically generated electrical potentials (VEPs) recorded over the scalp are used to measure the functional integrity of visual pathways.
• P100 Latency on Full Field Visual Evoked Potential [ Time Frame: 6 months ]
  Assess whether P100 latency delay at 6 months decreases to a greater extent in Group A (exposed to BZA for 3 months during both Stage 1 and Stage 2 -- 6 months total) when compared to Group B (exposed to placebo during Stage 1 and BZA for 3 months during Stage 2 -- 3 months total).

The primary goal of this study is to assess the efficacy of bazedoxifene (BZA) as remyelinating agent in patients with relapsing-remitting multiple sclerosis (RRMS).

The investigators will utilize electrophysiologic techniques and magnetic resonance imaging to quantify the effect of treatment in 50 women over the course of 6 months.

Participants may remain on their standard disease modifying treatment during the course of the trial but may not concurrently participate in any other investigational new drug research study.

Multiple Sclerosis (MS) is a chronic neurologic disorder characterized by the loss of myelin, which results in disruption of nerve signal, damage to axons, and, ultimately, neurodegeneration. In order to treat MS, new methods for promoting repair (remyelination) are sorely needed.

There is a strong preclinical (including EAE) and epidemiologic rationale for investigating the remyelinating potential of estrogenic compounds, including evidence of endogenous (puberty, postpartum periods) and exogenous hormonal influences on MS risk and course. MS affects 3 times more women than men, and disease course in women appears overall less aggressive (on MRI, fewer T2-hyperintense demyelinated lesions develop into axonal destruction visualized as hypointense T1 "black holes").

Bazedoxifene (BZA), a third-generation SERM with extensive safety data in humans, was identified in a novel high-throughput screen (BIMA screen) for compounds capable of promoting remyelination. Subsequent analysis validated BZA's remyelinating effect in vitro and in vivo following demyelinating insult. Given strong pre-clinical support for BZA's remyelinating potential, and the clinical success of other compounds identified using the BIMA screen (Green et al., 2017), the investigators will investigate the use of BZA as a remyelinating therapy in patients with MS.

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting

• Experimental: Group A
  Group A is the "early-start" group and will receive a total of 6 months of BZA -- 3 months of BZA, followed by 3 months BZA
  Intervention: Drug: Bazedoxifene Acetate
• Experimental: Group B
  Group B is the "delayed-start" group and will receive a total of 3 months of BZA -- 3 months of placebo, followed by 3 months of BZA
  Intervention: Drug: Bazedoxifene Acetate

Inclusion Criteria:

1. Women aged 45-65 or 40+ post-menopausal.
2. Documentation of a clinically definite diagnosis of relapsing-remitting MS
3. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.
4. Latency delay > 118 milliseconds on baseline full-field transient pattern reversal VEP in at least one eye (electrophysiological evidence of demyelination)
5. RNFL > 70 microns on SD-OCT in the same eye meeting criteria for latency delay (sufficient axons)
6. Stable immunomodulatory therapy - no switch or planned switch in > 6 months and no change in doses in 30 days prior to screening
7. Use of contraceptive method with ≤1% failure rate during period of trial if premenopausal
8. Understand and sign informed consent.
9. EDSS 0-6.0 (inclusive)

Exclusion Criteria:

1. Multiple Sclerosis disease duration > 25 years
2. Optic neuritis in prior 6 months
3. Known optic neuritis in involved eye ≥ 10 years ago
4. Major ophthalmologic disease/Concomitant ophthalmologic disorders (e.g. diabetes, macular degeneration, glaucoma, severe myopia, etc.).
5. Myopia > -7 Diopters (severe myopia)
6. Disc hemorrhages in qualifying eye
7. No light perception in qualifying eye
8. Simultaneous bilateral optic neuritis
9. Cotton wool spots in qualifying eye
10. Macular star in qualifying eye
11. History of significant cardiac conduction block
12. History of cancer (except non-melanoma skin cancer)
13. Suicidal ideation or behavior in 6 months prior to baseline
14. Pregnancy, breastfeeding, or planning to become pregnant
15. Included with other study protocol simultaneously without prior approval
16. Concomitant or prior use of any other putative remyelinating therapy as determined by investigator, including but not limited to Clemastine, Duavee, and Tamoxifen.
17. Serum creatinine > 1.5mg/dL; AST, ALT, or alkaline phosphatase > 2 times the upper limit of normal
18. History of drug or alcohol abuse within the past year
19. Untreated B12 deficiency (as determined by B12 serological assessments and metabolites including methylmalonic acid [MMA] and homocysteine) or untreated hypothyroidism
20. Clinically significant cardiac, metabolic, hematologic, hepatic, immunologic, urologic, endocrinologic, neurologic, pulmonary, psychiatric, dermatologic, allergic, renal or other major diseases that in the PI's judgement may affect interpretation of study results or patient safety.
21. History of or presence of clinically significant medical illness or laboratory abnormality that, in the opinion of the investigator would preclude participation in the study.
22. Patients whose lack of mobility exposes them to an increased risk of venous thromboembolism
23. Patients with undiagnosed uterine bleeding
24. Patients with unknown, suspected or past history of breast cancer
25. Patients with known or suspected estrogen-dependent neoplasia
26. Patients with active or a past history of venous thromboembolism
27. Patients with active or a past history of arterial thromboembolism
28. Patients with known protein C, protein S, or antithrombin deficiency or other known thrombophilic disorders
29. Patients with hypersensitivity (angioedema, anaphylaxis) to estrogens, bazedoxifene, or any ingredients
30. Patients with known hepatic impairment or disease