A TSEC for Symptom Management in Menopausal Women With Multiple Sclerosis (MS-TSEC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02710214
Recruitment Status : Recruiting
First Posted : March 16, 2016
Last Update Posted : May 2, 2018
National Multiple Sclerosis Society
Information provided by (Responsible Party):
Riley Bove, MD, University of California, San Francisco

Brief 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.

Condition or disease Intervention/treatment Phase
Menopause Multiple Sclerosis Drug: Tissue Selective Estrogen Complex Drug: Placebo Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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.
Study Start Date : February 2016
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : February 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Estrogens

Arm Intervention/treatment
Experimental: Duavee
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.
Other Names:
  • Duavee
  • TSEC

Placebo Comparator: Placebo
Placebo pill daily for 8 weeks.
Drug: Placebo
Once-daily dosing of placebo for 8 weeks

Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

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Ages Eligible for Study:   18 Years to 62 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02710214

Contact: Riley M Bove, MD
Contact: Ari Green

United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94158
Sponsors and Collaborators
University of California, San Francisco
National Multiple Sclerosis Society
Principal Investigator: Riley M Bove, MD Assistant Professor of Clinical Neurology


Responsible Party: Riley Bove, MD, Assistant Professor of Clinical Neurology, University of California, San Francisco Identifier: NCT02710214     History of Changes
Other Study ID Numbers: P0512236
First Posted: March 16, 2016    Key Record Dates
Last Update Posted: May 2, 2018
Last Verified: May 2018

Keywords provided by Riley Bove, MD, University of California, San Francisco:
Hot flash

Additional relevant MeSH terms:
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs