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Trial record 2 of 54 for:    neurology AND University AND San Francisco | Recruiting, Not yet recruiting, Available Studies

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

This study is currently recruiting participants.
See Contacts and Locations
Verified May 2017 by Riley Bove, MD, University of California, San Francisco
Sponsor:
Collaborator:
National Multiple Sclerosis Society
Information provided by (Responsible Party):
Riley Bove, MD, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT02710214
First received: March 11, 2016
Last updated: May 4, 2017
Last verified: May 2017
  Purpose
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 Intervention Phase
Menopause Multiple Sclerosis Drug: Tissue Selective Estrogen Complex Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by Riley Bove, MD, University of California, San Francisco:

Primary Outcome Measures:
  • 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.


Estimated Enrollment: 24
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)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 62 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02710214

Contacts
Contact: Riley M Bove, MD riley.bove@ucsf.edu
Contact: Ari Green agreen@ucsf.edu

Locations
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
Investigators
Principal Investigator: Riley M Bove, MD Assistant Professor of Clinical Neurology
  More Information

Publications:

Responsible Party: Riley Bove, MD, Assistant Professor of Clinical Neurology, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02710214     History of Changes
Other Study ID Numbers: P0512236
Study First Received: March 11, 2016
Last Updated: May 4, 2017

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

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

ClinicalTrials.gov processed this record on June 27, 2017