A TSEC for Symptom Management in Menopausal Women With Multiple Sclerosis

NCT02710214 | Completed Phase 2 Results

• 1 other identifier: P0512236
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Menopause; Multiple Sclerosis

Keywords

Hot flash; Estrogen; Women

Outcome Measures

Primary Outcomes (5)

• Hot Flash Related Daily Interference Scale (HFRDIS) Score

  The interference of vasomotor symptoms (VMS) with daily life will be assessed using the HFRDIS. Scores range from 0 to 100; higher scores indicate greater interference of hot flashes with daily life.

  Baseline and 8 weeks

• Change in Number of Participants Who Experienced a Reduction in Hot Flashes Per 24 Hours From Baseline to 8 Weeks

  The number of daily vasomotor symptoms (VMS) will be collected in the form of hot flashes per 24 hours. The average hot flashes per day will be determined at 2 week intervals (baseline, 2 weeks, 4 weeks, and 8 weeks). The number of women experiencing reduction in hot flashes at week 8 compared to baseline will be counted; when baseline data is unavailable 1-2 week on study data will be used.

  Baseline and 8 weeks

• Change in Average Hot Flashes Per Day From Baseline to 8 Weeks

  The number of daily vasomotor symptoms (VMS) will be collected in the form of hot flashes per 24 hours. The average hot flashes per day will be determined at 2 week intervals (baseline, 2 weeks, 4 weeks, and 8 weeks). The average reduction in hot flashes per day over the course of the trial will be determined from the difference between 8 week and baseline frequency (by randomization group, treatment or placebo). When baseline data is not available, the 2 weeks on study data will be used as 'baseline'. Differences \<0 indicate reduction in hot flash frequency over the course of the trial.

  Baseline and 8 weeks

• Number of Participants Reporting Side Effects on the Treatment Satisfaction Questionnaire for Medication (TSQM)

  The primary measure will be the percentage of subjects reporting side effects (yes or no) on the Satisfaction Questionnaire for Medication (TSQM). The TSQM is used to assess patients' satisfaction with medication, providing scores on four scales - side effects, effectiveness, convenience and global satisfaction.

  8 weeks

• Change in the Expanded Disability Status Scale (EDSS)

  EDSS total score is a metric used for quantifying disability in MS and monitoring changes in the level of disability over time. The EDSS will be assessed by a the trial neurologist at baseline and end of study (8 weeks). The score range is 0 to 10; higher scores indicate greater disability. All analyses were performed according to the intention-to-treat principle (primary) then the per-protocol principle.

  Baseline and 8 weeks

Secondary Outcomes (9)

• Change in the MS Quality of Life 54 (MSQOL-54)

  Baseline and 8 weeks

• Change in the Bladder Control Scale (BLCS)

  Baseline and 8 weeks

• Change in the Multiple Sclerosis Rating Scale (MSRS)

  Baseline and 8 weeks

• Change in the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ)

  Baseline and 8 weeks

• Change in the Symbol Digit Modalities Test (SDMT) Raw Score

  Baseline and 8 weeks

Study Arms (2)

Duavee

EXPERIMENTAL

1 Tablet of 0.45mg conjugated estrogens/20 mg bazedoxifene daily for 8 weeks

Drug: Tissue Selective Estrogen Complex

Placebo

PLACEBO COMPARATOR

Placebo pill daily for 8 weeks.

Drug: Placebo

Interventions

Tissue Selective Estrogen Complex DRUG

Once-daily dosing of Duavee for 8 weeks.

Also known as: Duavee, TSEC

Duavee

Placebo DRUG

Once-daily dosing of placebo for 8 weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 62 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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;

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Multiple Sclerosis Society: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94158, United States

Location

Related Publications (10)

• Bove R, Healy BC, Musallam A, Glanz BI, De Jager PL, Chitnis T. Exploration of changes in disability after menopause in a longitudinal multiple sclerosis cohort. Mult Scler. 2016 Jun;22(7):935-43. doi: 10.1177/1352458515606211. Epub 2015 Oct 7.

  PMID: 26447063 BACKGROUND

• Bove R, Chitnis T, Houtchens M. Menopause in multiple sclerosis: therapeutic considerations. J Neurol. 2014 Jul;261(7):1257-68. doi: 10.1007/s00415-013-7131-8. Epub 2013 Oct 8.

  PMID: 24101131 BACKGROUND

• Bove R, Healy BC, Secor E, Vaughan T, Katic B, Chitnis T, Wicks P, De Jager PL. Patients report worse MS symptoms after menopause: findings from an online cohort. Mult Scler Relat Disord. 2015 Jan;4(1):18-24. doi: 10.1016/j.msard.2014.11.009. Epub 2014 Dec 9.

  PMID: 25787049 BACKGROUND

• Bebo BF Jr, Dehghani B, Foster S, Kurniawan A, Lopez FJ, Sherman LS. Treatment with selective estrogen receptor modulators regulates myelin specific T-cells and suppresses experimental autoimmune encephalomyelitis. Glia. 2009 May;57(7):777-90. doi: 10.1002/glia.20805.

  PMID: 19031437 BACKGROUND

• Boccardi M, Ghidoni R, Govoni S, Testa C, Benussi L, Bonetti M, Binetti G, Frisoni GB. Effects of hormone therapy on brain morphology of healthy postmenopausal women: a Voxel-based morphometry study. Menopause. 2006 Jul-Aug;13(4):584-91. doi: 10.1097/01.gme.0000196811.88505.10.

  PMID: 16837880 BACKGROUND

• Bove R, Secor E, Chibnik LB, Barnes LL, Schneider JA, Bennett DA, De Jager PL. Age at surgical menopause influences cognitive decline and Alzheimer pathology in older women. Neurology. 2014 Jan 21;82(3):222-9. doi: 10.1212/WNL.0000000000000033. Epub 2013 Dec 11.

  PMID: 24336141 BACKGROUND

• North American Menopause Society. The 2012 hormone therapy position statement of: The North American Menopause Society. Menopause. 2012 Mar;19(3):257-71. doi: 10.1097/gme.0b013e31824b970a.

  PMID: 22367731 BACKGROUND

• Pozzilli C, De Giglio L, Barletta VT, Marinelli F, Angelis FD, Gallo V, Pagano VA, Marini S, Piattella MC, Tomassini V, Pantano P. Oral contraceptives combined with interferon beta in multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2015 Jun 18;2(4):e120. doi: 10.1212/NXI.0000000000000120. eCollection 2015 Aug.

  PMID: 26140279 BACKGROUND

• Voskuhl RR, Wang H, Wu TC, Sicotte NL, Nakamura K, Kurth F, Itoh N, Bardens J, Bernard JT, Corboy JR, Cross AH, Dhib-Jalbut S, Ford CC, Frohman EM, Giesser B, Jacobs D, Kasper LH, Lynch S, Parry G, Racke MK, Reder AT, Rose J, Wingerchuk DM, MacKenzie-Graham AJ, Arnold DL, Tseng CH, Elashoff R. Estriol combined with glatiramer acetate for women with relapsing-remitting multiple sclerosis: a randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2016 Jan;15(1):35-46. doi: 10.1016/S1474-4422(15)00322-1. Epub 2015 Nov 29.

  PMID: 26621682 BACKGROUND

• Morales-Rodriguez D, Anderson A, Nylander A, Hsu S, Singh J, Rowles W, Walsh CM, Braley TJ, Bove R. Well-being at midlife: Correlates of mental health in ambulatory menopausal women with multiple sclerosis. Mult Scler. 2023 Oct;29(11-12):1493-1502. doi: 10.1177/13524585231197056. Epub 2023 Sep 16.

  PMID: 37715710 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis; Hot Flashes

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Planned low sample size and our pre-specified power calculation allowed 80% power to observe a greater mean change in the treatment than in the control arm but did not provide sufficient power to assess statistical significance in this pilot study.

Results Point of Contact

• Title: Dr. Riley Bove
• Organization: University of California, San Francisco

riley.bove@ucsf.edu

415-595-2795

Study Officials

• Riley M Bove, MD

  Assistant Professor of Clinical Neurology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2016
• First Posted: March 16, 2016
• Study Start: February 1, 2016
• Primary Completion: April 24, 2019
• Study Completion: April 24, 2019
• Last Updated: July 15, 2020
• Results First Posted: June 29, 2020

Record last verified: 2020-06

Locations

US (1)