A TSEC for Symptom Management in Menopausal Women With Multiple Sclero
Effect of a Tissue Selective Estrogen Complex on Menopausal Symptoms in Women With MS: A Pilot Trial.
What it found
Results are posted in the registry, but without a statistical test of the main measure. See the numbers below.
What was tested
Treatment tested
- Tissue Selective Estrogen Complex
Placebo
- Placebo
Results by group
Hot Flash Related Daily Interference Scale (HFRDIS) Score
Baseline and 8 weeks
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Duavee | 4 score on a scale | 0.5–14 | 11 |
| Placebo | 9 score on a scale | 0–33 | 10 |
Duavee
Placebo
Change in Number of Participants Who Experienced a Reduction in Hot Flashes Per 24 Hours From Baseline to 8 Weeks
Baseline and 8 weeks
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Duavee | 9 Participants | 9 | |
| Placebo | 8 Participants | 9 |
Duavee
Placebo
Change in Average Hot Flashes Per Day From Baseline to 8 Weeks
Baseline and 8 weeks
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Duavee | -2.1 hot flashes/day | -3.8–0.3 | 10 |
| Placebo | -2.6 hot flashes/day | -7.1–-0.6 | 11 |
Duavee
Placebo
Number of Participants Reporting Side Effects on the Treatment Satisfaction Questionnaire for Medication (TSQM)
8 weeks
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Duavee | 2 Participants | 9 | |
| Placebo | 1 Participants | 7 |
Duavee
Placebo
Change in the Expanded Disability Status Scale (EDSS)
Baseline and 8 weeks
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Duavee | -0.5 units on a scale | -0.5–0 | 11 |
| Placebo | 0 units on a scale | -0.5–0 | 10 |
Duavee
Placebo
Values as posted on ClinicalTrials.gov. Outcomes measured differently across trials are not directly comparable.
Safety
| Group | Participants at risk | Serious adverse events | Deaths |
|---|---|---|---|
| Duavee | 12 | 0 (0.0%) | 0 |
| Placebo | 12 | 0 (0.0%) | 1 |
As posted on ClinicalTrials.gov. Serious adverse events include any serious health event during the trial, whether or not the treatment caused it.
What it measured
Main measures
Hot Flash Related Daily Interference Scale (HFRDIS) Score
Baseline and 8 weeks
Change in Number of Participants Who Experienced a Reduction in Hot Flashes Per 24 Hours From Baseline to 8 Weeks
Baseline and 8 weeks
Change in Average Hot Flashes Per Day From Baseline to 8 Weeks
Baseline and 8 weeks
Number of Participants Reporting Side Effects on the Treatment Satisfaction Questionnaire for Medication (TSQM)
8 weeks
Quality of life (reported by participants)SafetyChange in the Expanded Disability Status Scale (EDSS)
Baseline and 8 weeks
Disability progression
Other measures (9)
Change in the MS Quality of Life 54 (MSQOL-54)
Baseline and 8 weeks
Walking and mobilityQuality of life (reported by participants)Change in the Bladder Control Scale (BLCS)
Baseline and 8 weeks
Walking and mobilityBladder, bowel and sexual functionQuality of life (reported by participants)Change in the Multiple Sclerosis Rating Scale (MSRS)
Baseline and 8 weeks
Quality of life (reported by participants)Change in the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ)
Baseline and 8 weeks
Thinking and memoryChange in the Symbol Digit Modalities Test (SDMT) Raw Score
Baseline and 8 weeks
Thinking and memoryChange in SDMT Z-score
Baseline and 8 weeks
Thinking and memoryWalking and mobilityChange in Letter Number Sequencing (LNS) Performance
Baseline and 8 weeks
Thinking and memoryNumber of Participants With New or Enhancing Lesions on MRI
8 weeks
MRI lesionsNumber of Missed Doses
8 weeks
Who could take part
MS (type not specified) · 18 to 62
Show the full 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.
As registered. Criteria can change, so ask the trial team or your neurologist.
About this trial
In the sponsor's words
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.
Papers
Results
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.Background
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.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.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.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.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.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.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.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.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 randomi
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History
Started
Feb 2016
Main results due
Apr 2019
Finished
Apr 2019
Results posted
Jun 2020