MenopausePhase 2MS-TSECNCT02710214

A TSEC for Symptom Management in Menopausal Women With Multiple Sclerosis

A Phase 2 study testing Tissue Selective Estrogen Complex in people with Menopause and Multiple Sclerosis, run by University of California, San Francisco at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 62 years, women only
Conditions the study is for: Menopause, Multiple Sclerosis
What is being tested?: Tissue Selective Estrogen Complex
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 24 participants
Where: 1 siteUnited States
Study dates: Feb 2016to 24 Apr 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 62 years
Women only
No healthy volunteers
Adult

Who may be able to join

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)

Who cannot join

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.

Show all 38Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of California, San Francisco
San Francisco, California, 94158

Other trials in United States

About this study

Official title: Effect of a Tissue Selective Estrogen Complex on Menopausal Symptoms in Women With MS: A Pilot Trial.

Read the 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.

Conditions: Menopause, Multiple Sclerosis
Being tested: Tissue Selective Estrogen Complex, Placebo
Keywords: Hot flash, Estrogen, Women
Medical subject headings: Multiple Sclerosis, Hot Flashes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Tissue Selective Estrogen ComplexDrug
Also called Duavee, TSEC
Once-daily dosing of Duavee for 8 weeks.
PlaceboDrug
Once-daily dosing of placebo for 8 weeks

Study groups in NCT02710214
Study group	Role	What they receive
Duavee	Experimental	1 Tablet of 0.45mg conjugated estrogens/20 mg bazedoxifene daily for 8 weeks Receives: Drug: Tissue Selective Estrogen Complex
Placebo	Placebo comparator	Placebo pill daily for 8 weeks. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline and 8 weeks

Secondary outcomes (9)

Change in the MS Quality of Life 54 (MSQOL-54)
MS Quality of Life 54 (MSQOL-54) composite scores provide a patient reported quality of life score assessing physical QOL and mental QOL. A sub-scale of this assessment also assesses energy QOL. These will be measured at baseline and end of study (8 weeks). These scores fall within the range of 0 to 100; higher scores indicate better QOL within that domain or sub-scale.
Measured: Baseline and 8 weeks
Change in the Bladder Control Scale (BLCS)
Bladder function will be assessed using the BLCS. Patient reported scores will be collected at baseline and at the end of study (8 weeks); scores fall within the range of 0 to 12. Higher scores indicate worse bladder function.
Measured: Baseline and 8 weeks
Change in the Multiple Sclerosis Rating Scale (MSRS)
Patient reported disability will be measured by the MSRS at baseline and end of study (8 weeks). Scores range of 0 to 32; higher scores indicate worse patient reported disability.
Measured: Baseline and 8 weeks
Change in the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ)
Cognitive function will be assessed by the MSNQ at baseline and end of study (8 weeks). Scores range 0 to 60 (scores >27 indicate cognitive impairment).
Measured: Baseline and 8 weeks
Change in the Symbol Digit Modalities Test (SDMT) Raw Score
SDMT is a screening instrument commonly used in clinical and research settings to assess cognitive dysfunction in MS. The SDMT will be administered at baseline and end of study (8 weeks). The final raw score is the correct number responses completed in 90 seconds and scores range between 0 and 110; higher scores indicate better performance.
Measured: Baseline and 8 weeks
Change in SDMT Z-score
Regression-based norms for the SDMT were used to convert participants' raw scores at baseline and end of study (8 weeks) to demographically adjusted Z-scores, correcting for the effects of age, gender, and education. Scores are normalized so that 0 represents the mean, scores above 0 fall above the mean and are associated with greater performance on the SDMT. Scores below 0 fall below the mean and are associated with poorer performance on the SDMT.
Measured: Baseline and 8 weeks
Change in Letter Number Sequencing (LNS) Performance
The LNS is administered to asses working memory and processing speed at baseline and end of study (8 weeks). The score range is 0 to 21; higher scores indicate better performance on this test.
Measured: Baseline and 8 weeks
Number of Participants With New or Enhancing Lesions on MRI
To verify that CE+BZA does not yield any marked changes in inflammatory activity, a randomized subset of 12 participants will undergo MRI at baseline and end of study (8 weeks) to evaluate for new T2 lesions and new gadolinium enhancing lesions.
Measured: 8 weeks
Number of Missed Doses
The number of missed doses will be assed at the end of study visit.
Measured: 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 201624 Apr 2019

First posted16 Mar 2016 (estimated)
Study startFeb 2016
Primary completion24 Apr 2019
Study completion24 Apr 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (10)Papers the sponsor has linked to this study.
Other trials for MenopauseStudies of the same condition, open and under way.
More trials run by University of California, San FranciscoThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02710214
Sponsor's protocol ID: P0512236
Acronym: MS-TSEC
Status last verified: Jun 2020
First submitted: 11 Mar 2016
Last updated: 15 Jul 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 26447063
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.
PubMed 24101131
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.
PubMed 25787049
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.
PubMed 19031437
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.
PubMed 16837880
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.
PubMed 24336141
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.
PubMed 22367731
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.
PubMed 26140279
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.
PubMed 26621682
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.
PubMed 37715710

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 15 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effect of a Tissue Selective Estrogen Complex on Menopausal Symptoms in Women With MS: A Pilot Trial.
ClinicalTrials.gov ID: NCT02710214
Acronym / sponsor ID: MS-TSEC / P0512236
Conditions: Menopause, Multiple Sclerosis
Keywords: Hot flash, Estrogen, Women
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: University of California, San FranciscoUniversity, hospital or other
Collaborators: National Multiple Sclerosis Society
Study start: Feb 2016
Primary completion: 24 Apr 2019 (actual)
Study completion: 24 Apr 2019 (actual)
First posted: 16 Mar 2016 (estimated)
Results: Posted 29 Jun 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Duavee	Experimental	Drug: Tissue Selective Estrogen Complex1 Tablet of 0.45mg conjugated estrogens/20 mg bazedoxifene daily for 8 weeks
Placebo	Placebo comparator	Drug: PlaceboPlacebo pill daily for 8 weeks.

Who may qualify

Ages: 18 to 62 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (8 listed)

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

Key exclusion criteria (38 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Tissue Selective Estrogen ComplexAlso: Duavee, TSECOnce-daily dosing of Duavee for 8 weeks.	Drug	Duavee
PlaceboOnce-daily dosing of placebo for 8 weeks	Drug	Placebo

Primary outcome

Hot Flash Related Daily Interference Scale (HFRDIS) Score
Time frame: Baseline and 8 weeks
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.
Change in Number of Participants Who Experienced a Reduction in Hot Flashes Per 24 Hours From Baseline to 8 Weeks
Time frame: Baseline and 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.
Change in Average Hot Flashes Per Day From Baseline to 8 Weeks
Time frame: Baseline and 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.
Number of Participants Reporting Side Effects on the Treatment Satisfaction Questionnaire for Medication (TSQM)
Time frame: 8 weeks
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.
Change in the Expanded Disability Status Scale (EDSS)
Time frame: Baseline and 8 weeks
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.

9 secondary outcomes

Change in the MS Quality of Life 54 (MSQOL-54)
Time frame: Baseline and 8 weeks
Change in the Bladder Control Scale (BLCS)
Time frame: Baseline and 8 weeks
Change in the Multiple Sclerosis Rating Scale (MSRS)
Time frame: Baseline and 8 weeks
Change in the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ)
Time frame: Baseline and 8 weeks
Change in the Symbol Digit Modalities Test (SDMT) Raw Score
Time frame: Baseline and 8 weeks
Change in SDMT Z-score
Time frame: Baseline and 8 weeks
Change in Letter Number Sequencing (LNS) Performance
Time frame: Baseline and 8 weeks
Number of Participants With New or Enhancing Lesions on MRI
Time frame: 8 weeks
Number of Missed Doses
Time frame: 8 weeks

Results and safety

Results posted to the registry on 29 Jun 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Duavee	12	11
Placebo	12	10

Primary outcome: Hot Flash Related Daily Interference Scale (HFRDIS) Score

Time frame: Baseline and 8 weeks. Median (Inter-Quartile Range). Unit: score on a scale

Measure	Duavee n = 11	Placebo n = 10
Value	4 (0.5 to 14)	9 (0 to 33)

Population analysed: Data for this measure available only for 21 participants, due to missing data.

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

Time frame: Baseline and 8 weeks. Count of participants. Unit: Participants

Measure	Duavee n = 9	Placebo n = 9
Value	9	8

Population analysed: Data for this measure available only for 18 participants, due to missing data; in 3 cases, weeks 1-2 of on- study data was used when baseline was unavailable.

Primary outcome: Change in Average Hot Flashes Per Day From Baseline to 8 Weeks

Time frame: Baseline and 8 weeks. Median (Inter-Quartile Range). Unit: hot flashes/day

Measure	Duavee n = 10	Placebo n = 11
Value	-2.1 (-3.8 to 0.3)	-2.6 (-7.1 to -0.6)

Population analysed: Data for this measure available only for 21 participants, due to missing data; in 3 cases, weeks 1-2 of on- study data was used when baseline was unavailable.

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

Time frame: 8 weeks. Count of participants. Unit: Participants

Measure	Duavee n = 9	Placebo n = 7
Value	2	1

Population analysed: Data for this measure available only for 16 participants, due to missing data.

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: 8 weeks, from start of study medication (at baseline visit) to end of study visit.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Duavee	0 of 12 (0%)	0 of 12 (0%)	0 of 12
Placebo	0 of 12 (0%)	0 of 12 (0%)	1 of 12

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 26447063Bove 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: PubMed 24101131Bove 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: PubMed 25787049Bove 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: PubMed 19031437Bebo 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: PubMed 16837880Boccardi 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: PubMed 24336141Bove 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: PubMed 22367731North 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: PubMed 26140279Pozzilli 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: PubMed 26621682Voskuhl 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.
Derived from this study: PubMed 37715710Morales-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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Riley M Bove, MD principal investigator

Assistant Professor of Clinical Neurology

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tissue Selective Estrogen Complex in people with Menopause and Multiple Sclerosis, run by University of California, San Francisco at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Hot Flash Related Daily Interference Scale (HFRDIS) Score (time frame: Baseline and 8 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02710214, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2020.