Relapsing-remitting Multiple SclerosisPhase 2NCT01466114
Estriol Treatment in Multiple Sclerosis (MS): Effect on Cognition
A Phase 2 study testing estriol and Norethindrone in people with Relapsing-remitting Multiple Sclerosis and Secondary-progressive Multiple Sclerosis, run by University of California, Los Angeles at 4 sites in United States.
Trial summary
Approximately 50% of people diagnosed with Multiple Sclerosis (MS) will develop problems with cognition. Currently, there are no FDA-approved treatments targeting cognitive function in Multiple Sclerosis. Read more about this study
- Who is it for?
- Ages 18 to 55 years, women only
- Conditions the study is for
- Relapsing-remitting Multiple Sclerosis, Secondary-progressive Multiple Sclerosis, Primary-progressive Multiple Sclerosis
- What is being tested?
- estriol and Norethindrone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 4 sitesUnited States
- Study dates
- Oct 2011to Apr 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 55 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Diagnosis of clinically definite or MacDonald criteria relapsing-remitting multiple sclerosis, secondary-progressive multiple sclerosis or primary-progressive multiple sclerosis.
- No relapse within 30 days before day of trial enrollment (month 0 visit). If steroids given for relapse, then the month 0 visit must be 30 days after last steroid dose.
- Females age 18 to 55, inclusive.
- Expanded Disability Status Score (EDSS) = 0.0 to 6.0.
- Screening PASAT (3-second) score 25-50, inclusive.
- Must be mentally competent enough to comply with study guidelines and give informed consent.
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- Must be willing and able to travel to the study center at frequencies in the protocol for a total period of 12 months.
- Patients must be on no treatment or be on a stable dose of one of the following agents for a minimum of 3 months duration prior to the month 0 visit: Copaxone®, Betaseron® (or Extavia®), Rebif®, Avonex®, PLEGRITY®, Ocrelizumab, Rituximab, Gilenya®, Aubagio®, or Tecfidera®. The time spent in the screening period may serve as part of this 3-month period.
- Patients who are currently being treated with ACTH, corticosteroids, intravenous immunoglobulins (IVIG), plasma exchange, Lipitor® or minocycline may be included.
- If patients plan to start treatment with Copaxone® or an interferon [Betaseron® (or Extavia®), Rebif®, Avonex®, PLEGRITY®], Ocrelizumab, Rituximabor an oral agent [Gilenya®, Aubagio® or Tecfidera®] and then they must be on for at least 3 months prior to month 0 (as above).
Who cannot join
- Males
- Subjects on oral contraceptives (OCP), hormone replacement therapy (HRT) other sex hormones during screening and during the 12-month study period (Mirena® IUD is permitted).
- Females who are pregnant or who plan to become pregnant during the 12 months of enrollment, who wish to become pregnant within 3 months following completion of the study, or who will be within 6 months post partum at the day of first enrollment visit (month 0).
- Females who plan to breastfeed after first enrollment visit (month 0).
- Fertile sexually active women who are unwilling to practice reliable barrier methods of contraception other than oral contraceptives (i.e. condom, diaphragm, IUDs Note: Hormonal IUD [Mirena®] is permitted).
- Patients with surgical ovariectomy with no hormone replacement for 1 year or more.
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- Menopause with no hormone replacement for 3 years or more prior to the first enrollment visit.
- Patients who smoke at any time during screening or during the 12 month study period.
- Patients who have serious pulmonary, renal, gastrointestinal, hepatic, immunologic, infectious, neoplastic, major psychiatric disease (major depression, schizophrenia), endocrine disease (including major diabetes, thyroid disease), or gynecologic disease, including but not limited to those with: Thrombophlebitis or thromboembolic disorders, a past history of deep vein thrombophlebitis or thromboembolic disorders, cerebral vascular or coronary artery disease, migraine with focal aura, known or suspected carcinoma of the breast, carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia, undiagnosed abnormal genital bleeding, polycystic ovary disease, amenorrhea of unknown etiology, cholestatic jaundice of pregnancy or jaundice with prior birth control pill use, acute or chronic hepatocellular disease with abnormal liver function, hepatic adenomas or carcinomas, known or suspected pregnancy, known hypersensitivity to birth control pill Copaxone or Betaseron use.
- B12 level < 200.
- Drug abuse within the past five years.
- Conditions that would interfere with assessing neurologic functions such as deforming arthritis or a major amputation.
- Have at any time been treated with total lymphoid irradiation, monoclonal antibody, T cell vaccination, cladribine, bone marrow transplantation, azathioprine, cyclophosphamide, methotrexate, mitoxantrone, or cyclosporine.
- Have been treated with natalizumab (Tysabri®) in the 6 months prior to screening.
- Positive titers to HIV in the past.
- Previous serious adverse effects with estrogen treatment.
- Patients who participated in the previous multi-center estriol trial for RRMS ("A Combination Trial of Copaxone plus Estriol in RRMS").
Trial locations and contacts
4 sites in 1 country.
United States4 sites, 1 recruiting
- Completed
The University of New Mexico
Albuquerque, New Mexico, 87131
- Completed
The University of Colorado Denver
Aurora, Colorado, 80045
- Recruiting
University of California Los Angeles
Los Angeles, California, 90095
Mike Montag, M.S., 310-206-2176, MMontag@mednet.ucla.edu
Barbara Giesser, MD
- Completed
The University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Double-Blind, Placebo Controlled Trial of Estriol Treatment in Women With Multiple Sclerosis: Effect on Cognition.
Approximately 50% of people diagnosed with Multiple Sclerosis (MS) will develop problems with cognition. Currently, there are no FDA-approved treatments targeting cognitive function in Multiple Sclerosis. This trial will ascertain whether treatment with an estrogen pill, used in combination with standard MS anti-inflammatory drugs, can improve cognitive testing as compared to treatment with a placebo pill in combination with standard anti-inflammatory drugs in women with MS.
Read the detailed description
Approximately 50% of people diagnosed with Multiple Sclerosis (MS) will develop problems with cognition. Currently, there are no FDA-approved treatments for cognitive function in Multiple Sclerosis. Multiple sclerosis relapses are known to be significantly decreased by approximately 80% during late pregnancy. This disease improvement may be due to estriol, an estrogen unique to pregnancy. Estriol blood levels go from undetectable levels prior to pregnancy, increase during pregnancy and reach highest levels during late pregnancy. Further, estrogen treatment has been shown to have favorable effects on cognition in animal models of other neurological diseases. This proposal will establish whether oral treatment with estriol, induces an improvement in cognitive functioning in subjects with multiple sclerosis when used in combination with the major FDA-approved standard treatments for MS, (Betaseron® (or Extavia®), Rebif®, Avonex®, Copaxone®, Gilenya®, Aubagio®, Tecfidera®, or Ocrevus®).
The combination of standard MS treatment plus estriol pill (8 mg per day) will be compared to standard MS treatment plus placebo in a double-blinded fashion. The duration of treatment will be one year and the primary outcome measure will be cognitive testing processing speed ability.
Secondary outcomes will be improvement in other cognitive tests, brain MRIs, cognitive evoked potentials, as well as relapse rates and disability measures (EDSS, 25 foot walk, 9 hole peg test, low contrast visual acuity, MS Quality of Life, Modified Fatigue Impact Scale, Beck Depression Inventory, Level of Activity using accelerometry). Safety measures (blood tests and gynecologic evaluations) will also be followed. The overall goal of this study will be the development of an oral treatment, estriol, to improve cognitive function in MS.
- Conditions
- Relapsing-remitting Multiple Sclerosis, Secondary-progressive Multiple Sclerosis, Primary-progressive Multiple Sclerosis
- Being tested
- estriol, Placebo, Norethindrone, Progestin Placebo
- Keywords
- multiple sclerosis, MS, relapsing remitting multiple sclerosis, RRMS, secondary progressive multiple sclerosis, SPMS, primary progressive multiple sclerosis, estrogen, estriol
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Chronic Progressive, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
estriolDrug
Also called Synapause
4 capsules of 2 mg (total of 8 mg) PO QD
PlaceboOther
4 capsules PO QD
NorethindroneDrug
Also called Progestin
Starting at month 6, and at Months 9 and 12: subjects who are on estriol (Group A) take 0.7 mg PO QD for 2 weeks.
Progestin PlaceboOther
Starting at Month 6 and at Months 9 and 12: subjects who are on placebo (Group B) take a second progestin placebo pill PO QD for 2 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Group A: Estriol | Experimental | Standard MS Treatment + Estriol Receives: Drug: estriol; Drug: Norethindrone |
| Group B: Placebo | Placebo comparator | Standard MS Treatment + Placebo Receives: Other: Placebo; Other: Progestin Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in cognitive function assessed by Paced Serial Addition Test (PASAT).
Processing speed will be assessed by PASAT. Numerical test scores (ranging from 0-60) will be acquired, then percent change for each subject at trial conclusion as compared to baseline will be determined. Whether greater improvement as expressed as percent change occurs in the estriol group as compared to the placebo group will be determined.
Measured: 1 year
Secondary outcomes (4)
Change from baseline in cognitive function as assessed by cognitive evoked potentials, measured in milliseconds.
Cognitive evoked potentials will be recorded in msecs for each subject at baseline and conclusion. The percent improvement as conclusion as compared to baseline for each subject will be determined. Group comparisons will reveal whether the percent improvement is greater in the estriol treated group as compared to the placebo treated group.
Measured: 1 year
Change from baseline in standard MS outcome measures.
Determine whether the combination treatment has an effect on standard MS outcome measures (relapses, EDSS, 25 foot walk test, 9 hole peg test, low contrast visual acuity, MS Quality of Life, Modified Fatigue Impact Scare, Beck Depression Inventory.
Measured: 1 year
Determine safety by assessing the number of subjects with adverse events with combination treatment as compared to placebo.
Determine whether the combination treatment is safe (based on neurologic exams, laboratory tests (Chemistries, CBC), and gynecologic exams (breast and gynecologic exams).
Measured: 1 year
Change from baseline in cognitive function as assessed by a brief battery of cognitive tests.
A brief battery of cognitive tests will be administered including: Processing speed: SDMT-hand written; Visual memory: 7/24 Spatial Recall Test, Benton Forms F \& G; Verbal memory: Buschke Selective Reminding Test, Verbal Paired Associates; Language: Word List Generation. Each subject will be tested at baseline, month 6 and conclusion. Percent change at conclusion as compared to baseline will be determined in each subject. Group comparisons will reveal which cognitive test within the battery had greater improvement in the estriol treated group as compared to the placebo treated group.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2011 (estimated)
- Study startOct 2011
- Primary completionDec 2021 (estimated)
- Study completionApr 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Relapsing-remitting Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe 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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rhonda Voskuhl, University of California, Los Angeles
- Investigators
- Rhonda Voskuhl, M.D., Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01466114
- Sponsor's protocol ID
- 11-002055
- Status last verified
- Nov 2019
- First submitted
- 31 Oct 2011
- Last updated
- 6 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Ziehn MO, Avedisian AA, Dervin SM, O'Dell TJ, Voskuhl RR. Estriol preserves synaptic transmission in the hippocampus during autoimmune demyelinating disease. Lab Invest. 2012 Aug;92(8):1234-45. doi: 10.1038/labinvest.2012.76. Epub 2012 Apr 23.
PubMed 22525427Voskuhl 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 26621682Voskuhl R, Wang H, Elashoff RM. Why use sex hormones in relapsing-remitting multiple sclerosis? - Authors' reply. Lancet Neurol. 2016 Jul;15(8):790-791. doi: 10.1016/S1474-4422(16)00129-0. No abstract available.
PubMed 27302354Voskuhl R, Patti F. Hormone replacement in menopausal women with multiple sclerosis: Looking back, thinking forward. Neurology. 2016 Oct 4;87(14):1430-1431. doi: 10.1212/WNL.0000000000003189. Epub 2016 Sep 7. No abstract available.
PubMed 27605172Voskuhl R. Rebound Relapses After Ceasing Another Disease-Modifying Treatment in Patients With Multiple Sclerosis: Are There Lessons to Be Learned? JAMA Neurol. 2016 Jul 1;73(7):775-6. doi: 10.1001/jamaneurol.2016.0934. No abstract available.
PubMed 27136400Itoh N, Kim R, Peng M, DiFilippo E, Johnsonbaugh H, MacKenzie-Graham A, Voskuhl RR. Bedside to bench to bedside research: Estrogen receptor beta ligand as a candidate neuroprotective treatment for multiple sclerosis. J Neuroimmunol. 2017 Mar 15;304:63-71. doi: 10.1016/j.jneuroim.2016.09.017. Epub 2016 Oct 3.
PubMed 27771018Kim RY, Mangu D, Hoffman AS, Kavosh R, Jung E, Itoh N, Voskuhl R. Oestrogen receptor β ligand acts on CD11c+ cells to mediate protection in experimental autoimmune encephalomyelitis. Brain. 2018 Jan 1;141(1):132-147. doi: 10.1093/brain/awx315.
PubMed 29228214MacKenzie-Graham A, Brook J, Kurth F, Itoh Y, Meyer C, Montag MJ, Wang HJ, Elashoff R, Voskuhl RR. Estriol-mediated neuroprotection in multiple sclerosis localized by voxel-based morphometry. Brain Behav. 2018 Sep;8(9):e01086. doi: 10.1002/brb3.1086. Epub 2018 Aug 24.
PubMed 30144306Voskuhl RR, Itoh N, Tassoni A, Matsukawa MA, Ren E, Tse V, Jang E, Suen TT, Itoh Y. Gene expression in oligodendrocytes during remyelination reveals cholesterol homeostasis as a therapeutic target in multiple sclerosis. Proc Natl Acad Sci U S A. 2019 May 14;116(20):10130-10139. doi: 10.1073/pnas.1821306116. Epub 2019 Apr 30.
PubMed 31040210Voskuhl R. It is time to conduct phase 3 clinical trials of sex hormones in MS - Yes. Mult Scler. 2018 Oct;24(11):1413-1415. doi: 10.1177/1352458518768764. Epub 2018 Jul 30. No abstract available.
PubMed 30058469Voskuhl R, Momtazee C. Pregnancy: Effect on Multiple Sclerosis, Treatment Considerations, and Breastfeeding. Neurotherapeutics. 2017 Oct;14(4):974-984. doi: 10.1007/s13311-017-0562-7.
PubMed 28766273
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Placebo Controlled Trial of Estriol Treatment in Women With Multiple Sclerosis: Effect on Cognition.
- ClinicalTrials.gov ID
- NCT01466114
- Acronym / sponsor ID
- 11-002055
- Conditions
- Relapsing-remitting Multiple Sclerosis, Secondary-progressive Multiple Sclerosis, Primary-progressive Multiple Sclerosis
- Keywords
- multiple sclerosis, MS, relapsing remitting multiple sclerosis, RRMS, secondary progressive multiple sclerosis, SPMS, primary progressive multiple sclerosis, estrogen
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 64 participants (estimated)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Study start
- Oct 2011
- Primary completion
- Dec 2021 (estimated)
- Study completion
- Apr 2022 (estimated)
- First posted
- 7 Nov 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Approximately 50% of people diagnosed with Multiple Sclerosis (MS) will develop problems with cognition. Currently, there are no FDA-approved treatments targeting cognitive function in Multiple Sclerosis. This trial will ascertain whether treatment with an estrogen pill, used in combination with standard MS anti-inflammatory drugs, can improve cognitive testing as compared to treatment with a placebo pill in combination with standard anti-inflammatory drugs in women with MS.
Detailed description
Approximately 50% of people diagnosed with Multiple Sclerosis (MS) will develop problems with cognition. Currently, there are no FDA-approved treatments for cognitive function in Multiple Sclerosis. Multiple sclerosis relapses are known to be significantly decreased by approximately 80% during late pregnancy. This disease improvement may be due to estriol, an estrogen unique to pregnancy. Estriol blood levels go from undetectable levels prior to pregnancy, increase during pregnancy and reach highest levels during late pregnancy. Further, estrogen treatment has been shown to have favorable effects on cognition in animal models of other neurological diseases. This proposal will establish whether oral treatment with estriol, induces an improvement in cognitive functioning in subjects with multiple sclerosis when used in combination with the major FDA-approved standard treatments for MS, (Betaseron® (or Extavia®), Rebif®, Avonex®, Copaxone®, Gilenya®, Aubagio®, Tecfidera®, or Ocrevus®).
The combination of standard MS treatment plus estriol pill (8 mg per day) will be compared to standard MS treatment plus placebo in a double-blinded fashion. The duration of treatment will be one year and the primary outcome measure will be cognitive testing processing speed ability.
Secondary outcomes will be improvement in other cognitive tests, brain MRIs, cognitive evoked potentials, as well as relapse rates and disability measures (EDSS, 25 foot walk, 9 hole peg test, low contrast visual acuity, MS Quality of Life, Modified Fatigue Impact Scale, Beck Depression Inventory, Level of Activity using accelerometry). Safety measures (blood tests and gynecologic evaluations) will also be followed. The overall goal of this study will be the development of an oral treatment, estriol, to improve cognitive function in MS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A: Estriol | Experimental | Drug: estriol, Drug: NorethindroneStandard MS Treatment + Estriol |
| Group B: Placebo | Placebo comparator | Other: Placebo, Other: Progestin PlaceboStandard MS Treatment + Placebo |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Diagnosis of clinically definite or MacDonald criteria relapsing-remitting multiple sclerosis, secondary-progressive multiple sclerosis or primary-progressive multiple sclerosis.
- No relapse within 30 days before day of trial enrollment (month 0 visit). If steroids given for relapse, then the month 0 visit must be 30 days after last steroid dose.
- Females age 18 to 55, inclusive.
- Expanded Disability Status Score (EDSS) = 0.0 to 6.0.
- Screening PASAT (3-second) score 25-50, inclusive.
Key exclusion criteria (17 listed)
- Males
- Subjects on oral contraceptives (OCP), hormone replacement therapy (HRT) other sex hormones during screening and during the 12-month study period (Mirena® IUD is permitted).
- Females who are pregnant or who plan to become pregnant during the 12 months of enrollment, who wish to become pregnant within 3 months following completion of the study, or who will be within 6 months post partum at the day of first enrollment visit (month 0).
- Females who plan to breastfeed after first enrollment visit (month 0).
- Fertile sexually active women who are unwilling to practice reliable barrier methods of contraception other than oral contraceptives (i.e. condom, diaphragm, IUDs Note: Hormonal IUD [Mirena®] is permitted).
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 |
|---|---|---|
| estriolAlso: Synapause4 capsules of 2 mg (total of 8 mg) PO QD | Drug | Group A: Estriol |
| Placebo4 capsules PO QD | Other | Group B: Placebo |
| NorethindroneAlso: ProgestinStarting at month 6, and at Months 9 and 12: subjects who are on estriol (Group A) take 0.7 mg PO QD for 2 weeks. | Drug | Group A: Estriol |
| Progestin PlaceboStarting at Month 6 and at Months 9 and 12: subjects who are on placebo (Group B) take a second progestin placebo pill PO QD for 2 weeks. | Other | Group B: Placebo |
Primary outcome
Change from baseline in cognitive function assessed by Paced Serial Addition Test (PASAT).
Time frame: 1 year
Processing speed will be assessed by PASAT. Numerical test scores (ranging from 0-60) will be acquired, then percent change for each subject at trial conclusion as compared to baseline will be determined. Whether greater improvement as expressed as percent change occurs in the estriol group as compared to the placebo group will be determined.
4 secondary outcomes
Change from baseline in cognitive function as assessed by cognitive evoked potentials, measured in milliseconds.
Time frame: 1 year
Change from baseline in standard MS outcome measures.
Time frame: 1 year
Determine safety by assessing the number of subjects with adverse events with combination treatment as compared to placebo.
Time frame: 1 year
Change from baseline in cognitive function as assessed by a brief battery of cognitive tests.
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2019.
- Background: PubMed 22525427Ziehn MO, Avedisian AA, Dervin SM, O'Dell TJ, Voskuhl RR. Estriol preserves synaptic transmission in the hippocampus during autoimmune demyelinating disease. Lab Invest. 2012 Aug;92(8):1234-45. doi: 10.1038/labinvest.2012.76. Epub 2012 Apr 23.
- 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.
- Background: PubMed 27302354Voskuhl R, Wang H, Elashoff RM. Why use sex hormones in relapsing-remitting multiple sclerosis? - Authors' reply. Lancet Neurol. 2016 Jul;15(8):790-791. doi: 10.1016/S1474-4422(16)00129-0. No abstract available.
- Background: PubMed 27605172Voskuhl R, Patti F. Hormone replacement in menopausal women with multiple sclerosis: Looking back, thinking forward. Neurology. 2016 Oct 4;87(14):1430-1431. doi: 10.1212/WNL.0000000000003189. Epub 2016 Sep 7. No abstract available.
- Background: PubMed 27136400Voskuhl R. Rebound Relapses After Ceasing Another Disease-Modifying Treatment in Patients With Multiple Sclerosis: Are There Lessons to Be Learned? JAMA Neurol. 2016 Jul 1;73(7):775-6. doi: 10.1001/jamaneurol.2016.0934. No abstract available.
- Background: PubMed 27771018Itoh N, Kim R, Peng M, DiFilippo E, Johnsonbaugh H, MacKenzie-Graham A, Voskuhl RR. Bedside to bench to bedside research: Estrogen receptor beta ligand as a candidate neuroprotective treatment for multiple sclerosis. J Neuroimmunol. 2017 Mar 15;304:63-71. doi: 10.1016/j.jneuroim.2016.09.017. Epub 2016 Oct 3.
- Background: PubMed 29228214Kim RY, Mangu D, Hoffman AS, Kavosh R, Jung E, Itoh N, Voskuhl R. Oestrogen receptor β ligand acts on CD11c+ cells to mediate protection in experimental autoimmune encephalomyelitis. Brain. 2018 Jan 1;141(1):132-147. doi: 10.1093/brain/awx315.
- Background: PubMed 30144306MacKenzie-Graham A, Brook J, Kurth F, Itoh Y, Meyer C, Montag MJ, Wang HJ, Elashoff R, Voskuhl RR. Estriol-mediated neuroprotection in multiple sclerosis localized by voxel-based morphometry. Brain Behav. 2018 Sep;8(9):e01086. doi: 10.1002/brb3.1086. Epub 2018 Aug 24.
- Background: PubMed 31040210Voskuhl RR, Itoh N, Tassoni A, Matsukawa MA, Ren E, Tse V, Jang E, Suen TT, Itoh Y. Gene expression in oligodendrocytes during remyelination reveals cholesterol homeostasis as a therapeutic target in multiple sclerosis. Proc Natl Acad Sci U S A. 2019 May 14;116(20):10130-10139. doi: 10.1073/pnas.1821306116. Epub 2019 Apr 30.
- Background: PubMed 30058469Voskuhl R. It is time to conduct phase 3 clinical trials of sex hormones in MS - Yes. Mult Scler. 2018 Oct;24(11):1413-1415. doi: 10.1177/1352458518768764. Epub 2018 Jul 30. No abstract available.
- Background: PubMed 28766273Voskuhl R, Momtazee C. Pregnancy: Effect on Multiple Sclerosis, Treatment Considerations, and Breastfeeding. Neurotherapeutics. 2017 Oct;14(4):974-984. doi: 10.1007/s13311-017-0562-7.
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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.
Rhonda Voskuhl, M.D. principal investigator
University of California, Los Angeles
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing estriol and Norethindrone in people with Relapsing-remitting Multiple Sclerosis and Secondary-progressive Multiple Sclerosis, run by University of California, Los Angeles at 4 sites 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 10 inclusion and 17 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: status not confirmed, as of the sponsor's last update on 6 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mike Montag, M.S. ((310)206-2176, MMontag@mednet.ucla.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in cognitive function assessed by Paced Serial Addition Test (PASAT). (time frame: 1 year). 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 NCT01466114, which also lists 11 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 6 Nov 2019.