Estriol Treatment in Multiple Sclerosis (MS): Effect on Cognition
NCT ID: NCT01466114
Last Updated: 2019-11-06
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
UNKNOWN
PHASE2
64 participants
INTERVENTIONAL
2011-10-31
2022-04-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
A Combination Trial of Copaxone Plus Estriol in Relapsing Remitting Multiple Sclerosis (RRMS)
NCT00451204
MS-SMART: Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial
NCT01910259
Study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients With Multiple Sclerosis
NCT00134563
Multiple Sclerosis-Simvastatin Trial 2
NCT03387670
The Effects of Erythropoietin on Clinical Disability and Brain Pathology in Patients With Progressive Multiple Sclerosis
NCT01144117
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Group A: Estriol
Standard MS Treatment + Estriol
estriol
4 capsules of 2 mg (total of 8 mg) PO QD
Norethindrone
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.
Group B: Placebo
Standard MS Treatment + Placebo
Placebo
4 capsules PO QD
Progestin Placebo
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.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
estriol
4 capsules of 2 mg (total of 8 mg) PO QD
Placebo
4 capsules PO QD
Norethindrone
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 Placebo
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.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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.
* 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).
Exclusion Criteria
* 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.
* 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").
18 Years
55 Years
FEMALE
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
University of California, Los Angeles
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Rhonda Voskuhl
Professor, Department of Neurology; Director Multiple Sclerosis Program
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Rhonda Voskuhl, M.D.
Role: PRINCIPAL_INVESTIGATOR
University of California, Los Angeles
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
University of California Los Angeles
Los Angeles, California, United States
The University of Colorado Denver
Aurora, Colorado, United States
The University of New Mexico
Albuquerque, New Mexico, United States
The University of Pennsylvania
Philadelphia, Pennsylvania, United States
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
References
Explore related publications, articles, or registry entries linked to this study.
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.
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.
Voskuhl 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.
Voskuhl 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.
Voskuhl 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.
Itoh 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.
Kim 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.
MacKenzie-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.
Voskuhl 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.
Voskuhl 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.
Voskuhl 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.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
11-002055
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.