Recruiting
Phase 2

Estriol

Sponsor:

UCLA

Code:

NCT01466114

Conditions

Relapsing-remitting Multiple Sclerosis

Secondary-progressive Multiple Sclerosis

Primary-progressive Multiple Sclerosis

Eligibility Criteria

Sex: Female

Age: 18 - 55

Healthy Volunteers: Not accepted

Interventions

estriol

Placebo

Norethindrone

Progestin Placebo

Study Details

Brief 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. 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.

Conditions

Relapsing-remitting Multiple Sclerosis

Secondary-progressive Multiple Sclerosis

Primary-progressive Multiple Sclerosis

Study ID

NCT01466114

Start date

Oct, 2011

Status verified date

Nov, 2019

Completion date

Apr, 2022

Anticipated

Primary completion date

Dec, 2021

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Female

Age: 18 - 55

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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.
  • 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:

  • 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.
  • 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").

Study Design

Enrollment

64 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Group A: Estriol

Standard MS Treatment + Estriol

placebo comparator: Group B: Placebo

Standard MS Treatment + Placebo

Interventions

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.

Primary outcome measure

  • Change from baseline in cognitive function assessed by Paced Serial Addition Test (PASAT). [ Time Frame: 1 year ]

Central Contacts and Locations

Central contacts

Mike Montag, M.S.

(310)206-2176MMontag@mednet.ucla.edu

Locations

University of California Los Angeles

Recruiting

Los Angeles, California, United States, 90095

Contacts

Mike Montag, M.S.

310-206-2176MMontag@mednet.ucla.edu

More Information

Sponsor

University of California, Los Angeles

Last update posted

Nov 6, 2019

Last verified

Nov, 2019

Keywords

  • multiple sclerosis
  • MS
  • relapsing remitting multiple sclerosis
  • RRMS
  • secondary progressive multiple sclerosis
  • SPMS
  • primary progressive multiple sclerosis
  • estrogen
  • estriol

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by University of California, Los Angeles on 2019-11-06.