A Combination Trial of Copaxone Plus Estriol in Relapsing Remitting Multiple Sclerosis (RRMS) (Estriol-MS)

May 10, 2016 updated by: Rhonda Voskuhl, University of California, Los Angeles

A Combination Trial of Copaxone Plus Estriol in RRMS

This is a double-blinded, placebo controlled study of estriol pills versus placebo pills in relapsing remitting multiple sclerosis. The study treatment will be an added on to Copaxone injections in all subjects. The primary outcome measure is a reduction in relapses.

Study Overview

Detailed Description

Multiple sclerosis (MS) relapses are known to be significantly decreased during pregnancy. This proposal will establish whether oral treatment with estriol, the major estrogen of pregnancy, induces a decrease in relapses in relapsing remitting multiple sclerosis (RRMS) subjects when used in combination with injectable Copaxone. Previously, in a pilot study, it has been demonstrated that treatment of RRMS subjects with oral estriol for six months resulted in a significant reduction in gadolinium enhancing lesions on serial brain MRIs (Annals of Neurology, 2002; 52:421-428) and caused a favorable shift in immune responses (Journal of Immunology, 2003; 171:6267-6274). This is an add-on study aiming to extend these previous findings by treating longer and focusing on clinical outcomes. The combination of Copaxone injection plus estriol pill (8 mg per day) will be compared to Copaxone injection plus placebo pill in a double blind trial. The duration of treatment will be two years and the primary outcome measure will be relapse rate. Other outcomes will include disability measures and brain MRI outcomes. Safety measures (blood tests and gynecologic evaluations) will also be followed and correlations will be made between serum estriol levels with efficacy and safety. The overall goal of this study will be the development of a new oral treatment, estriol, for RRMS.

Study Type

Interventional

Enrollment (Actual)

158

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Montreal, Canada
        • Montreal Neurological Institute
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic
    • California
      • Los Angeles, California, United States, 90095
        • University of California, Los Angeles
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas
    • Maryland
      • Baltimore, Maryland, United States, 21287-6965
        • Johns Hopkins University
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03765
        • Dartmouth Medical School
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • UMDNJ-Robert Wood Johnson Medical Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • University of New Mexico
    • Ohio
      • Columbus, Ohio, United States, 43221
        • Ohio State University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
    • Texas
      • Dallas, Texas, United States, 75390-8575
        • University of Texas Southwestern
    • Utah
      • Salt Lake City, Utah, United States, 84158
        • Western Institute for Biomedical Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Diagnosis of relapsing remitting multiple sclerosis
  • At least one relapse in the last two years

Exclusion Criteria:

  • Patients treated in the past with total lymphoid irradiation, monoclonal antibody, T cell vaccination, cladribine, bone marrow transplantation, azathioprine, cyclophosphamide, methotrexate, mitoxantrone, cyclosporin or Tysabri
  • Clinically significant diseases other than multiple sclerosis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Estriol plus Copaxone injections QD
Estriol Capsules (daily) plus Copaxone injections (daily). Progestin capsules given for 2 weeks every 3 months to avoid unopposed estrogens.
Estriol 8 mg capsule, once per day, duration of treatment is 2 years
Other Names:
  • estrogen
  • E3
Injection, once a day, all subjects
Other Names:
  • glatiramer acetate
Placebo Comparator: Placebo plus Copaxone injections QD
Placebo Capsules (daily) plus Copaxone injections (daily). A second placebo capsule given for 2 weeks every 3 months.
Injection, once a day, all subjects
Other Names:
  • glatiramer acetate
Placebo capsule, once a day, treatment duration is 2 years
Other Names:
  • "sugar pill"

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Confirmed Relapse, Annualized Relapse Rate
Time Frame: 24 months
A confirmed relapse was defined as new neurological symptoms or worsening of pre-existing symptoms, lasting at least 48 hours in a subject who had been neurologically stable or improving in the previous 30 days, accompanied by objective change in the neurological examination (worsening of 0.5 points on the EDSS or worsening by 1.0 or more points on the pyramidal, cerebellar, brainstem or visual functional system scores), not due to fatigue alone and not associated with fever or infection.
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relapse Event, Annualized Relapse Rate
Time Frame: 24 months
Met all criteria for relapse except not confirmed to have increase in EDSS by an independent examiner.
24 months
Confirmed Relapse, Probability of First Relapse
Time Frame: 24 months
24 months
Relapse Event, Probability of First Relapse Event
Time Frame: 24 months
24 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Confirmed Relapse, Annualized Relapse Rate
Time Frame: 12 months
A confirmed relapse was defined as new neurological symptoms or worsening of pre-existing symptoms, lasting at least 48 hours in a subject who had been neurologically stable or improving in the previous 30 days, accompanied by objective change in the neurological examination (worsening of 0.5 points on the EDSS or worsening by 1.0 or more points on the pyramidal, cerebellar, brainstem or visual functional system scores), not due to fatigue alone and not associated with fever or infection.
12 months
Relapse Event, Annualized Relapse Rate
Time Frame: 12 months
Met all criteria for relapse except not confirmed to have increase in EDSS by an independent examiner.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Rhonda Voskuhl, M.D., University of California, Los Angeles (UCLA), Los Angeles, CA
  • Principal Investigator: Anne Cross, M.D., Washington University, Saint Louis, MO
  • Principal Investigator: Elliot Frohman, M.D., University of Texas, Southwestern, Dallas, TX
  • Principal Investigator: Suhayl Dhib-Jalbut, M.D., Robert Wood Johnson Medical School, UMDNJ, New Brunswick, NJ
  • Principal Investigator: Michael Racke, M.D., Ohio State University
  • Principal Investigator: Anthony Reder, M.D., University of Chicago
  • Principal Investigator: John Rose, M.D., Western Institute for Biomedical Research, Salt Lake City, UT
  • Principal Investigator: Barbara Giesser, M.D., University of California, Los Angeles (UCLA), Los Angeles, CA
  • Principal Investigator: John Ratchford, M.D., Johns Hopkins, Baltimore, MD
  • Principal Investigator: Sharon Lynch, M.D., University of Kansas
  • Principal Investigator: Gareth Parry, M.D., University of Minnesota
  • Principal Investigator: Dean Wingerchuk, M.D., Mayo Clinic
  • Principal Investigator: John Corboy, M.D., University of Colorado, Denver
  • Principal Investigator: Corey Ford, M.D., University of New Mexico, Albuquerque
  • Principal Investigator: Dina Jacobs, M.D., University of Pennsylvania
  • Principal Investigator: Lloyd Kasper, M.D., Dartmouth University, Lebanon, NH

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2007

Primary Completion (Actual)

July 1, 2014

Study Completion (Actual)

July 1, 2014

Study Registration Dates

First Submitted

March 22, 2007

First Submitted That Met QC Criteria

March 22, 2007

First Posted (Estimate)

March 23, 2007

Study Record Updates

Last Update Posted (Estimate)

June 16, 2016

Last Update Submitted That Met QC Criteria

May 10, 2016

Last Verified

May 1, 2016

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Investigators interested in further research using the data should contact Dr. Voskuhl with proposed plans and request.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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