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

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
158

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Canada
      • Montreal, Canada
        • Montreal Neurological Institute
  • United States
    • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Drug: Estriol
Estriol 8 mg capsule, once per day, duration of treatment is 2 years
Other Names:
  • estrogen
  • E3
Drug: Copaxone
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.
Drug: Copaxone
Injection, once a day, all subjects
Other Names:
  • glatiramer acetate
Drug: Placebo
Placebo capsule, once a day, treatment duration is 2 years
Other Names:
  • "sugar pill"

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
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.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of California, Los Angeles

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Johns Hopkins University
University of Colorado, Denver
Mayo Clinic
University of Pennsylvania
Washington University School of Medicine
University of Chicago
National Institute of Neurological Disorders and Stroke (NINDS)
National Institutes of Health (NIH)
Dartmouth-Hitchcock Medical Center
Ohio State University
University of Kansas Medical Center
University of Minnesota
University of Texas Southwestern Medical Center
University of Utah
University of New Mexico
National Multiple Sclerosis Society
University of Medicine and Dentistry of New Jersey

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 22, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 22, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 23, 2007

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 16, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 10, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • R01NS051591 (U.S. NIH Grant/Contract)
  • RG3915 (Other Grant/Funding Number: NMSS)

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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