Trial record 2 of 2 for:    ms, estriol

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

This study has been completed.
Sponsor:
Collaborators:
Washington University School of Medicine
University of Texas Southwestern Medical Center
Ohio State University
University of Medicine and Dentistry of New Jersey
University of Chicago
University of Utah
Johns Hopkins University
University of Kansas Medical Center
University of Minnesota, MN
Mayo Clinic
University of Colorado, Aurora
University of New Mexico
University of Pennsylvania
Dartmouth-Hitchcock Medical Center
National Multiple Sclerosis Society
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Rhonda Voskuhl, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT00451204
First received: March 22, 2007
Last updated: May 10, 2016
Last verified: May 2016
  Purpose
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.

Condition Intervention Phase
Relapsing Remitting Multiple Sclerosis
Drug: Estriol
Drug: Placebo
Drug: Copaxone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Combination Trial of Copaxone Plus Estriol in RRMS

Resource links provided by NLM:


Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:
  • Confirmed Relapse, Annualized Relapse Rate [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Relapse Event, Annualized Relapse Rate [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Met all criteria for relapse except not confirmed to have increase in EDSS by an independent examiner.

  • Confirmed Relapse, Probability of First Relapse [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Relapse Event, Probability of First Relapse Event [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Confirmed Relapse, Annualized Relapse Rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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.

  • Relapse Event, Annualized Relapse Rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Met all criteria for relapse except not confirmed to have increase in EDSS by an independent examiner.


Enrollment: 158
Study Start Date: March 2007
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • E3
  • estrogen
Drug: Copaxone
Injection, once a day, all subjects
Other Name: 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: Placebo
Placebo capsule, once a day, treatment duration is 2 years
Other Name: "sugar pill"
Drug: Copaxone
Injection, once a day, all subjects
Other Name: glatiramer acetate

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.
  Eligibility

Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00451204

Locations
United States, Arizona
Mayo Clinic
Scottsdale, Arizona, United States, 85259
United States, California
University of California, Los Angeles
Los Angeles, California, United States, 90095
United States, Colorado
University of Colorado
Aurora, Colorado, United States, 80045
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Kansas
University of Kansas
Kansas City, Kansas, United States, 66160
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287-6965
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Washington University
Saint Louis, Missouri, United States, 63110
United States, New Hampshire
Dartmouth Medical School
Lebanon, New Hampshire, United States, 03765
United States, New Jersey
UMDNJ-Robert Wood Johnson Medical Center
New Brunswick, New Jersey, United States, 08901
United States, New Mexico
University of New Mexico
Albuquerque, New Mexico, United States, 87131
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43221
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
University of Texas Southwestern
Dallas, Texas, United States, 75390-8575
United States, Utah
Western Institute for Biomedical Research
Salt Lake City, Utah, United States, 84158
Canada
Montreal Neurological Institute
Montreal, Canada
Sponsors and Collaborators
University of California, Los Angeles
Washington University School of Medicine
University of Texas Southwestern Medical Center
Ohio State University
University of Medicine and Dentistry of New Jersey
University of Chicago
University of Utah
Johns Hopkins University
University of Kansas Medical Center
University of Minnesota, MN
Mayo Clinic
University of Colorado, Aurora
University of New Mexico
University of Pennsylvania
Dartmouth-Hitchcock Medical Center
National Multiple Sclerosis Society
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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 Medical Center
Principal Investigator: Gareth Parry, M.D. University of Minnesota, MN
Principal Investigator: Dean Wingerchuk, M.D. Mayo Clinic
Principal Investigator: John Corboy, M.D. University of Colorado, Aurora
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
  More Information

Publications:

Responsible Party: Rhonda Voskuhl, Professor, Department of Neurology; Director Multiple Sclerosis Program, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT00451204     History of Changes
Other Study ID Numbers: RO1-NS051591  R01NS051591  RG3915 
Study First Received: March 22, 2007
Results First Received: January 20, 2016
Last Updated: May 10, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Investigators interested in further research using the data should contact Dr. Voskuhl with proposed plans and request.

Keywords provided by University of California, Los Angeles:
Multiple sclerosis
estrogen
estriol
progesterone

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Estrogens
Glatiramer Acetate
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Adjuvants, Immunologic
Immunologic Factors
Immunosuppressive Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 24, 2016