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A Combination Trial of Copaxone Plus Estriol in Relapsing Remitting Multiple Sclerosis (RRMS) (Estriol in 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
Western Institute for Biomedical Research, Salt Lake City, UT
Johns Hopkins University
University of Kansas
University of Minnesota - Clinical and Translational Science Institute
Mayo Clinic
University of Colorado, Aurora
University of New Mexico
University of Pennsylvania
Dartmouth Medical School, Lebanon, NH
National Multiple Sclerosis Society
Synthetic Biologics, Ann Arnor, MI
Information provided by (Responsible Party):
Rhonda Voskuhl, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT00451204
First received: March 22, 2007
Last updated: May 15, 2014
Last verified: May 2014

March 22, 2007
May 15, 2014
March 2007
January 2014   (final data collection date for primary outcome measure)
Relapse Rate [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Relapse Rate
Complete list of historical versions of study NCT00451204 on ClinicalTrials.gov Archive Site
  • severity of "Relapse" as assessed by degree of worsening of Expanded Disability Status Scale (EDSS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Proportion of subjects with confirmed progression in Expanded Disability Status Scale (EDSS) (at least 1.0 point for at least 6 months on two exams) between baseline and conclusion [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Expanded Disability Status Scale (EDSS) progression from baseline at conclusion [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Improvement in Paced Serial Addition Test (PASAT) scores between baseline and conclusion [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Improvement in 7-24 Spatial Recall test scores between baseline and conclusion [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Improvement in Selective Reminding Test scores between baseline and conclusion [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Brain MRI enhancing lesions [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Time to first relapse [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The number of days to relapse from month 0 will be assessed in each treatment group
  • Relapse Related Secondary
  • "Relapse Event" Rate
  • time to first "Relapse"
  • time to first "Relapse Event"
  • proportion of subjects "Relapse" free at each year
  • proportion of subjects "Relapse Event" free at each year
  • number of "Relapses" per subject
  • number of "Relapse Events" per subject
  • severity of "Relapse" as assessed by degree of worsening of EDSS
  • severity of "Relapse Event" as assessed by degree of worsening of EDSS
  • severity of "Relapse" as assessed by degree of worsening of MSFC.
  • severity of "Relapse Event" as assessed by degree of worsening of MSFC.
  • number of times IV solumedrol was administered per subject for treatment of "Relapses."
  • number of times IV solumedrol was administered per subject for treatment of "Relapse Events."
  • Disability Related Secondary
  • Proportion of subjects with confirmed progression in EDSS (at least 1.0 point for at least 6 months on two exams) between baseline and conclusion
  • EDSS progression from baseline at conclusion
  • MSFC progression from baseline at conclusion
  • Improvement in PASAT scores between baseline and conclusion
  • Improvement in 7-24 Spatial Recall test scores between baseline and conclusion
  • Improvement in Selective Reminding Test scores between baseline and conclusion
Not Provided
Not Provided
 
A Combination Trial of Copaxone Plus Estriol in Relapsing Remitting Multiple Sclerosis (RRMS)
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.

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. Secondary and exploratory outcomes will include disability measures (MSFC, EDSS, Quality of Life, Fatigue and Depression testing) and MRI as a biomarker (white matter enhancing lesion number and volume, T2 lesion volume). Safety measures (blood tests and gynecologic evaluations) will also be followed. The overall goal of this study will be the development of an oral anti-inflammatory treatment, estriol, for RRMS.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Relapsing Remitting Multiple Sclerosis
  • Drug: Estriol
    Estriol 8 mg capsule, once per day, duration of treatment is 2 years
    Other Names:
    • E3
    • estrogen
  • Drug: Placebo
    Placebo capsule, once a day, treatment duration is 2 years
  • Active Comparator: 1
    Estriol Pills plus Copaxone injections
    Intervention: Drug: Estriol
  • Placebo Comparator: 2
    Placebo pills plus Copaxone injections
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
158
January 2014
January 2014   (final data collection date for primary outcome measure)

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
Female
18 Years to 50 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00451204
RO1-NS051591, NIH grant RO1-NS051591, NMSS grant RG 3915
Yes
Rhonda Voskuhl, University of California, Los Angeles
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
  • Western Institute for Biomedical Research, Salt Lake City, UT
  • Johns Hopkins University
  • University of Kansas
  • University of Minnesota - Clinical and Translational Science Institute
  • Mayo Clinic
  • University of Colorado, Aurora
  • University of New Mexico
  • University of Pennsylvania
  • Dartmouth Medical School, Lebanon, NH
  • National Multiple Sclerosis Society
  • National Institutes of Health (NIH)
  • Synthetic Biologics, Ann Arnor, MI
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: Angela Bates, 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 - Clinical and Translational Science Institute
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: Enrico Lallana, M.D. Dartmouth University, Lebanon, NH
University of California, Los Angeles
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP