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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
History of Changes

March 22, 2007
May 10, 2016
March 2007
July 2014   (final data collection date for primary outcome measure)
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.
Relapse Rate
Complete list of historical versions of study NCT00451204 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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
  • 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.
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. 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.
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
    Other Name: "sugar pill"
  • Drug: Copaxone
    Injection, once a day, all subjects
    Other Name: glatiramer acetate
  • 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.
    Interventions:
    • Drug: Estriol
    • Drug: Copaxone
  • 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.
    Interventions:
    • Drug: Placebo
    • Drug: Copaxone

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
158
July 2014
July 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   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00451204
R01NS051591, R01NS051591, RG3915
Yes
Yes
Investigators interested in further research using the data should contact Dr. Voskuhl with proposed plans and request.
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
  • 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)
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, 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
University of California, Los Angeles
May 2016

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