| March 22, 2007 |
| May 4, 2009 |
| March 2007 |
| April 2012 (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 EDSS [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- severity of "Relapse" as assessed by degree of worsening of MSFC. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- 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 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- EDSS progression from baseline at conclusion [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- MSFC progression from baseline at conclusion [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Improvement in 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: Yes ]
- Brain atrophy on MRI [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
|
- 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
|
| |
| 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 outcomes will include disability measures (MSFC, EDSS, Quality of Life, Fatigue and Depression testing) and a surrogate marker for disability (cerebral MRI for whole brain volume, gray matter atrophy and T1 holes). 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. |
| Phase II, Phase III |
| Interventional |
| Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Efficacy Study |
| Relapsing Remitting Multiple Sclerosis |
- Drug: Estriol
- Drug: Placebo
|
- Active Comparator: Estriol Pills plus Copaxone injections
- Placebo Comparator: Placebo pills plus Copaxone injections
|
- Sicotte NL, Liva SM, Klutch R, Pfeiffer P, Bouvier S, Odesa S, Wu TC, Voskuhl RR. Treatment of multiple sclerosis with the pregnancy hormone estriol. Ann Neurol. 2002 Oct;52(4):421-8.
- Soldan SS, Alvarez Retuerto AI, Sicotte NL, Voskuhl RR. Immune modulation in multiple sclerosis patients treated with the pregnancy hormone estriol. J Immunol. 2003 Dec 1;171(11):6267-74.
- Morales LB, Loo KK, Liu HB, Peterson C, Tiwari-Woodruff S, Voskuhl RR. Treatment with an estrogen receptor alpha ligand is neuroprotective in experimental autoimmune encephalomyelitis. J Neurosci. 2006 Jun 21;26(25):6823-33.
- Tiwari-Woodruff S, Morales LB, Lee R, Voskuhl RR. Differential neuroprotective and antiinflammatory effects of estrogen receptor (ER)alpha and ERbeta ligand treatment. Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14813-8. Epub 2007 Sep 4.
- Sicotte NL, Giesser BS, Tandon V, Klutch R, Steiner B, Drain AE, Shattuck DW, Hull L, Wang HJ, Elashoff RM, Swerdloff RS, Voskuhl RR. Testosterone treatment in multiple sclerosis: a pilot study. Arch Neurol. 2007 May;64(5):683-8.
|
| |
| Recruiting |
| 150 |
| July 2012 |
| April 2012 (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 |
|
|
| United States |
| |
| NCT00451204 |
| Rhonda Voskuhl, M.D., University of California, Los Angeles |
| RO1-NS051591, NIH grant RO1-NS051591, NMSS grant RG 3915 |
| University of California, Los Angeles |
- University of California, Los Angeles, Los Angeles, CA
- Washington University School of Medicine, Saint Louis, MO
- University of Texas Southwestern Medical Center
- Ohio State University, Columbus, OH
- University of Medicine and Dentistry New Jersey, New Brunswick, NJ
- University of Chicago
- Western Institute for Biomedical Research, Salt Lake City, UT
- Johns Hopkins University
- Columbia University
- University of Kansas, Kansas City, Kansas
- University of Minnesota, Minneapolis, MN
- Mayo Clinic, Scottsdale, AZ
- University of Colorado, Aurora, CO
- University of New Mexico, Albuquerque, NM
- University of Pennsylvania, Philadelphia, PA
- Dartmouth Medical School, Lebanon, NH
- National Multiple Sclerosis Society
- National Institutes of Health (NIH)
- Adeona Pharmaceuticals, Inc.
|
| 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: |
Deborah J Lynn, M.D. |
Ohio State University, Columbus, OH |
|
| 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: |
Peter Calabresi, M.D. |
Johns Hopkins, Baltimore, MD |
|
| Principal Investigator: |
Sharon Lynch, M.D. |
University of Kansas, Kansas City, Kansas |
|
| Principal Investigator: |
Gareth Parry, M.D. |
University of Minnesota, Minneapolis, MN |
|
| Principal Investigator: |
Mark Tullman, M.D. |
Columbia University |
|
| Principal Investigator: |
Dean Wingerchuk, M.D. |
Mayo Clinic, Scottsdale, AZ |
|
| Principal Investigator: |
John Corboy, M.D. |
University of Colorado, Aurora, CO |
|
| Principal Investigator: |
Corey Ford, M.D. |
University of New Mexico, Albuquerque |
|
| Principal Investigator: |
Dina Jacobs, M.D. |
University of Pennsylvania, Philadelphia, PA |
|
| Principal Investigator: |
Lloyd Kasper, M.D. |
Dartmouth University, Lebanon, NH |
|
|
| University of California, Los Angeles |
| May 2009 |