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

NCT ID: NCT00451204

Last Updated: 2016-06-16

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

158 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-03-31

Study Completion Date

2014-07-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Relapsing Remitting Multiple Sclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Estriol

Intervention Type DRUG

Estriol 8 mg capsule, once per day, duration of treatment is 2 years

Copaxone

Intervention Type DRUG

Injection, once a day, all subjects

Placebo plus Copaxone injections QD

Placebo Capsules (daily) plus Copaxone injections (daily). A second placebo capsule given for 2 weeks every 3 months.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo capsule, once a day, treatment duration is 2 years

Copaxone

Intervention Type DRUG

Injection, once a day, all subjects

Interventions

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Estriol

Estriol 8 mg capsule, once per day, duration of treatment is 2 years

Intervention Type DRUG

Placebo

Placebo capsule, once a day, treatment duration is 2 years

Intervention Type DRUG

Copaxone

Injection, once a day, all subjects

Intervention Type DRUG

Other Intervention Names

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E3 estrogen "sugar pill" glatiramer acetate

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Washington University School of Medicine

OTHER

Sponsor Role collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role collaborator

Ohio State University

OTHER

Sponsor Role collaborator

University of Medicine and Dentistry of New Jersey

OTHER

Sponsor Role collaborator

University of Chicago

OTHER

Sponsor Role collaborator

University of Utah

OTHER

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role collaborator

University of Kansas Medical Center

OTHER

Sponsor Role collaborator

University of Minnesota

OTHER

Sponsor Role collaborator

Mayo Clinic

OTHER

Sponsor Role collaborator

University of Colorado, Denver

OTHER

Sponsor Role collaborator

University of New Mexico

OTHER

Sponsor Role collaborator

University of Pennsylvania

OTHER

Sponsor Role collaborator

Dartmouth-Hitchcock Medical Center

OTHER

Sponsor Role collaborator

National Multiple Sclerosis Society

OTHER

Sponsor Role collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

University of California, Los Angeles

OTHER

Sponsor Role lead

Responsible Party

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Rhonda Voskuhl

Professor, Department of Neurology; Director Multiple Sclerosis Program

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Rhonda Voskuhl, M.D.

Role: STUDY_DIRECTOR

University of California, Los Angeles (UCLA), Los Angeles, CA

Anne Cross, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University, Saint Louis, MO

Elliot Frohman, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Texas, Southwestern, Dallas, TX

Suhayl Dhib-Jalbut, M.D.

Role: PRINCIPAL_INVESTIGATOR

Robert Wood Johnson Medical School, UMDNJ, New Brunswick, NJ

Michael Racke, M.D.

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Anthony Reder, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Chicago

John Rose, M.D.

Role: PRINCIPAL_INVESTIGATOR

Western Institute for Biomedical Research, Salt Lake City, UT

Barbara Giesser, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles (UCLA), Los Angeles, CA

John Ratchford, M.D.

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins, Baltimore, MD

Sharon Lynch, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Kansas

Gareth Parry, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Dean Wingerchuk, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

John Corboy, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Corey Ford, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of New Mexico, Albuquerque

Dina Jacobs, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Lloyd Kasper, M.D.

Role: PRINCIPAL_INVESTIGATOR

Dartmouth University, Lebanon, NH

Locations

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Mayo Clinic

Scottsdale, Arizona, United States

Site Status

University of California, Los Angeles

Los Angeles, California, United States

Site Status

University of Colorado

Aurora, Colorado, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

University of Kansas

Kansas City, Kansas, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

Dartmouth Medical School

Lebanon, New Hampshire, United States

Site Status

UMDNJ-Robert Wood Johnson Medical Center

New Brunswick, New Jersey, United States

Site Status

University of New Mexico

Albuquerque, New Mexico, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

University of Texas Southwestern

Dallas, Texas, United States

Site Status

Western Institute for Biomedical Research

Salt Lake City, Utah, United States

Site Status

Montreal Neurological Institute

Montreal, , Canada

Site Status

Countries

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United States Canada

References

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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. doi: 10.1002/ana.10301.

Reference Type BACKGROUND
PMID: 12325070 (View on PubMed)

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. doi: 10.4049/jimmunol.171.11.6267.

Reference Type BACKGROUND
PMID: 14634144 (View on PubMed)

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. doi: 10.1523/JNEUROSCI.0453-06.2006.

Reference Type BACKGROUND
PMID: 16793889 (View on PubMed)

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. doi: 10.1073/pnas.0703783104. Epub 2007 Sep 4.

Reference Type BACKGROUND
PMID: 17785421 (View on PubMed)

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. doi: 10.1001/archneur.64.5.683.

Reference Type BACKGROUND
PMID: 17502467 (View on PubMed)

Gold SM, Sasidhar MV, Morales LB, Du S, Sicotte NL, Tiwari-Woodruff SK, Voskuhl RR. Estrogen treatment decreases matrix metalloproteinase (MMP)-9 in autoimmune demyelinating disease through estrogen receptor alpha (ERalpha). Lab Invest. 2009 Oct;89(10):1076-83. doi: 10.1038/labinvest.2009.79. Epub 2009 Aug 10.

Reference Type BACKGROUND
PMID: 19668239 (View on PubMed)

Ziehn MO, Avedisian AA, Dervin SM, O'Dell TJ, Voskuhl RR. Estriol preserves synaptic transmission in the hippocampus during autoimmune demyelinating disease. Lab Invest. 2012 Aug;92(8):1234-45. doi: 10.1038/labinvest.2012.76. Epub 2012 Apr 23.

Reference Type BACKGROUND
PMID: 22525427 (View on PubMed)

Spence RD, Hamby ME, Umeda E, Itoh N, Du S, Wisdom AJ, Cao Y, Bondar G, Lam J, Ao Y, Sandoval F, Suriany S, Sofroniew MV, Voskuhl RR. Neuroprotection mediated through estrogen receptor-alpha in astrocytes. Proc Natl Acad Sci U S A. 2011 May 24;108(21):8867-72. doi: 10.1073/pnas.1103833108. Epub 2011 May 9.

Reference Type BACKGROUND
PMID: 21555578 (View on PubMed)

Voskuhl RR, Wang H, Wu TC, Sicotte NL, Nakamura K, Kurth F, Itoh N, Bardens J, Bernard JT, Corboy JR, Cross AH, Dhib-Jalbut S, Ford CC, Frohman EM, Giesser B, Jacobs D, Kasper LH, Lynch S, Parry G, Racke MK, Reder AT, Rose J, Wingerchuk DM, MacKenzie-Graham AJ, Arnold DL, Tseng CH, Elashoff R. Estriol combined with glatiramer acetate for women with relapsing-remitting multiple sclerosis: a randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2016 Jan;15(1):35-46. doi: 10.1016/S1474-4422(15)00322-1. Epub 2015 Nov 29.

Reference Type RESULT
PMID: 26621682 (View on PubMed)

Other Identifiers

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R01NS051591

Identifier Type: NIH

Identifier Source: secondary_id

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RG3915

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

R01NS051591

Identifier Type: NIH

Identifier Source: org_study_id

View Link

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