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

Sponsor:	University of California, Los Angeles
Collaborators:	Washington University School of Medicine University of Texas Southwestern Medical Center Ohio State University University of Medicine and Dentistry 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) Adeona Pharmaceuticals, Ann Arnor, MI
Information provided by:	University of California, Los Angeles
ClinicalTrials.gov Identifier:	NCT00451204

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	Phase II

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:

MedlinePlus related topics: Multiple Sclerosis

Drug Information available for: Estriol Copolymer 1 16-Epiestriol

U.S. FDA Resources

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

Primary Outcome Measures:

Relapse Rate [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

severity of "Relapse" as assessed by degree of worsening of Expanded Disability Status Scale (EDSS) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
severity of "Relapse" as assessed by degree of worsening of Multiple Sclerosis Functional Composite (MSFC) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
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: Yes ]
Expanded Disability Status Scale (EDSS) progression from baseline at conclusion [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Multiple Sclerosis Functional Composite (MSFC) progression from baseline at conclusion [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
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: Yes ]
Brain atrophy on MRI [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	150
Study Start Date:	March 2007
Estimated Study Completion Date:	January 2014
Estimated Primary Completion Date:	January 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Estriol Pills plus Copaxone injections	Drug: Estriol Estriol 8 mg capsule, once per day, duration of treatment is 2 years Other Names: E3 estrogen
Placebo Comparator: 2 Placebo pills plus Copaxone injections	Drug: Placebo Placebo capsule, once a day, treatment duration is 2 years

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. 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.

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
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

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

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 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)

Adeona Pharmaceuticals, Ann Arnor, MI

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:	Ardith Courtney, D.O.	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

More Information

Additional Information:

National Multiple Sclerosis Society announcement of this multicenter trial This link exits the ClinicalTrials.gov site

Publications:

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.

Responsible Party:	Rhonda Voskuhl, M.D., University of California, Los Angeles
ClinicalTrials.gov Identifier:	NCT00451204 History of Changes
Other Study ID Numbers:	RO1-NS051591, NIH grant RO1-NS051591, NMSS grant RG 3915
Study First Received:	March 22, 2007
Last Updated:	January 23, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of California, Los Angeles:

Multiple sclerosis
estrogen
estriol
progesterone

Additional relevant MeSH terms:

Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes

Estrogens
Copolymer 1
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Adjuvants, Immunologic
Immunologic Factors
Immunosuppressive Agents

ClinicalTrials.gov processed this record on February 09, 2012