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

Sponsors and Collaborators:	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, Baltimore, Maryland 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.
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 Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Efficacy Study
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 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 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 ]

Estimated Enrollment:	150
Study Start Date:	March 2007
Estimated Study Completion Date:	July 2012
Estimated Primary Completion Date:	April 2012 (Final data collection date for primary outcome measure)

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

Contacts

Contact: Mike Montag	(310)825-7313	MMontag@mednet.ucla.edu
Contact: Irene Tanaka	(310)794-1751	ITanaka@mednet.ucla.edu

Locations

United States, Arizona
Mayo Clinic	Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Irene Galasky, RN 480-301-6104 Galasky.Irene@mayo.edu
Principal Investigator: Dean Wingerchuk, M.D.
United States, California
University of California, Los Angeles	Recruiting
Los Angeles, California, United States, 90095
Contact: Mike Montag 310-825-7313 MMontag@mednet.ucla.edu
Contact: Irene Tanaka (310)794-1751 ITanaka@mednet.ucla.edu
Principal Investigator: Rhonda Voskuhl, M.D.
Sub-Investigator: Barbara Giesser, M.D.
Sub-Investigator: Nancy Sicotte, M.D.
Sub-Investigator: T.C. Jackson Wu, M.D., Ph.D.
Sub-Investigator: Robert Elashoff, Ph.D.
United States, Colorado
University of Colorado	Recruiting
Aurora, Colorado, United States, 80045
Contact: Caitlin Walker, RN 303-724-2198 caitlin.walker@ucdenver.edu
Contact: Caitlin Walker, RN (303) 724-2198 Caitlin.Walker@UCHSC.edu
Principal Investigator: John Corboy, M.D.
United States, Illinois
University of Chicago	Recruiting
Chicago, Illinois, United States, 60637
Contact: Mildred Valentine 773-702-9812 mvalenti@neurology.bsd.uchicago.edu
Contact: Krystal Ivy (773)834-4654 kivy@neurology.bsd.uchicago.edu
Principal Investigator: Anthony Reder, M.D.
United States, Kansas
University of Kansas	Recruiting
Kansas City, Kansas, United States, 66160
Contact: Kelly Dickerson, RN 913-588-0080 kdickerson@kumc.edu
Contact: Nicholas Levine (913) 588-0687 nlevine@kumc.edu
Principal Investigator: Sharon Lynch, M.D.
United States, Maryland
Johns Hopkins University	Recruiting
Baltimore, Maryland, United States, 21287-6965
Contact: Stephanie Syc, RN 410-502-2488 ssyc1@jhmi.edu
Contact: Kristie Albright, RN (410) 502-6867 kalbrig2@jhmi.edu
Principal Investigator: Peter Calabresi, M.D.
United States, Minnesota
University of Minnesota	Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Sarah Hilbert 612-624-5978 hilbe010@umn.edu
Contact: Susan Rolandelli, RN (612) 624 8431 rolan010@umn.edu
Principal Investigator: Gareth Parry, M.D.
United States, Missouri
Washington University	Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Debbie Kemp, R.N. 314-362-3839 kempd@wusm.wustl.edu
Contact: Nanette Bladdick (314)362-3293 bladdickn@neuro.wustl.edu
Principal Investigator: Anne Cross, M.D.
United States, New Hampshire
Dartmouth Medical School	Recruiting
Lebanon, New Hampshire, United States, 03765
Contact: Kathleen Ryan, RN 603-653-9919 Kathleen.A.Ryan@hitchcock.org
Principal Investigator: Lloyd Kasper, M.D.
United States, New Jersey
UMDNJ-Robert Wood Johnson Medical Center	Recruiting
New Brunswick, New Jersey, United States, 08901
Contact: Yaritza Rosario 732-235-7099 rosariym@umdnj.edu
Principal Investigator: Suhayl Dhib-Jalbut, M.D.
United States, New Mexico
University of New Mexico	Recruiting
Albuquerque, New Mexico, United States, 87131
Contact: Molly Harmon, MS 505-272-6988 MoHarmon@salud.unm.edu
Principal Investigator: Corey Ford, M.D.
United States, New York
Columbia University	Recruiting
New York City, New York, United States, 10032
Contact: Yanette Franklin, RN 212-305-1209 yfranklin@neuro.columbia.edu
Contact: Shahram Khalid, RN (212) 305-1209 skhalid@neuro.columbia.edu
Principal Investigator: Mark Tullman, M.D.
United States, Ohio
Ohio State University	Recruiting
Columbus, Ohio, United States, 43221
Contact: Lisa Hafer, RN 614-293-7877 lisa.hafer@osumc.edu
Contact: Cindy Overholts, RN (614)293-7877 Cindy.Overholts@osumc.edu
Principal Investigator: Deborah J. Lynn, M.D.
United States, Pennsylvania
University of Pennsylvania	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Vanessa Zimmerman, RN 215-349-5162 Vanessa.Zimmerman@uphs.upenn.edu
Principal Investigator: Dina Jacobs, M.D.
United States, Texas
University of Texas Southwestern	Recruiting
Dallas, Texas, United States, 75390-8575
Contact: Gina Remington, RN 214-645-0560 Gina.Remington@UTSouthwestern.edu
Contact: Diane Veath, LVN (214)645-0544 diane.veath@UTSouthwestern.edu
Principal Investigator: Elliot Frohman, M.D.
United States, Utah
Western Institute for Biomedical Research	Recruiting
Salt Lake City, Utah, United States, 84158
Contact: Julia Klein 801-582-1565 ext 2014 Julia.klein@va.gov
Contact: Julia Klein (801)232-2109
Principal Investigator: John Rose, M.D.

Sponsors and Collaborators

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, Baltimore, Maryland

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.

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:	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

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:	University of California, Los Angeles ( Rhonda Voskuhl, M.D. )
Study ID Numbers:	RO1-NS051591, NIH grant RO1-NS051591, NMSS grant RG 3915
Study First Received:	March 22, 2007
Last Updated:	May 4, 2009
ClinicalTrials.gov Identifier:	NCT00451204 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of California, Los Angeles:

Multiple sclerosis
estrogen
estriol
progesterone

Study placed in the following topic categories:

Estrogens
Autoimmune Diseases
Demyelinating Diseases
Progesterone
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Sclerosis

Multiple Sclerosis, Relapsing-Remitting
Hormones
Copolymer 1
Multiple Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System

Additional relevant MeSH terms:

Estrogens
Autoimmune Diseases
Demyelinating Diseases
Immune System Diseases
Physiological Effects of Drugs
Nervous System Diseases
Hormones, Hormone Substitutes, and Hormone Antagonists
Sclerosis

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

ClinicalTrials.gov processed this record on July 02, 2009