A Combination Trial of Copaxone Plus Estriol in RRMS - Full Text View

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

MedlinePlus related topics:

Dietary Sodium Multiple Sclerosis

ChemIDplus related topics:

Estriol 16-Epiestriol Progesterone Copolymer 1

U.S. FDA Resources

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

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 2011
Estimated Primary Completion Date:	April 2011 (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: Sofia Quesada	(310)825-7313	squezada@mednet.ucla.edu

Contact: Mike Montag	(310)825-7313	MMontag@mednet.ucla.edu

Locations


United States, California
	University of California, Los Angeles	Recruiting
	Los Angeles, California, United States, 90095
	Contact: Sofia Quesada 310-825-7313 squezada@mednet.ucla.edu
	Contact: Mike Montag (310)825-7313 MMontag@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, 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, Missouri
	Washington University	Recruiting
	Saint Louis, Missouri, United States, 63110
	Contact: Terri Radake, R.N. 314-747-1761 Radaket@msnotes.com
	Contact: Monica Fairburn (314)747-5576
	Principal Investigator: Anne Cross, 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, Ohio
	Ohio State University	Recruiting
	Columbus, Ohio, United States, 43221
	Contact: Lisa Hafer 614-293-7877 Lisa.hafer@osumc.edu
	Principal Investigator: Deborah J. Lynn, M.D.

United States, Texas
	University of Texas Southwestern	Recruiting
	Dallas, Texas, United States, 75390-8575
	Contact: Gina Remington 214-645-0560 Gina.Remington@UTSouthwestern.edu
	Contact: Gina Remington (214)786-0275
	Principal Investigator: Elliot Frohman, M.D.

United States, Utah
	Salt Lake Cuty VA Medical Center	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

Washington University School of Medicine, Saint Louis, MO

University of Texas Southwestern Medical Center

Ohio State University

University of Medicine and Dentistry New Jersey

University of Chicago

Salt Lake City VA Medical Center, Salt Lake City, UT

National Multiple Sclerosis Society

National Institutes of Health (NIH)

Pipex 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:	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.	Salt Lake City VA Medical Center, Salt Lake City, UT

Principal Investigator:	Barbara Giesser, M.D.	University of California, Los Angeles (UCLA), Los Angeles, CA

More 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
First Received:	March 22, 2007
Last Updated:	March 27, 2008
ClinicalTrials.gov Identifier:	NCT00451204
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:

Copolymer 1

Autoimmune Diseases

Multiple Sclerosis

Progesterone

Demyelinating Diseases

Demyelinating Autoimmune Diseases, CNS

Demyelinating diseases

Sclerosis

Multiple Sclerosis, Relapsing-Remitting

Autoimmune Diseases of the Nervous System

Additional relevant MeSH terms:

Pathologic Processes

Immune System Diseases

Nervous System Diseases

ClinicalTrials.gov processed this record on October 07, 2008

Sponsors and Collaborators:	University of California, Los Angeles Washington University School of Medicine, Saint Louis, MO University of Texas Southwestern Medical Center Ohio State University University of Medicine and Dentistry New Jersey University of Chicago Salt Lake City VA Medical Center, Salt Lake City, UT National Multiple Sclerosis Society National Institutes of Health (NIH) Pipex Pharmaceuticals, Ann Arnor, MI
Information provided by:	University of California, Los Angeles
ClinicalTrials.gov Identifier:	NCT00451204