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

This study has been completed.

Sponsor:

Collaborators:

Washington University School of Medicine

University of Texas Southwestern Medical Center

Ohio State University

University of Medicine and Dentistry of New Jersey

University of Chicago

University of Utah

Johns Hopkins University

University of Kansas Medical Center

University of Minnesota, MN

Mayo Clinic

University of Colorado, Aurora

University of New Mexico

University of Pennsylvania

Dartmouth-Hitchcock Medical Center

National Multiple Sclerosis Society

National Institutes of Health (NIH)

National Institute of Neurological Disorders and Stroke (NINDS)

Information provided by (Responsible Party):

Rhonda Voskuhl, University of California, Los Angeles

ClinicalTrials.gov Identifier:

NCT00451204

First received: March 22, 2007

Last updated: May 10, 2016

Last verified: May 2016

History of Changes

Results First Received: January 20, 2016

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double Blind (Participant, Care Provider, Investigator); Primary Purpose: Treatment
Condition:	Relapsing Remitting Multiple Sclerosis
Interventions:	Drug: Estriol Drug: Placebo Drug: Copaxone

Participant Flow

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Recruitment Details

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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Estriol Capsules Plus Copaxone Injections	Estriol: Estriol 8 mg capsule, once per day, duration of treatment is 2 years
Placebo Capsules Plus Copaxone Injections	Placebo: Placebo capsule, once per day, treatment duration is 2 years

Participant Flow: Overall Study

	Estriol Capsules Plus Copaxone Injections	Placebo Capsules Plus Copaxone Injections
STARTED	82	76
COMPLETED	60 ^[1]	56
NOT COMPLETED	22	20
Adverse Event	4	6
Lack of Efficacy	4	4
Lost to Follow-up	4	4
Protocol Violation	1	0
Patient refusal	8	4
Other	1	2

^[1]	60 completed the study but 3 stopped study drug(s) early

Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Relapsing remitting multiple sclerosis women aged 18 to 50 years.

Reporting Groups

	Description
Estriol Capsules Plus Copaxone Injections	Estriol: Estriol 8 mg capsule, once per day, duration of treatment is 2 years
Placebo Capsules Plus Copaxone Injections	Placebo: Placebo capsule, once a day, treatment duration is 2 years
Total	Total of all reporting groups

Baseline Measures

	Estriol Capsules Plus Copaxone Injections	Placebo Capsules Plus Copaxone Injections	Total
Overall Participants Analyzed [Units: Participants]	82	76	158

Age [Units: Participants]
<=18 years	0	0	0
Between 18 and 65 years	82	76	158
>=65 years	0	0	0

Age [Units: Years] Mean (Standard Deviation)	37.7 (7.6)	37.1 (7.3)	37.4 (7.45)

Gender [Units: Participants]
Female	82	76	158
Male	0	0	0

Region of Enrollment [Units: Participants]
United States	82	76	158

Outcome Measures

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1. Primary:

Confirmed Relapse, Annualized Relapse Rate [ Time Frame: 24 months ]

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2. Secondary:

Relapse Event, Annualized Relapse Rate [ Time Frame: 24 months ]

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3. Secondary:

Confirmed Relapse, Probability of First Relapse [ Time Frame: 24 months ]

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4. Secondary:

Relapse Event, Probability of First Relapse Event [ Time Frame: 24 months ]

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5. Other Pre-specified:

Confirmed Relapse, Annualized Relapse Rate [ Time Frame: 12 months ]

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6. Other Pre-specified:

Relapse Event, Annualized Relapse Rate [ Time Frame: 12 months ]

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Serious Adverse Events

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Other Adverse Events

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Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact:

Name/Title: Dr. Rhonda Voskuhl
Organization: University of California Los Angeles
phone: 310-206-4636
e-mail: rvoskuhl@mednet.ucla.edu

Publications of Results:

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.

Other 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.

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.

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.

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.

Responsible Party:	Rhonda Voskuhl, University of California, Los Angeles
ClinicalTrials.gov Identifier:	NCT00451204 History of Changes
Other Study ID Numbers:	R01NS051591 ( US NIH Grant/Contract Award Number ) RG3915 ( Other Grant/Funding Number: NMSS )
Study First Received:	March 22, 2007
Results First Received:	January 20, 2016
Last Updated:	May 10, 2016

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