Trial record 1 of 2 for: estriol AND multiple sclerosis

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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

Tracking Information

First Received Date ^ICMJE

March 22, 2007

Last Updated Date

May 10, 2016

Start Date ^ICMJE

March 2007

Primary Completion Date

July 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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

A confirmed relapse was defined as new neurological symptoms or worsening of pre-existing symptoms, lasting at least 48 hours in a subject who had been neurologically stable or improving in the previous 30 days, accompanied by objective change in the neurological examination (worsening of 0.5 points on the EDSS or worsening by 1.0 or more points on the pyramidal, cerebellar, brainstem or visual functional system scores), not due to fatigue alone and not associated with fever or infection.

Original Primary Outcome Measures ^ICMJE

Relapse Rate

Change History

Complete list of historical versions of study NCT00451204 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

Relapse Event, Annualized Relapse Rate [ Time Frame: 24 months ]
Met all criteria for relapse except not confirmed to have increase in EDSS by an independent examiner.
Confirmed Relapse, Probability of First Relapse [ Time Frame: 24 months ]
Relapse Event, Probability of First Relapse Event [ Time Frame: 24 months ]

Original Secondary Outcome Measures ^ICMJE

Relapse Related Secondary
"Relapse Event" Rate
time to first "Relapse"
time to first "Relapse Event"
proportion of subjects "Relapse" free at each year
proportion of subjects "Relapse Event" free at each year
number of "Relapses" per subject
number of "Relapse Events" per subject
severity of "Relapse" as assessed by degree of worsening of EDSS
severity of "Relapse Event" as assessed by degree of worsening of EDSS
severity of "Relapse" as assessed by degree of worsening of MSFC.
severity of "Relapse Event" as assessed by degree of worsening of MSFC.
number of times IV solumedrol was administered per subject for treatment of "Relapses."
number of times IV solumedrol was administered per subject for treatment of "Relapse Events."
Disability Related Secondary
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
EDSS progression from baseline at conclusion
MSFC progression from baseline at conclusion
Improvement in PASAT scores between baseline and conclusion
Improvement in 7-24 Spatial Recall test scores between baseline and conclusion
Improvement in Selective Reminding Test scores between baseline and conclusion

Current Other Outcome Measures ^ICMJE

Confirmed Relapse, Annualized Relapse Rate [ Time Frame: 12 months ]
A confirmed relapse was defined as new neurological symptoms or worsening of pre-existing symptoms, lasting at least 48 hours in a subject who had been neurologically stable or improving in the previous 30 days, accompanied by objective change in the neurological examination (worsening of 0.5 points on the EDSS or worsening by 1.0 or more points on the pyramidal, cerebellar, brainstem or visual functional system scores), not due to fatigue alone and not associated with fever or infection.
Relapse Event, Annualized Relapse Rate [ Time Frame: 12 months ]
Met all criteria for relapse except not confirmed to have increase in EDSS by an independent examiner.

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

A Combination Trial of Copaxone Plus Estriol in RRMS

Brief Summary

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

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.

Study Type ^ICMJE

Interventional

Study Phase

Phase 2

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment

Condition ^ICMJE

Relapsing Remitting Multiple Sclerosis

Intervention ^ICMJE

Drug: Estriol
Estriol 8 mg capsule, once per day, duration of treatment is 2 years
Other Names:
- E3
- estrogen
Drug: Placebo
Placebo capsule, once a day, treatment duration is 2 years

Other Name: "sugar pill"
Drug: Copaxone
Injection, once a day, all subjects

Other Name: glatiramer acetate

Study Arms

Active Comparator: 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.
Interventions:
- Drug: Estriol
- Drug: Copaxone
Placebo Comparator: Placebo plus Copaxone injections QD
Placebo Capsules (daily) plus Copaxone injections (daily). A second placebo capsule given for 2 weeks every 3 months.
Interventions:
- Drug: Placebo
- Drug: Copaxone

Publications *

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Completed

Enrollment ^ICMJE

158

Completion Date

July 2014

Primary Completion Date

July 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Sex/Gender

Sexes Eligible for Study:

Female

Ages

18 Years to 50 Years (Adult)

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

Canada, United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT00451204

Other Study ID Numbers ^ICMJE

R01NS051591( U.S. NIH Grant/Contract )
R01NS051591 ( U.S. NIH Grant/Contract )
RG3915 ( Other Grant/Funding Number: NMSS )

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Not Provided

IPD Sharing Statement

Plan to Share IPD:	Yes
Plan Description:	Investigators interested in further research using the data should contact Dr. Voskuhl with proposed plans and request.

Responsible Party

Rhonda Voskuhl, University of California, Los Angeles

Study Sponsor ^ICMJE

University of California, Los Angeles

Collaborators ^ICMJE

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)

Investigators ^ICMJE

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:	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, MN
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:	Lloyd Kasper, M.D.	Dartmouth University, Lebanon, NH

PRS Account

University of California, Los Angeles

Verification Date

May 2016

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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