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

NCT00451204 | Completed Phase 2 Results DMC

• 2 other identifiers: R01NS051591RG3915
• Study Type: interventional
• Target: 158
• Locations: 2 countries
• Sites: 16

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.

Conditions

Relapsing Remitting Multiple Sclerosis

Keywords

Multiple sclerosis; estrogen; estriol; progesterone

Outcome Measures

Primary Outcomes (1)

• Confirmed Relapse, Annualized Relapse Rate

  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.

  24 months

Secondary Outcomes (3)

• Relapse Event, Annualized Relapse Rate

  24 months

• Confirmed Relapse, Probability of First Relapse

  24 months

• Relapse Event, Probability of First Relapse Event

  24 months

Other Outcomes (2)

• Confirmed Relapse, Annualized Relapse Rate

  12 months

• Relapse Event, Annualized Relapse Rate

  12 months

Study Arms (2)

Estriol plus Copaxone injections QD

ACTIVE COMPARATOR

Estriol Capsules (daily) plus Copaxone injections (daily). Progestin capsules given for 2 weeks every 3 months to avoid unopposed estrogens.

Drug: Estriol; Drug: Copaxone

Placebo plus Copaxone injections QD

PLACEBO COMPARATOR

Placebo Capsules (daily) plus Copaxone injections (daily). A second placebo capsule given for 2 weeks every 3 months.

Drug: Placebo; Drug: Copaxone

Interventions

Estriol DRUG

Estriol 8 mg capsule, once per day, duration of treatment is 2 years

Also known as: E3, estrogen

Estriol plus Copaxone injections QD

Placebo DRUG

Placebo capsule, once a day, treatment duration is 2 years

Also known as: "sugar pill"

Placebo plus Copaxone injections QD

Copaxone DRUG

Injection, once a day, all subjects

Also known as: glatiramer acetate

Estriol plus Copaxone injections QD; Placebo plus Copaxone injections QD

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of relapsing remitting multiple sclerosis
• At least one relapse in the last two years

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Los Angeles: lead
• Washington University School of Medicine: collaborator
• University of Texas Southwestern Medical Center: collaborator
• Ohio State University: collaborator
• University of Medicine and Dentistry of New Jersey: collaborator
• University of Chicago: collaborator
• University of Utah: collaborator
• Johns Hopkins University: collaborator
• University of Kansas Medical Center: collaborator
• University of Minnesota: collaborator
• Mayo Clinic: collaborator
• University of Colorado, Denver: collaborator
• University of New Mexico: collaborator
• University of Pennsylvania: collaborator
• Dartmouth-Hitchcock Medical Center: collaborator
• National Multiple Sclerosis Society: collaborator
• National Institutes of Health (NIH): collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (16)

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Kansas

Kansas City, Kansas, 66160, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287-6965, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Dartmouth Medical School

Lebanon, New Hampshire, 03765, United States

Location

UMDNJ-Robert Wood Johnson Medical Center

New Brunswick, New Jersey, 08901, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

Ohio State University

Columbus, Ohio, 43221, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390-8575, United States

Location

Western Institute for Biomedical Research

Salt Lake City, Utah, 84158, United States

Location

Montreal Neurological Institute

Montreal, Canada

Location

Related Publications (9)

• 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. doi: 10.1002/ana.10301.

  PMID: 12325070 BACKGROUND

• 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. doi: 10.4049/jimmunol.171.11.6267.

  PMID: 14634144 BACKGROUND

• 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. doi: 10.1523/JNEUROSCI.0453-06.2006.

  PMID: 16793889 BACKGROUND

• 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. doi: 10.1073/pnas.0703783104. Epub 2007 Sep 4.

  PMID: 17785421 BACKGROUND

• 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. doi: 10.1001/archneur.64.5.683.

  PMID: 17502467 BACKGROUND

• 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.

  PMID: 19668239 BACKGROUND

• 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.

  PMID: 22525427 BACKGROUND

• 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.

  PMID: 21555578 BACKGROUND

• 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.

  PMID: 26621682 RESULT

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Interventions

Estriol; Estrogens; Sugars; Glatiramer Acetate

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr. Rhonda Voskuhl
• Organization: University of California Los Angeles

rvoskuhl@mednet.ucla.edu

310-206-4636

Study Officials

• Rhonda Voskuhl, M.D.

  University of California, Los Angeles (UCLA), Los Angeles, CA

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

• Dean Wingerchuk, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• John Corboy, M.D.

  University of Colorado, Denver

  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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Neurology; Director Multiple Sclerosis Program

Study Record Dates

• First Submitted: March 22, 2007
• First Posted: March 23, 2007
• Study Start: March 1, 2007
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: June 16, 2016
• Results First Posted: June 16, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will share

Locations

CA (1); US (15)