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