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

University of California, Los Angeles (UCLA)

Status and phase: Completed; Phase 2

Conditions: Relapsing Remitting Multiple Sclerosis

Treatments: Drug: Estriol; Drug: Copaxone; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00451204

RG3915 (Other Grant/Funding Number)

R01NS051591 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 158 patients

Sex: Female

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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158 participants in 2 patient groups, including a placebo group

Estriol plus Copaxone injections QD

Active Comparator group

Description:

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

Treatment:

Drug: Copaxone

Drug: Estriol

Placebo plus Copaxone injections QD

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Drug: Copaxone