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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Combination Trial of Copaxone Plus Estriol in RRMS

Conditions
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Relapsing Remitting Multiple Sclerosis

Intervention / Treatment
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* Drug: Estriol
* Drug: Placebo
* Drug: Copaxone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Estriol plus Copaxone injections QD<br>Estriol Capsules (daily) plus Copaxone injections (daily). Progestin capsules given for 2 weeks every 3 months to avoid unopposed estrogens. | Drug: Estriol<br>* Estriol 8 mg capsule, once per day, duration of treatment is 2 years<br>* Other names: estrogen;Drug: Copaxone<br>* Injection, once a day, all subjects<br>* Other names: glatiramer acetate;|
| Placebo Comparator: Placebo plus Copaxone injections QD<br>Placebo Capsules (daily) plus Copaxone injections (daily). A second placebo capsule given for 2 weeks every 3 months. | Drug: Placebo<br>* Placebo capsule, once a day, treatment duration is 2 years<br>* Other names: sugar pill;Drug: Copaxone<br>* Injection, once a day, all subjects<br>* Other names: glatiramer acetate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse Event, Annualized Relapse Rate | Met all criteria for relapse except not confirmed to have increase in EDSS by an independent examiner. | 24 months | 
| Confirmed Relapse, Probability of First Relapse |  | 24 months | 
| Relapse Event, Probability of First Relapse Event |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple sclerosis, estrogen, estriol, progesterone