Safety and Tolerability of Interferon-Beta-1a and Estroprogestins Association in MS Patients

Safety and Tolerability of Oral Two-Doses Estroprogestins Associated With Interferon-Beta 1a in Patients With Relapsing-Remitting Multiple Sclerosis

Clinical and experimental evidences suggests an immunomodulatory effect of sex hormones in multiple sclerosis.

The role of oral estroprogestins in the pathogenesis and in the clinical course of the disease is actually unknown.

The aim of the study is to investigate safety and tolerability of association of estroprogestins in two different doses with interferon-beta 1a in patients with relapsing-remitting multiple sclerosis.

Phase 2, randomised, single blind, three arms study.

Follow-up of 24 months.

The study will include relapsing-remitting multiple sclerosis female patients.

Patients will be equally randomised into three groups: 1) patients treated with IFN-beta 1a (44 mcg for three times a week), 2) patients treated with IFN-beta 1a and lower-dose estroprogestins (desogestrel 150 mcg, etinilestradiol 20 mcg), 3) patients treated with IFN-beta 1a and higher-dose estroprogestins (desogestrel 25 mcg, etinilestradiol 40 mcg).

Safety and tolerability of the treatment will be evaluated using neurological examination and MRI analysis.

A complete neurological examination (with EDSS) will be performed at month 0, 6, 12, 18 and 24.

MRI examination will be assessed at baseline and at month 12 and 24. In the same day of MRI examination we'll collect blood samples for hormonal analysis (we'll measure sex hormones in the follicular and in the luteal phase of a single menstrual cycle).

During the follow-up patients will be evaluated also with: MS-Functional Composite at month 0, 6, 12, 18, 24; neuropsychological evaluation at month 0, 12, 24; Fatigue Severity Scale at month 0, 12, 24; Hamilton Depression Scale at month 0, 12, 24; Quality of Life scale (MSQOL54) at month 0, 12, 24.

Inclusion Criteria:

• Female patients
• Clinically definite relapsing-remitting MS according to the McDonald criteria
• Age between 18-40 y.o.
• EDSS from 0 to 4.0, inclusive

Exclusion Criteria:

• History of migraine or thromboembolic events
• Reproductive system disorders
• Pregnancy or suspension of pregnancy within 12 months prior to randomisation
• Prior use of estroprogestins within the last 3 months prior to randomisation
• Prior use of immunosuppressive drugs within the last 12 months prior to randomisation
• Prior use of immunomodulating drugs within the last 6 months prior to randomisation
• Prior use of corticosteroids within the last 3 months prior to randomisation
• Have clinical relapse 30 days prior to randomisation