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.

Condition	Intervention	Phase
Multiple Sclerosis	Drug: estroprogestins  Drug: interferon-beta 1a	Phase II

Further Study Details: 

Primary Outcomes: Safety assessment at 6, 12, 18 and 24 months, including adverse events, physical examination and laboratory parameters; Relapse rate at 6, 12, 18 and 24 months,; EDSS progression at 12 and 24 months,; MS functional composite score at 12 and 24 months,
Secondary Outcomes: Number and volume of new gad-enhancing lesions at 12 and 24 months; Number of new T1 and T2 lesions at 12 and 24 months; Brain volume changes at 12 and 24 months; Neuropsychological examination at 0, 12, 24 months; Hamilton scale for depression score at 0, 12, 24 months; MS Quality of Life scale score(MSQOL54)at 0, 12, 24 months; Fatigue Severity Scale score at 0, 12, 24 months
Expected Total Enrollment:  200

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.

Ages Eligible for Study:  18 Years   -   40 Years,  Genders Eligible for Study:  Female

Criteria

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

Please refer to this study by ClinicalTrials.gov identifier  NCT00151801

Carlo Pozzilli, MD      +39-06-49914716    carlo.pozzilli@uniroma1.it
Fabiana Marinelli, MD      +39-338-2955443    fabiana.marinelli@uniroma1.it

Italy
      Department of Neurology - University of Rome La Sapienza, Rome,  00100,  Italy; Recruiting

Study chairs or principal investigators

Valentina Tomassini, MD,  Study Chair,  Department of Neurological Science University of Rome "La Sapienza"   
Fabiana Marinelli, MD,  Principal Investigator,  Department of Neurological Science, University of Rome "La Sapienza"   
Carlo Pozzilli, MD,  Study Director,  Department of Neurological Science, University of Rome "La Sapienza"   

Study ID Numbers:  NEU - PIL - 03
Last Updated:  September 8, 2005
Record first received:  September 8, 2005
ClinicalTrials.gov Identifier:  NCT00151801
Health Authority: Italy: Ministry of Health
ClinicalTrials.gov processed this record on 2005-09-13