Multiple sclerosis (MS) affects 1 in 1000 people in western countries, mainly women in their childbearing years. It is an autoimmune disease of the central nervous system (CNS), which results in a chronic focal inflammatory response with subsequent demyelination and axonal loss. Recent prospective studies reported a significant decline by two-third in the rate of relapses during the third trimester of pregnancy and a significant increase by two-third during the first three months post-partum by comparison to the relapse rate observed during the year prior to the pregnancy (Confavreux et al., 1998). These dramatic changes in the relapse rate occur at a time when impregnation of many substances, among which sexual steroids, is at its highest, before a dramatic decline to the pre-pregnancy levels, immediately following delivery.

It may be hypothesized that sexual steroids could exert beneficial effects through a modulation of the immune state with a lowering of the pro-inflammatory lymphocyte responses of the Th1 type and an enhancement of anti-inflammatory responses of the Th2 type. They may also play a direct role in remyelination of central nervous system lesions, as they do in the peripheral nervous system. The POPART’MUS study is a European, multicentre, randomized, placebo-controlled and double-blind clinical trial, which aims to prevent MS relapses related to the post-partum condition, by administrating high doses of progestin, in combination with endometrial protective doses of estradiol. Treatment will be given immediately after delivery and continuously during the first three months post-partum. Assuming the results of the trial to be positive, this new treatment could be considered in the relapsing-remitting phase of the disease in women afar from pregnancy and post-partum.

Condition	Intervention	Phase
Multiple Sclerosis	Drug: nomegestrol acetate  Drug: estradiol	Phase III

Further Study Details: 

Primary Outcomes: To compare the rate of relapses during the first 12 weeks after delivery, between the treated and placebo groups.
Secondary Outcomes: Percentage of patients who remain relapse-free during the 12-week period after delivery; Rate of relapses, percentage of patients who remain relapse-free during the 24-week period after delivery; Rate of relapses, percentage of patients who remain relapse-free during the 12- to 24-week period after delivery
Expected Total Enrollment:  300

Ages Eligible for Study:  18 Years   -   50 Years,  Genders Eligible for Study:  Female

Criteria

Inclusion Criteria:

• MS according to Mac Donald criteria (including clinically isolated syndromes fulfilling magnetic resonance imaging [MRI] criteria for MS diagnosis)
• Relapsing-remitting or secondary progressive MS
• Expanded disability status scale (EDSS) ≤ 6.0
• Pregnancy ≤ 36 weeks of amenorrhea

Exclusion Criteria:

• Age < 18 years
• Clinical isolated syndrome not fulfilling MacDonald’s criteria for MS
• Primary progressive MS
• Possible MS or no MS according to Mc Donald''''s criteria,
• Ongoing or previous myocardial infarction, stroke or venous thrombo-embolism
• Ongoing or previous breast cancer, or cancer of the uterus
• Severe liver disorder
• Undiagnosed genital bleeding
• Hypersensitivity to one of the study treatment
• Desire for lactation
• Desire for a MS disease-modifying treatment in the 24 weeks after delivery
• Woman participating to another trial with a drug
• Refusal of non-hormonal contraception in the 12 weeks following delivery
• Consent form not signed

Please refer to this study by ClinicalTrials.gov identifier  NCT00127075

France
      Achiti, Lyon,  69677,  France; Recruiting

Study chairs or principal investigators

Christian Confavreux, MD,  Principal Investigator,  Hospices Civils de Lyon   

Study ID Numbers:  2004-363
Last Updated:  August 19, 2005
Record first received:  August 4, 2005
ClinicalTrials.gov Identifier:  NCT00127075
Health Authority: France: Afssaps - French Health Products Safety Agency
ClinicalTrials.gov processed this record on 2005-08-23