POPART'MUS: Prevention of Post Partum Relapses With Progestin and Estradiol in Multiple Sclerosis

Study Overview
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Brief Summary
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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-thirds in the rate of relapses during the third trimester of pregnancy and a significant increase by two-thirds 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 the 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 the anti-inflammatory responses of the Th2 type. They may also play a direct role in the 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 administering high doses of progestin (nomegestrol acetate), 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.

Official Title
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POPART'MUS: Prevention of Post Partum Relapses With Progestin and Estradiol in Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: nomegestrol acetate
* Drug: estradiol
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: MS according to MacDonald 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 criteria for MS Primary progressive MS Possible MS or no MS according to MacDonald criteria Ongoing or previous myocardial infarction, stroke or venous thromboembolism Ongoing or previous breast cancer, or cancer of the uterus Severe liver disorder Undiagnosed genital bleeding Hypersensitivity to one of the study treatments Desire for lactation Desire for an MS disease-modifying treatment in the 24 weeks after delivery Women participating in another trial with a drug Refusal of non-hormonal contraception in the 12 weeks following delivery Consent form not signed

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 |
| --- | --- |
| Experimental: NOMA + estradiol<br>Oral NOMA (LUTENYL® 10 mg/day) combined with transdermal Estradiol (DERMESTRIL SEPTEM® 75 mcg, once a week), | Drug: nomegestrol acetate<br>* 10 mg/day<br>Drug: estradiol<br>* 75 mcg, once a week<br>|
| Placebo Comparator: placebo<br>Matching placebo treatments | Drug: placebo<br>* matching placebo treatments<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the rate of relapses during the first 12 weeks after delivery, between the treated and placebo groups |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients who remain relapse-free during the 12-week period after delivery |  | 12 weeks | 
| Rate of relapses, percentage of patients who remain relapse-free during the 24-week period after delivery |  | 24 weeks | 
| Rate of relapses, percentage of patients who remain relapse-free during the 12- to 24-week period after delivery |  | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple sclerosis. Relapses. Post partum. Pregnancy. Delivery. Hormones. Progesterone. Estradiol. Clinical trial. Prevention.