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

Phase 3
Conditions
Multiple Sclerosis
Interventions
Registration Number
NCT00127075
Lead Sponsor
Hospices Civils de Lyon
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
Female
Target Recruitment
300
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
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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
placeboplaceboMatching placebo treatments
NOMA + estradiolestradiolOral NOMA (LUTENYL® 10 mg/day) combined with transdermal Estradiol (DERMESTRIL SEPTEM® 75 mcg, once a week),
NOMA + estradiolnomegestrol acetateOral NOMA (LUTENYL® 10 mg/day) combined with transdermal Estradiol (DERMESTRIL SEPTEM® 75 mcg, once a week),
Primary Outcome Measures
NameTimeMethod
To compare the rate of relapses during the first 12 weeks after delivery, between the treated and placebo groups12 weeks
Secondary Outcome Measures
NameTimeMethod
Percentage of patients who remain relapse-free during the 12-week period after delivery12 weeks
Rate of relapses, percentage of patients who remain relapse-free during the 24-week period after delivery24 weeks
Rate of relapses, percentage of patients who remain relapse-free during the 12- to 24-week period after delivery24 weeks

Trial Locations

Locations (1)

Hôpital Pierre Wertheimer

🇫🇷

Bron, France

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