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

Civil Hospices of Lyon

Status and phase: Unknown; Phase 3

Conditions: Multiple Sclerosis

Treatments: Drug: placebo; Drug: nomegestrol acetate; Drug: estradiol

Study type: Interventional

Funder types: Other

Identifiers

NCT00127075

2004.363

Details and patient eligibility

About

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.

Enrollment: 300 estimated patients

Sex: Female

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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300 participants in 2 patient groups, including a placebo group

NOMA + estradiol

Experimental group

Description:

Oral NOMA (LUTENYL® 10 mg/day) combined with transdermal Estradiol (DERMESTRIL SEPTEM® 75 mcg, once a week),

Treatment:

Drug: estradiol

Drug: nomegestrol acetate

placebo

Placebo Comparator group

Description:

Matching placebo treatments

Treatment:

Drug: placebo