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

Sponsor

Hospices Civils de Lyon (Other)

Overall Status

Unknown status

CT.gov ID

NCT00127075

Collaborator

(none)

300

Enrollment

Location

Arms

Duration (Months)

3.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: nomegestrol acetate Drug: estradiol Drug: placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 1, 2005

Anticipated Primary Completion Date :

Apr 1, 2012

Anticipated Study Completion Date :

Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NOMA + estradiol Oral NOMA (LUTENYL® 10 mg/day) combined with transdermal Estradiol (DERMESTRIL SEPTEM® 75 mcg, once a week),	Drug: nomegestrol acetate 10 mg/day Drug: estradiol 75 mcg, once a week
Placebo Comparator: placebo Matching placebo treatments	Drug: placebo matching placebo treatments

Arm

Intervention/Treatment

Experimental: NOMA + estradiol

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

Drug: nomegestrol acetate

10 mg/day

Drug: estradiol

75 mcg, once a week

Placebo Comparator: placebo

Matching placebo treatments

Drug: placebo

matching placebo treatments

Outcome Measures

Primary Outcome Measures

To compare the rate of relapses during the first 12 weeks after delivery, between the treated and placebo groups [12 weeks]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

Female

Accepts 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