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

NCT ID: NCT00127075

Last Updated: 2011-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

300 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-06-30

Study Completion Date

2012-04-30

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.

Detailed Description

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Conditions

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Multiple Sclerosis

Keywords

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Multiple sclerosis. Relapses. Post partum. Pregnancy. Delivery. Hormones. Progesterone. Estradiol. Clinical trial. Prevention.

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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NOMA + estradiol

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

Group Type EXPERIMENTAL

nomegestrol acetate

Intervention Type DRUG

10 mg/day

estradiol

Intervention Type DRUG

75 mcg, once a week

placebo

Matching placebo treatments

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

matching placebo treatments

Interventions

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nomegestrol acetate

10 mg/day

Intervention Type DRUG

estradiol

75 mcg, once a week

Intervention Type DRUG

placebo

matching placebo treatments

Intervention Type DRUG

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Hospices Civils de Lyon

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christian Confavreux, MD

Role: PRINCIPAL_INVESTIGATOR

Hospices Civils de Lyon

Locations

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Hôpital Pierre Wertheimer

Bron, , France

Site Status

Countries

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France

References

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Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T. Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group. N Engl J Med. 1998 Jul 30;339(5):285-91. doi: 10.1056/NEJM199807303390501.

Reference Type BACKGROUND
PMID: 9682040 (View on PubMed)

Confavreux C, Hutchinson M, Hours M, Cortinovis-Tourniaire P, Grimaud J, Moreau T. [Multiple sclerosis and pregnancy: clinical issues]. Rev Neurol (Paris). 1999 Mar;155(3):186-91. French.

Reference Type BACKGROUND
PMID: 10339787 (View on PubMed)

Vukusic S, Hutchinson M, Hours M, Moreau T, Cortinovis-Tourniaire P, Adeleine P, Confavreux C; Pregnancy In Multiple Sclerosis Group. Pregnancy and multiple sclerosis (the PRIMS study): clinical predictors of post-partum relapse. Brain. 2004 Jun;127(Pt 6):1353-60. doi: 10.1093/brain/awh152. Epub 2004 May 6.

Reference Type BACKGROUND
PMID: 15130950 (View on PubMed)

Vukusic S, Ionescu I, El-Etr M, Schumacher M, Baulieu EE, Cornu C, Confavreux C; Prevention of Post-Partum Relapses with Progestin and Estradiol in Multiple Sclerosis Study Group. The Prevention of Post-Partum Relapses with Progestin and Estradiol in Multiple Sclerosis (POPART'MUS) trial: rationale, objectives and state of advancement. J Neurol Sci. 2009 Nov 15;286(1-2):114-8. doi: 10.1016/j.jns.2009.08.056. Epub 2009 Sep 15.

Reference Type DERIVED
PMID: 19758607 (View on PubMed)

Related Links

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http://www.edmus.org

European database for multiple sclerosis

Other Identifiers

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2004.363

Identifier Type: -

Identifier Source: org_study_id