NCT00127075

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
300

participants targeted

Target at P50-P75 for phase_3 multiple-sclerosis

Timeline
Completed

Started Jun 2005

Longer than P75 for phase_3 multiple-sclerosis

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2005

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

August 4, 2005

Completed
1 day until next milestone

First Posted

Study publicly available on registry

August 5, 2005

Completed
6.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2012

Completed
Last Updated

December 30, 2011

Status Verified

December 1, 2011

Enrollment Period

6.8 years

First QC Date

August 4, 2005

Last Update Submit

December 28, 2011

Conditions

Multiple Sclerosis

Keywords

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

Outcome Measures

Primary Outcomes (1)

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

    12 weeks

Secondary Outcomes (3)

  • 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

Study Arms (2)

NOMA + estradiol

EXPERIMENTAL

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

Drug: nomegestrol acetateDrug: estradiol

placebo

PLACEBO COMPARATOR

Matching placebo treatments

Drug: placebo

Interventions

nomegestrol acetateDRUG

10 mg/day

NOMA + estradiol
estradiolDRUG

75 mcg, once a week

NOMA + estradiol
placeboDRUG

matching placebo treatments

placebo

Eligibility Criteria

Age18 Years - 50 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hôpital Pierre Wertheimer

Bron, 69677, France

Location

Related Publications (4)

  • 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.

    PMID: 9682040BACKGROUND

  • 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.

    PMID: 10339787BACKGROUND

  • 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.

    PMID: 15130950BACKGROUND

  • 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.

    PMID: 19758607DERIVED

Related Links

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

nomegestrol acetateEstradiol

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemNervous System DiseasesDemyelinating DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

EstrenesEstranesSteroidsFused-Ring CompoundsPolycyclic CompoundsEstradiol CongenersGonadal Steroid HormonesGonadal HormonesHormonesHormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

  • Christian Confavreux, MD

    Hospices Civils de Lyon

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 4, 2005

First Posted

August 5, 2005

Study Start

June 1, 2005

Primary Completion

April 1, 2012

Study Completion

April 1, 2012

Last Updated

December 30, 2011

Record last verified: 2011-12

Locations

FR(1)