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

Multiple Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00127075
• Other study ID #: 2004.363
• Status: Active, not recruiting
• Phase: Phase 3
• First received: August 4, 2005
• Last updated: December 28, 2011
• Start date: June 2005
• Est. completion date: April 2012

Study information

• Verified date: December 2011
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 300
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• nomegestrol acetate
10 mg/day
• estradiol
75 mcg, once a week
• placebo
matching placebo treatments

Locations

Country	Name	City	State
France	Hôpital Pierre Wertheimer	Bron

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

References & Publications (3)

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. Review. French. — View Citation

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. — View Citation

Vukusic S, Hutchinson M, Hours M, Moreau T, Cortinovis-Tourniaire P, Adeleine P, Confavreux C, The Pregnancy In Multiple Sclerosis Group; 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. Epub 2004 May 6. Erratum in: Brain. 2004 Aug;127(Pt 8):1912. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To compare the rate of relapses during the first 12 weeks after delivery, between the treated and placebo groups		12 weeks	No
Secondary	Percentage of patients who remain relapse-free during the 12-week period after delivery		12 weeks	No
Secondary	Rate of relapses, percentage of patients who remain relapse-free during the 24-week period after delivery		24 weeks	No
Secondary	Rate of relapses, percentage of patients who remain relapse-free during the 12- to 24-week period after delivery		24 weeks	No

External Links

•   European database for multiple sclerosis