Is a History of Pre-eclampsia a Risk Factor for Vascular Phenotype in Women With Systemic Sclerosis?

NCT04363021 | Completed DMC

• 1 other identifier: PREVASCLERO (29BRC20.0080)
• Study Type: observational
• Target: 378
• Locations: 1 country
• Sites: 10

Brief Summary

Background: Pre-eclampsia, defined by the association of an arterial hypertension and significant proteinuria after 20 weeks of gestation, complicates 1 to 2% of pregnancies in France. Its pathophysiology involves angiogenesis impairment, upregulated maternal systemic inflammatory response, activation of oxidative stress and endothelial dysfunction. In a recent Danish nation-wide cohort study, pre-eclampsia was associated with a 69% increased risk of later developing scleroderma. Type of study: prospective observational case-control study. Primary objective of the study: to determine if a history of pre-eclampsia before systemic sclerosis diagnosis is an independent risk factor for vascular phenotype in sclerodermic women. Secondary objective: to describe all risk factors for vascular phenotype in sclerodermic women with a previous pregnancy longer than 6 months before scleroderma diagnosis.

Conditions

Systemic Sclerosis; Preeclampsia; Vascular Complications

Keywords

systemic sclerosis; vascular phenotype; pre-eclampsia

Outcome Measures

Primary Outcomes (1)

• History of pre-eclampsia before systemic sclerosis diagnosis

  Primary outcome will be evaluated by the proportion of women with a history of pre-eclampsia before systemic sclerosis diagnosis in each group. Primary judgement criterion will be the response of a woman to the " pre-eclampsia questionnaire ". The aim is to determine if a history of pre-eclampsia before systemic sclerosis diagnosis is an independent prognostic factor for vascular phenotype in sclerodermic women. Primary judgement criterion: Responses of the women to the " pre-eclampsia questionnaire ".

  Inclusion (Day 0)

Secondary Outcomes (1)

• Risk factors for vascular phenotype in sclerodermic women with a previous pregnancy longer than 6 months

  Inclusion (Day 0)

Study Arms (2)

cases

Cases will be defined as women with systemic sclerosis, specific vascular complications (digital ulcers, specific cardiac involvement of systemic sclerosis including pulmonary arterial hypertension, renal crisis) and with a previous pregnancy longer than 6 months before systemic sclerosis diagnosis.

controls

Controls will be defined as women with systemic sclerosis, no specific vascular complication and with a previous pregnancy longer than 6 months before systemic sclerosis diagnosis.

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: female
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Women with a diagnosis of systemic sclerosis according to EULAR 2013 diagnostic criteria AND with a history of pregnancy longer than 6 months (28 WG) before systemic sclerosis diagnosis followed in one of the French centers of expertise for systemic sclerosis will be offered to participate to the study during the annual follow-up consultation with her referring physician.

You may qualify if:

• General:
• Women with a diagnosis of systemic sclerosis according to EULAR 2013 diagnostic criteria AND with a history of pregnancy longer than 6 months (28 weeks of gestation (WG)) before systemic sclerosis diagnosis.
• Specific:
• For the women of the " case " group :
• Women with vascular complications specific of systemic sclerosis (digital ulcers, specific cardiac involvement of systemic sclerosis including pulmonary arterial hypertension, renal crisis).
• For the women of the " control " group :
• Women with no vascular complications specific of systemic sclerosis.
• Refusal to participate to the study
• Minor women
• Women under tutorship
• Women with no pregnancy history or with a history of pregnancy(ies) below 6 months length.

You may not qualify if:

• Women aged of less than 18 years
• Women on legal protection
• Women with no history of pregnancy of more than 6 months
• Women unable to fill out a questionnaire in French
• Women who refuse to participate to the study

Sponsors & Collaborators

• University Hospital, Brest: lead

Study Sites (10)

CHU de Clermont-Ferrand

Clermont-Ferrand, 63003, France

Location

CHU de Dijon

Dijon, 21079, France

Location

CHU de Lille

Lille, 59037, France

Location

CHU de Limoges

Limoges, 87042, France

Location

CHU de Nantes

Nantes, 44093, France

Location

CHU de Nice

Nice, 06200, France

Location

CHU de Rennes

Rennes, 35000, France

Location

CHU de Strasbourg

Strasbourg, 67200, France

Location

CHU de Toulouse

Toulouse, 31059, France

Location

CHU de Tours

Tours, 37044, France

Location

Related Publications (24)

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• Conrad KP, Miles TM, Benyo DF. Circulating levels of immunoreactive cytokines in women with preeclampsia. Am J Reprod Immunol. 1998 Aug;40(2):102-11. doi: 10.1111/j.1600-0897.1998.tb00398.x.

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• Redman CW, Sargent IL. Pre-eclampsia, the placenta and the maternal systemic inflammatory response--a review. Placenta. 2003 Apr;24 Suppl A:S21-7. doi: 10.1053/plac.2002.0930.

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• Zhou CC, Zhang Y, Irani RA, Zhang H, Mi T, Popek EJ, Hicks MJ, Ramin SM, Kellems RE, Xia Y. Angiotensin receptor agonistic autoantibodies induce pre-eclampsia in pregnant mice. Nat Med. 2008 Aug;14(8):855-62. doi: 10.1038/nm.1856. Epub 2008 Jul 27.

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• Herse F, Verlohren S, Wenzel K, Pape J, Muller DN, Modrow S, Wallukat G, Luft FC, Redman CW, Dechend R. Prevalence of agonistic autoantibodies against the angiotensin II type 1 receptor and soluble fms-like tyrosine kinase 1 in a gestational age-matched case study. Hypertension. 2009 Feb;53(2):393-8. doi: 10.1161/HYPERTENSIONAHA.108.124115. Epub 2008 Dec 8.

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• Lim R, Acharya R, Delpachitra P, Hobson S, Sobey CG, Drummond GR, Wallace EM. Activin and NADPH-oxidase in preeclampsia: insights from in vitro and murine studies. Am J Obstet Gynecol. 2015 Jan;212(1):86.e1-12. doi: 10.1016/j.ajog.2014.07.021. Epub 2014 Jul 18.

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• Roberts JM, Taylor RN, Musci TJ, Rodgers GM, Hubel CA, McLaughlin MK. Preeclampsia: an endothelial cell disorder. Am J Obstet Gynecol. 1989 Nov;161(5):1200-4. doi: 10.1016/0002-9378(89)90665-0.

  PMID: 2589440 BACKGROUND

• Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. BMJ. 2007 Nov 10;335(7627):974. doi: 10.1136/bmj.39335.385301.BE. Epub 2007 Nov 1.

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• Kamper-Jorgensen M, Gammill HS, Nelson JL. Preeclampsia and scleroderma: a prospective nationwide analysis. Acta Obstet Gynecol Scand. 2018 May;97(5):587-590. doi: 10.1111/aogs.13296. Epub 2018 Feb 8.

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• van Wyk L, van der Marel J, Schuerwegh AJ, Schouffoer AA, Voskuyl AE, Huizinga TW, Bianchi DW, Scherjon SA. Increased incidence of pregnancy complications in women who later develop scleroderma: a case control study. Arthritis Res Ther. 2011;13(6):R183. doi: 10.1186/ar3510. Epub 2011 Nov 4.

  PMID: 22053948 BACKGROUND

• Englert H, Small-McMahon J, Davis K, O'Connor H, Chambers P, Brooks P. Systemic sclerosis prevalence and mortality in Sydney 1974-88. Aust N Z J Med. 1999 Feb;29(1):42-50. doi: 10.1111/j.1445-5994.1999.tb01587.x.

  PMID: 10200812 BACKGROUND

• Lee P, Langevitz P, Alderdice CA, Aubrey M, Baer PA, Baron M, Buskila D, Dutz JP, Khostanteen I, Piper S, et al. Mortality in systemic sclerosis (scleroderma). Q J Med. 1992 Feb;82(298):139-48.

  PMID: 1620814 BACKGROUND

• Simeon CP, Armadans L, Fonollosa V, Solans R, Selva A, Villar M, Lima J, Vaque J, Vilardell M. Mortality and prognostic factors in Spanish patients with systemic sclerosis. Rheumatology (Oxford). 2003 Jan;42(1):71-5. doi: 10.1093/rheumatology/keg033.

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• Jacobsen S, Halberg P, Ullman S. Mortality and causes of death of 344 Danish patients with systemic sclerosis (scleroderma). Br J Rheumatol. 1998 Jul;37(7):750-5. doi: 10.1093/rheumatology/37.7.750.

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• van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, Matucci-Cerinic M, Naden RP, Medsger TA Jr, Carreira PE, Riemekasten G, Clements PJ, Denton CP, Distler O, Allanore Y, Furst DE, Gabrielli A, Mayes MD, van Laar JM, Seibold JR, Czirjak L, Steen VD, Inanc M, Kowal-Bielecka O, Muller-Ladner U, Valentini G, Veale DJ, Vonk MC, Walker UA, Chung L, Collier DH, Csuka ME, Fessler BJ, Guiducci S, Herrick A, Hsu VM, Jimenez S, Kahaleh B, Merkel PA, Sierakowski S, Silver RM, Simms RW, Varga J, Pope JE. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum. 2013 Nov;65(11):2737-47. doi: 10.1002/art.38098. Epub 2013 Oct 3.

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• Riemekasten G, Philippe A, Nather M, Slowinski T, Muller DN, Heidecke H, Matucci-Cerinic M, Czirjak L, Lukitsch I, Becker M, Kill A, van Laar JM, Catar R, Luft FC, Burmester GR, Hegner B, Dragun D. Involvement of functional autoantibodies against vascular receptors in systemic sclerosis. Ann Rheum Dis. 2011 Mar;70(3):530-6. doi: 10.1136/ard.2010.135772. Epub 2010 Nov 15.

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• Walther T, Wallukat G, Jank A, Bartel S, Schultheiss HP, Faber R, Stepan H. Angiotensin II type 1 receptor agonistic antibodies reflect fundamental alterations in the uteroplacental vasculature. Hypertension. 2005 Dec;46(6):1275-9. doi: 10.1161/01.HYP.0000190040.66563.04. Epub 2005 Oct 31.

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• Nelson JL, Furst DE, Maloney S, Gooley T, Evans PC, Smith A, Bean MA, Ober C, Bianchi DW. Microchimerism and HLA-compatible relationships of pregnancy in scleroderma. Lancet. 1998 Feb 21;351(9102):559-62. doi: 10.1016/S0140-6736(97)08357-8.

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• Allanore Y, Distler O, Matucci-Cerinic M, Denton CP. Review: Defining a Unified Vascular Phenotype in Systemic Sclerosis. Arthritis Rheumatol. 2018 Feb;70(2):162-170. doi: 10.1002/art.40377. Epub 2018 Jan 22.

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• Lescoat A, Yelnik CM, Coiffier G, Wargny M, Lamotte C, Cazalets C, Belhomme N, Ballerie A, Hatron PY, Launay D, Perdriger A, Sobanski V, Hachulla E, Jego P. Ulnar Artery Occlusion and Severity Markers of Vasculopathy in Systemic Sclerosis: A Multicenter Cross-Sectional Study. Arthritis Rheumatol. 2019 Jun;71(6):983-990. doi: 10.1002/art.40799. Epub 2019 Apr 29.

  PMID: 30552835 BACKGROUND

• Diehl CL, Brost BC, Hogan MC, Elesber AA, Offord KP, Turner ST, Garovic VD. Preeclampsia as a risk factor for cardiovascular disease later in life: validation of a preeclampsia questionnaire. Am J Obstet Gynecol. 2008 May;198(5):e11-3. doi: 10.1016/j.ajog.2007.09.038. Epub 2008 Feb 1.

  PMID: 18241822 BACKGROUND

MeSH Terms

Conditions

Scleroderma, Systemic; Pre-Eclampsia

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2020
• First Posted: April 27, 2020
• Study Start: July 6, 2020
• Primary Completion: May 31, 2022
• Study Completion: May 31, 2022
• Last Updated: February 9, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be available beginning two year and ending five years following the end study
• Access Criteria: Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement.

Locations

FR (10)