Predictors of Pregnancy Outcome in Systemic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome (APS) (PROMISSE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Hospital for Special Surgery, New York
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Hospital for Special Surgery, New York
ClinicalTrials.gov Identifier:
NCT00198068
First received: September 12, 2005
Last updated: May 28, 2014
Last verified: May 2014
  Purpose

The PROMISSE Study is an observational study of 700 pregnant patients, enrolled at nine major clinical centers. The purpose of the study is 1) to determine whether certain proteins (called complement split products) that can injure healthy organs can be used to predict poor pregnancy outcome in patients with systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS), and/or 2) to determine whether elevated levels of circulating antiangiogenic factors predict pregnancy complications in patients with aPL antibodies and/or SLE.


Condition
Systemic Lupus Erythematosus
Antiphospholipid Syndrome

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Predictors of Pregnancy Outcome in Systemic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome (APS)

Resource links provided by NLM:


Further study details as provided by Hospital for Special Surgery, New York:

Primary Outcome Measures:
  • Otherwise unexplained fetal death occurring after 12 weeks gestation [ Time Frame: End of pregnancy ] [ Designated as safety issue: No ]
    Fetal death occurring after 12 weeks' gestation and not explained by chromosomal abnormalities, anatomic malformations, or congenital infections.

  • Neonatal death prior to hospital discharge and due to complications of prematurity [ Time Frame: Time of neonatal death ] [ Designated as safety issue: No ]
  • Indicated preterm delivery prior to 36 weeks' gestation because of gestational hypertension, preeclampsia-eclampsia or placental insufficiency [ Time Frame: End of pregnancy ] [ Designated as safety issue: No ]
  • Small for gestational age (SGA) <5th %ile in the absence of anatomical or chromosomal abnormalities and/or delivery before 36 weeks because of intrauterine growth restriction (IUGR). [ Time Frame: End of pregnancy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Gestational age [ Time Frame: End of pregnancy ] [ Designated as safety issue: No ]
  • Birth weight [ Time Frame: End of pregnancy ] [ Designated as safety issue: No ]
  • Number of days neonate requires positive pressure ventilation [ Time Frame: Neonate discharge from hospital ] [ Designated as safety issue: No ]
  • Total number of days neonate is hospitalized [ Time Frame: Neonate discharge from hospital ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Serum, plasma, whole blood, RNA, urine


Estimated Enrollment: 700
Study Start Date: September 2003
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Group 1: aPL+/SLE-
Positive antiphospholipid antibodies (aPL) defined as positive LAC and/or anti cardiolipin IgG/IgM >= 40 units and/or anti-beta 2 glycoprotein I IgG or IgM >= 40 units; no SLE
Group 2: aPL+/SLE+
Positive antiphospholipid antibodies (aPL) defined as positive LAC and/or anti cardiolipin IgG/IgM >= 40 units and/or anti-beta 2 glycoprotein I IgG or IgM >= 40 units AND SLE defined as four or more American College of Rheumatology criteria for SLE.
Group 3: aPL-/SLE+
No antiphospholipid antibodies; SLE defined as four or more American College of Rheumatology criteria for SLE.
Group 4: aPL-/SLE-
Healthy controls: no antiphospholipid antibodies; no SLE

Detailed Description:

Thrombosis and pregnancy loss are common features of systemic lupus erythematosus (SLE), particularly in the presence of antiphospholipid (aPL) antibodies. The in vivo mechanisms by which aPL antibodies lead to vascular events and, specifically, to recurrent fetal loss are largely unknown. Studies in a mouse model of antiphospholipid antibody syndrome (APS) indicate that in vivo complement activation is necessary for fetal loss caused by aPL antibodies. This study represents an effort to translate these research observations on the potential role of complement activation in the pathogenesis of aPL antibody-mediated pregnancy loss to a clinically relevant human study.

In addition, studies in humans and mice have shown 1) that the balance of circulating angiogenic and antiangiogenic factors predicts preeclampsia and fetal growth restriction in healthy women, 2) circulating antiangiogenic factors cause endothelial dysfunction and abnormal placental development in animal models, and 3) complement activation leads to elevated levels of circulating antiangiogenic factors and complement inhibition prevents increased levels of antiangiogenic factors, placental dysfunction and fetal growth restriction in a mouse model of APS. This study will permit testing the hypothesis that, like in healthy women, the balance of circulating angiogenic and antiangiogenic factors predict complications in women with SLE and APS and to translate the findings in animal models into humans.

The PROMISSE Study is a prospective observational study that will follow 700 pregnant patients who will be grouped and analyzed according to the presence or absence of aPL antibodies and preexisting SLE. The patients are followed regularly during the course of the pregnancy, collecting medical and obstetrical information as well as serial blood specimens for complement and cytokine assays. The data obtained will be analyzed and used to identify mechanisms and predictors of poor fetal outcome. We expect that the insights provided through this study will suggest means to prevent, arrest or modify these conditions.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Pregnant patients identified by investigators at each study site

Criteria

Inclusion Criteria:

  • Patient pregnant with live intrauterine pregnancy, as defined by positive test for elevated β-HCG, but ≤ 12 weeks by gestation (for subjects without aPL antibodies) and ≤18 weeks (for subjects with aPL antibodies)
  • Patient between the ages of 18-45 and able to give informed consent, or age < 18 years with parental consent
  • Hematocrit > 26%
  • For APL positive:

    • aCL: IgG >= 40 GPL units; IgM >= 40 MPL units
    • Positive LAC (RVVT, Kaolin, dilute TTI or PTT LA)
    • Anti-β2GPI: IgG >= 40 GPL units; IgM >= 40 MPL units
  • For control subjects:

    • At least one successful pregnancy
    • No history of fetal death (death of conceptus ≥ 10 weeks' gestation)
    • No more than 1 miscarriage < 10 weeks' gestation
    • No history of positive aPL in local lab or positive aPL in core labs at screening
    • Not currently a smoker
    • No medical problems requiring chronic treatment

Exclusion Criteria:

  • Diabetes mellitus (Type I and Type II) antedating pregnancy
  • Multiple fetal gestations
  • Known or suspected hereditary complement deficiency (defined by CH50 = 0)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00198068

Contacts
Contact: Marta M. Guerra, MS 212-774-7361 guerram@hss.edu
Contact: Aanam Aslam, AB 212-7742115 aslama@hss.edu

Locations
United States, Illinois
University of Chicago Completed
Chicago, Illinois, United States, 60637
Northwestern University Active, not recruiting
Chicago, Illinois, United States, 60611
United States, Maryland
Johns Hopkins Hospital Active, not recruiting
Baltimore, Maryland, United States, 21287
United States, New York
NYU Langone Medical Center/Hospital for Joint Diseases Recruiting
New York, New York, United States, 10016
Contact: Aanam Aslam, AB    212-774-2115    aslama@hss.edu   
Principal Investigator: Jill P. Buyon, M.D.         
Columbia University Medical Center Completed
New York, New York, United States, 10032
Hospital for Special Surgery Recruiting
New York, New York, United States, 10021
Contact: Aanam Aslam, AB    212-774-2115    aslama@hss.edu   
Contact: Marta M Guerra, MS    212-774-7361    guerram@hss.edu   
Principal Investigator: Michael D. Lockshin, M.D.         
Principal Investigator: Lisa R. Sammaritano, M.D.         
United States, Oklahoma
Oklahoma Medical Research Foundation Active, not recruiting
Oklahoma City, Oklahoma, United States, 73104
United States, Utah
University of Utah Salt Lake City Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Vera Wünsche    801-587-0975    Vera.Wuensche@hsc.utah.edu   
Principal Investigator: Ware Branch, M.D.         
Principal Investigator: Flint Porter, M.D.         
Canada, Ontario
Mt. Sinai Hospital Recruiting
Toronto, Ontario, Canada, M5G 2K4
Contact: Karen Spitzer    416-593-6433    kspitzer@istar.ca   
Contact: Anna van Weringh    416-593-6433    avweringh@Lifequestivf.com   
Principal Investigator: Carl Laskin, M.D.         
United Kingdom
Guy's & St Thomas' NHS Foundation Trust Recruiting
London, United Kingdom, SE1 7EH
Contact: Oier Ateka, MD    +4402071883568    oier.ateka@gstt.nhs.uk   
Principal Investigator: Munther A Khamashta, MD, PhD         
Sponsors and Collaborators
Hospital for Special Surgery, New York
Investigators
Principal Investigator: Jane E. Salmon, M.D. Hospital for Special Surgery, New York
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hospital for Special Surgery, New York
ClinicalTrials.gov Identifier: NCT00198068     History of Changes
Other Study ID Numbers: 22122, R01AR049772
Study First Received: September 12, 2005
Last Updated: May 28, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Hospital for Special Surgery, New York:
Pregnancy outcomes
Systemic lupus erythematosus
Antiphospholipid syndrome

Additional relevant MeSH terms:
Syndrome
Lupus Erythematosus, Systemic
Antiphospholipid Syndrome
Disease
Pathologic Processes
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 30, 2014