Investigation in Pregnancy Associate Cardiomyopathy

Pregnancy Clinical Trial

— IPAC  

Official title:

Immune Activation and Myocardial Recovery in Peripartum Cardiomyopathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01085955
• Other study ID #: IPAC
• Status: Completed
• Phase: N/A
• First received: March 10, 2010
• Last updated: January 14, 2016
• Start date: October 2009
• Est. completion date: August 2014

Study information

• Verified date: January 2016
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

Peri-partum cardiomyopathy is a heart muscle weakness that occurs during or following pregnancy. Research suggests that many initial heart injuries including viruses, pregnancy and other unknown causes, can lead to a process of inflammation of the heart muscle which can weaken the heart and cause cardiomyopathy. Why this process occurs in women during pregnancy is not well understood and if it differs from those women who develop cardiomyopathy from a virus is unknown. This study has been proposed to look at genetic information (DNA) as well as the immune system (the body's response to fight off infections and/or viruses) to find possible causes for the heart muscle damage that occurs in peripartum cardiomyopathy.

Description:

Specific Aim 1: Evaluate systemic immune activation as the etiology of PPCM. We will determine a) the degree of immune activation in PPCM and b) the relationship of autoimmunity to left ventricular dysfunction and time course of myocardial recovery, in 100 women enrolled at 30 centers. Subjects will have blood drawn for assessment of autoantibodies, and cellular immune activation at presentation, 2 month and 6 month postpartum, and will have assessment of LVEF by transthoracic echo at presentation, 2 months, 6 months and 12 months post partum. This aim will explore the hypothesis that more prolonged activation of the cellular and/or humoral immune system is associated with greater likelihood of persistent chronic cardiomyopathy.

In addition this aim will determine genetic and clinical predictors of LV recovery, and evaluate racial differences in presentation, remodeling and recovery. This study will evaluate the echo parameters of dysynchrony, diastolic function, LV size and volumes to determine echo predictors of subsequent recovery. In addition racial differences in presentation, remodeling and recovery will be investigated.

Specific Aim 2: Investigate frequency of myocardial injury or inflammation on cardiac MRI and the ability of tissue characteristics to predict subsequent recovery of LVEF. Cardiac MRI with gadolinium enhancement will be performed in 50 subjects with PPCM from Aim 1 at presentation and repeated at 6 months post partum. We will test the hypothesis is that subjects with more extensive injury (defined as % myocardium with late gadolinium enhancement) will have less recovery at 6 months.

Specific Aim 3: Establish DNA and serum to facilitate future investigations of the pathogenesis of peripartum cardiomyopathy. All subjects enrolled will have DNA, RNA from peripheral blood and serum banked at entry. Serum will be repeated at 2 and 6 months post partum.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• Patient of 16 years of age or older

• Diagnosis of peripartum cardiomyopathy

• Presentation for enrollment no earlier than one month pre-term and no later than two months post partum.

• LVEF less than OR equal to 0.45 by echocardiogram

Additional inclusion criteria for MRI substudy:

• Must be post partum

• Participant is not breast feeding or is willing to forego breast feeding for 24 hours post gadolinium.

Exclusion Criteria:

• Previous diagnosis of cardiomyopathy, valvular disease or complex congenital heart disease

• Evidence of CAD (>50% stenosis of major epicardial vessel or positive non-invasive stress test)

• Previous cardiac transplant

• Chemotherapy or chest radiation within 5 years of enrollment

• Evidence of ongoing bacterial septicemia (positive blood cultures)

• Medical, social, or psychiatric condition which limit the ability to comply with follow-up (Example: alcohol or drug abuse)

Additional Exclusion for MRI Substudy

• GFR < 30mL/1.7 m2 by MDRD equation (http://www.kidney.org/professionals/kdogi/gfr_calculator.cfm)

• Currently breast feeding or unwilling to forego for 24 hour period post gadolinium

• Implanted devices (cochlear implants, pacemakers, defibrillators, infusion pumps, nerve stimulators, etc)

• Cerebral aneurysm clips

• Swan Ganz catheter or intra aortic balloon pump

• Ocular metal or metallic splinters in the eye

• Pregnant women

• Metal shrapnel or bullet

• Allergy to Gadolinium

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy
• Pregnancy

Locations

Country	Name	City	State
Canada	Foothills Medical Center	Calgary	Alberta
Canada	Sir Mortimer B. Davis / Jewish General Hospital	Montreal	Quebec
United States	Medical College of Georgia	Augusta	Georgia
United States	Johns Hopkins	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	Brigham and Women's	Boston	Massachusetts
United States	Massachusetts General	Boston	Massachusetts
United States	University of Illinois	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	University of Texas, Southwestern	Dallas	Texas
United States	DMC Cardiovascular Institute / Harper University Hospital	Detroit	Michigan
United States	Duke University	Durham	North Carolina
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Baylor College of Medicine	Houston	Texas
United States	University of Kentucky	Lexington	Kentucky
United States	University of Southern California	Los Angeles	California
United States	Louisiana State University Health Science Center	Louisiana	Louisiana
United States	University of Miami, Miller School of Medicine	Miami	Florida
United States	Gagnon Cardiovascular Institute at Morristown Memorial Hospital	Morristown	New Jersey
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Columbia University	New York City	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester Medical Center	Rochester	New York
United States	Intermountain Medical Center	Salt Lake City	Utah
United States	Washington University	St. Louis	Missouri
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Wake Forest University	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of Pittsburgh	National Institutes of Health (NIH)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Long Term Survival Data	We are asking women to extend thier consent for 5 additional years from thier delivery date to collect survival data (alive, transplanted, VAD implanted; medications; NYAH Class; subsequent pregnancies)	up to 5 years	No
Primary	Evaluate systemic immune activation as the etiology of PPCM	determine the degree of immune activation in PPCM and the relationship of autoimmunity to left ventricular dysfunction and time course of myocardial recovery, in 100 women enrolled at multiple centers.	6-12 months	No
Secondary	Investigate frequency of myocardial injury or inflammation on cardiac MRI and the ability of tissue characteristics to predict subsequent recovery of LVEF	Cardiac MRI with gadolinium enhancement will be performed in 50 subjects with PPCM from Aim 1 at presentation and repeated at 6 months post partum. We will test the hypothes that subjects with more extensive injury (defined as % myocardium with late gadolinium enhancement) will have less recovery at 6 months	6 months	No