Expired Study
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La Jolla, California 92037


Purpose:

The investigators will use cardiac MRI to measure the myocardial perfusion reserve and amount of myocardial edema and fibrosis in heart-transplant patients with nonspecific allograft dysfunction in contrast to those with normal graft function. The investigators hypothesize that patients with nonspecific allograft dysfunction will demonstrate decreased myocardial perfusion reserve, related to microvascular allograft vasculopathy, compared to those with normal graft function.


Study summary:

Adult heart-transplant patients, excluding those with a GFR less than 30 mL/min/1.73m2, contraindications to MRI and allergies to either regadenoson or gadolinium contrast, will be enrolled over 10 months. Patients will be recruited from UC San Diego and San Diego Veterans Affairs. The investigators will specifically enroll patients with nonspecific allograft dysfunction and patients with normal graft function. Brief protocol: Cardiac MRI is performed. Cine images in standard views are obtained. T2 mapping sequences are performed on short axis images. For stress imaging, intravenous regadenoson is given as a 0.4 mg bolus followed by a 5 mL saline flush. After 30 seconds, short-axis images are acquired for 30 consecutive heartbeats with administration of gadolinium. Rest imaging is performed 30 minutes after stress imaging. Lastly, late gadolinium enhancement images are obtained in standard views. Images are analyzed offline by a blinded independent reader. Patients will be followed for one month after enrollment for MACE.


Criteria:

Inclusion Criteria: - Age greater than or equal to 18 years old. - At least three months status post heart transplantation. - Heart-transplant patients with normal graft function (left ventricular ejection fraction equal to or greater than 55%) and no prior history of clinically significant acute rejection episodes that required modification of the immunosuppressive regimen or cardiac allograft vasculopathy. - Heart-transplant patients with nonspecific allograft dysfunction (left ventricular ejection fraction equal to or less than 50% AND decrease from post-transplant baseline ejection fraction by an absolute difference of 10% or greater, no formal diagnosis of allograft vasculopathy by coronary angiogram or coronary vascular ultrasonography, and no history of prior acute rejection episodes known to have decreased left ventricular ejection fraction to or less than 50%). Exclusion Criteria: - Biopsy proven acute rejection episode in the past 3 months. - Patients with symptoms or signs of acute myocardial ischemia or recent acute coronary syndrome in the past 3 months. - Uncontrolled obstructive ventilatory disease including asthma and COPD. - Second or third degree AV nodal block. - Sinus node dysfunction. - Contraindications to MRI including pacemakers or implantable cardioverter-defibrillators. - Renal dysfunction with an estimated GFR less than 30 mL/min/1.73m2. - Prior adverse reaction to either regadenoson or gadolinium contrast. Prior adverse reaction to adenosine will be assessed on a case-by-case basis. - Any invasive procedure, including endomyocardial biopsy and left coronary angiogram, performed within one week. - Systolic blood pressure greater than 180 or less than 85 mmHg. - Diastolic blood pressure greater than 120 or less than 40 mmHg. - Resting heart rate greater than 120 or less than 45 beats per minute. - Severe claustrophobia.


Study is Available At:


Original ID:

1186278


NCT ID:

NCT02597543


Secondary ID:


Study Acronym:


Brief Title:

Stress Cardiac MRI for Evaluation of Nonspecific Allograft Dysfunction


Official Title:

Stress Cardiac MRI Using Regadenoson for Evaluation of Nonspecific Allograft Dysfunction


Overall Status:

Completed


Study Phase:

Phase 4


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Stanford University


Oversight Authority:

United States: Institutional Review Board


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

2


Number of Groups:

0


Total Enrollment:

18


Enrollment Type:

Anticipated


Overall Contact Information

Official Name:Paul J Kim, MD
Principal Investigator
Stanford University

Study Dates

Start Date:November 2015
Completion Date:June 30, 2016
Completion Type:Actual
Primary Completion Date:June 30, 2016
Primary Completion Type:Actual
Verification Date:May 2017
Last Changed Date:May 31, 2017
First Received Date:October 30, 2015

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Mean segmental T1 values of the left ventricle
Time Frame:10 months
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Late gadolinium enhancement
Time Frame:10 months
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:All cause mortality
Time Frame:10 months
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Death from cardiovascular causes
Time Frame:10 months
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Re-transplantation
Time Frame:10 months
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Hospitalization for cardiac related causes
Time Frame:10 months
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Myocardial ischemia/infarction
Time Frame:10 months
Safety Issues:False
Outcome Type:Primary Outcome
Measure:Myocardial perfusion reserve
Time Frame:10 months
Safety Issues:False

Study Interventions

Intervention Type:Drug
Name:Regadenoson
Description:For use in stress myocardial perfusion imaging.
Arm Name:Nonspecific allograft dysfunction
Other Name:Lexiscan
Intervention Type:Drug
Name:Gadolinium
Description:For use in both perfusion imaging and late gadolinium enhancement.
Arm Name:Nonspecific allograft dysfunction
Other Name:Magnevist
Intervention Type:Procedure
Name:Cardiac MRI
Description:Cardiac MRI will be the imaging modality for perfusion imaging, late gadolinium enhancement and obtaining mean T1 segmental values of the heart.
Arm Name:Nonspecific allograft dysfunction

Study Arms

Study Arm Type:Experimental
Arm Name:Normal graft function
Description:Patients with normal graft function will undergo stress cardiac MRI with regadenoson in addition to performing late gadolinium enhancement and obtaining mean segmental T1 values of the heart.
Study Arm Type:Experimental
Arm Name:Nonspecific allograft dysfunction
Description:Patients with nonspecific allograft dysfunction will undergo stress cardiac MRI with regadenoson in addition to performing late gadolinium enhancement and obtaining mean segmental T1 values of the heart.

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Paul Kim
Agency Class:Industry
Agency Type:Collaborator
Agency Name:Astellas Pharma Inc

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Reference
Citation:Solberg OG, Ragnarsson A, Kvarsnes A, Endresen K, Kongsgård E, Aakhus S, Gullestad L, Stavem K, Aaberge L. Reference interval for the index of coronary microvascular resistance. EuroIntervention. 2014 Jan 22;9(9):1069-75. doi: 10.4244/EIJV9I9A181.
PMID:24457279
Reference Type:Reference
Citation:Kübrich M, Petrakopoulou P, Kofler S, Nickel T, Kaczmarek I, Meiser BM, Reichart B, von Scheidt W, Weis M. Impact of coronary endothelial dysfunction on adverse long-term outcome after heart transplantation. Transplantation. 2008 Jun 15;85(11):1580-7. doi: 10.1097/TP.0b013e318170b4cd.
PMID:18551063
Reference Type:Reference
Citation:Butler CR, Thompson R, Haykowsky M, Toma M, Paterson I. Cardiovascular magnetic resonance in the diagnosis of acute heart transplant rejection: a review. J Cardiovasc Magn Reson. 2009 Mar 12;11:7. doi: 10.1186/1532-429X-11-7. Review.
PMID:19284612
Reference Type:Reference
Citation:Marie PY, Angioï M, Carteaux JP, Escanye JM, Mattei S, Tzvetanov K, Claudon O, Hassan N, Danchin N, Karcher G, Bertrand A, Walker PM, Villemot JP. Detection and prediction of acute heart transplant rejection with the myocardial T2 determination provided by a black-blood magnetic resonance imaging sequence. J Am Coll Cardiol. 2001 Mar 1;37(3):825-31.
PMID:11693758
Reference Type:Reference
Citation:Miller CA, Sarma J, Naish JH, Yonan N, Williams SG, Shaw SM, Clark D, Pearce K, Stout M, Potluri R, Borg A, Coutts G, Chowdhary S, McCann GP, Parker GJ, Ray SG, Schmitt M. Multiparametric cardiovascular magnetic resonance assessment of cardiac allograft vasculopathy. J Am Coll Cardiol. 2014 Mar 4;63(8):799-808. doi: 10.1016/j.jacc.2013.07.119. Epub 2013 Dec 18.
PMID:24355800
Reference Type:Reference
Citation:Bhalodolia R, Cortese C, Graham M, Hauptman PJ. Fulminant acute cellular rejection with negative findings on endomyocardial biopsy. J Heart Lung Transplant. 2006 Aug;25(8):989-92. Epub 2006 Jun 30.
PMID:16890123
Reference Type:Reference
Citation:Pham MX, Teuteberg JJ, Kfoury AG, Starling RC, Deng MC, Cappola TP, Kao A, Anderson AS, Cotts WG, Ewald GA, Baran DA, Bogaev RC, Elashoff B, Baron H, Yee J, Valantine HA; IMAGE Study Group.. Gene-expression profiling for rejection surveillance after cardiac transplantation. N Engl J Med. 2010 May 20;362(20):1890-900. doi: 10.1056/NEJMoa0912965. Epub 2010 Apr 22.
PMID:20413602
Reference Type:Reference
Citation:Fang JC, Kinlay S, Beltrame J, Hikiti H, Wainstein M, Behrendt D, Suh J, Frei B, Mudge GH, Selwyn AP, Ganz P. Effect of vitamins C and E on progression of transplant-associated arteriosclerosis: a randomised trial. Lancet. 2002 Mar 30;359(9312):1108-13.
PMID:11943259
Reference Type:Reference
Citation:Uretsky BF, Murali S, Reddy PS, Rabin B, Lee A, Griffith BP, Hardesty RL, Trento A, Bahnson HT. Development of coronary artery disease in cardiac transplant patients receiving immunosuppressive therapy with cyclosporine and prednisone. Circulation. 1987 Oct;76(4):827-34.
PMID:3308166
Reference Type:Reference
Citation:Costanzo MR, Dipchand A, Starling R, Anderson A, Chan M, Desai S, Fedson S, Fisher P, Gonzales-Stawinski G, Martinelli L, McGiffin D, Smith J, Taylor D, Meiser B, Webber S, Baran D, Carboni M, Dengler T, Feldman D, Frigerio M, Kfoury A, Kim D, Kobashigawa J, Shullo M, Stehlik J, Teuteberg J, Uber P, Zuckermann A, Hunt S, Burch M, Bhat G, Canter C, Chinnock R, Crespo-Leiro M, Delgado R, Dobbels F, Grady K, Kao W, Lamour J, Parry G, Patel J, Pini D, Towbin J, Wolfel G, Delgado D, Eisen H, Goldberg L, Hosenpud J, Johnson M, Keogh A, Lewis C, O'Connell J, Rogers J, Ross H, Russell S, Vanhaecke J; International Society of Heart and Lung Transplantation Guidelines.. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. J Heart Lung Transplant. 2010 Aug;29(8):914-56. doi: 10.1016/j.healun.2010.05.034.
PMID:20643330
Reference Type:Reference
Citation:Berry GJ, Angelini A, Burke MM, Bruneval P, Fishbein MC, Hammond E, Miller D, Neil D, Revelo MP, Rodriguez ER, Stewart S, Tan CD, Winters GL, Kobashigawa J, Mehra MR. The ISHLT working formulation for pathologic diagnosis of antibody-mediated rejection in heart transplantation: evolution and current status (2005-2011). J Heart Lung Transplant. 2011 Jun;30(6):601-11. doi: 10.1016/j.healun.2011.02.015.
PMID:21555100
Reference Type:Reference
Citation:Stehlik J, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, Dobbels F, Kirk R, Rahmel AO, Hertz MI. The Registry of the International Society for Heart and Lung Transplantation: Twenty-eighth Adult Heart Transplant Report--2011. J Heart Lung Transplant. 2011 Oct;30(10):1078-94. doi: 10.1016/j.healun.2011.08.003.
PMID:21962016

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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