Allograft Dysfunction in Heart Transplant

Heart Transplant Failure and Rejection Clinical Trial

Official title:

Defining Mechanisms for Cardiac Allograft Dysfunction to Improve Allograft Longevity and Survival in Heart-Transplant Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03102125
• Other study ID #: 160808
• Status: Recruiting
• Phase: Phase 4
• Start date: October 1, 2019
• Est. completion date: December 2, 2024

Study information

• Verified date: January 2024
• Source: University of California, San Diego
• Contact: Paul Kim, MD
• Phone: 8582460638
• Email: pjk017[@]ucsd.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators will evaluate for early evidence of cardiac allograft dysfunction by cardiac MRI and single cell sequencing to determine underlying molecular and macroscopic causes.

Description:

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 60 months. Patients will be recruited from UCSD. The investigators will specifically enroll all eligible heart-transplant patients.

Brief protocol:

Cardiac MRI is performed. Cine images in standard views are obtained. T1 and T2 mapping sequences are performed on short axis images pre- and post-gadolinium contrast. 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 at least 1 year after enrollment for MACE.

Peripheral blood and endomyocardial biopsies will also be collected, timing as per usual clinical care as well as for-cause, for single cell RNAseq analyses.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 376
• Est. completion date: December 2, 2024
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age greater than or equal to 18 years old.

• At least three months status post heart transplantation.

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.

• History of generalized tonic-clonic seizures.

• Second or third degree AV nodal block.

• Sinus node dysfunction.

• Contraindications to MRI including cardiovascular implantable electronic devices.

• 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 or dipyridamole will be assessed on a case-by-case basis.

• 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.

Related Conditions & MeSH terms

• Heart Transplant Failure and Rejection

Intervention

Drug:
• Regadenoson
For use in stress myocardial perfusion imaging.

Locations

Country	Name	City	State
United States	UC San Diego	La Jolla	California

Sponsors (1)

Lead Sponsor	Collaborator
Paul Kim

Country where clinical trial is conducted

United States, 

References & Publications (12)

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 — View 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. doi: 10.1016/j.healun.2006.04.002. Epub 2006 Jun 30. — View 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(1):7. doi: 10.1186/1532-429X-11-7. — View 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 — View 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. d — View Citation

Kubrich 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 — View Citation

Marie PY, Angioi 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 b — View 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 v — View 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 cardia — View Citation

Solberg OG, Ragnarsson A, Kvarsnes A, Endresen K, Kongsgard 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. — View 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 — View 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 O — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Major adverse cardiovascular events	death, re-transplantation, percutaneous coronary intervention and HF hospitalization	60 months
Other	Percentage of different T-cell subsets by single cell RNAseq		60 months
Other	Number of stenotic microvasculopathy by histopathologic review of endomyocardial biopsy samples	Each endomyocardial biopsy slide will be reviewed for stenotic microvasculopathy as per Hiemann et al 2007, Circulation. 1 stenotic blood vessel per view on X200 zoom is diagnostic of stenotic microvasculopathy.	60 months
Primary	Myocardial Perfusion Reserve		60 months
Secondary	Rest and stress myocardial blood flow		60 months
Secondary	LGE %		60 months
Secondary	LVEF		60 months
Secondary	LV end-diastolic volume index		60 months
Secondary	LV mass index		60 months
Secondary	native T1 and T2 myocardial values		60 months
Secondary	extracellular volumes		60 months
Secondary	myocardial strain rate		60 months