NCT03102125

Brief 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
376

participants targeted

Target at P75+ for phase_4

Timeline
8mo left

Started Oct 2019

Longer than P75 for phase_4

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress91%
Oct 2019Jan 2027

First Submitted

Initial submission to the registry

March 29, 2017

Completed
7 days until next milestone

First Posted

Study publicly available on registry

April 5, 2017

Completed
2.5 years until next milestone

Study Start

First participant enrolled

October 1, 2019

Completed
7.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2027

Expected
1 day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 2, 2027

Last Updated

May 1, 2026

Status Verified

April 1, 2026

Enrollment Period

7.3 years

First QC Date

March 29, 2017

Last Update Submit

April 27, 2026

Conditions

Heart Transplant Failure and Rejection

Keywords

heart transplantacute graft rejectionchronic graft rejection

Outcome Measures

Primary Outcomes (1)

  • Myocardial Perfusion Reserve

    60 months

Secondary Outcomes (8)

  • Rest and stress myocardial blood flow

    60 months

  • LGE %

    60 months

  • LVEF

    60 months

  • LV end-diastolic volume index

    60 months

  • LV mass index

    60 months

  • +3 more secondary outcomes

Other Outcomes (3)

  • Major adverse cardiovascular events

    60 months

  • Percentage of different T-cell subsets by single cell RNAseq

    60 months

  • Number of stenotic microvasculopathy by histopathologic review of endomyocardial biopsy samples

    60 months

Study Arms (4)

Nonspecific allograft dysfunction

EXPERIMENTAL

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. Peripheral blood and endomycardial biopsies will also be obtained for single cell RNAseq analyses.

Drug: Regadenoson

Normal graft function

EXPERIMENTAL

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. Peripheral blood and endomycardial biopsies will also be obtained for single cell RNAseq analyses.

Drug: Regadenoson

Cardiac allograft vasculopathy

EXPERIMENTAL

Patients with allograft dysfunction from known cardiac 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. Peripheral blood and endomycardial biopsies will also be obtained for single cell RNAseq analyses.

Drug: Regadenoson

ACR/AMR

EXPERIMENTAL

Patients with allograft dysfunction from prior episodes of acute cellular or antibody mediated rejection will undergo stress cardiac MRI with regadenoson in addition to performing late gadolinium enhancement and obtaining mean segmental T1 values of the heart. Peripheral blood and endomycardial biopsies will also be obtained for single cell RNAseq analyses.

Drug: Regadenoson

Interventions

RegadenosonDRUG

For use in stress myocardial perfusion imaging.

Also known as: Lexiscan
ACR/AMRCardiac allograft vasculopathyNonspecific allograft dysfunctionNormal graft function

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age greater than or equal to 18 years old.
  • At least three months status post heart transplantation.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

UC San Diego

La Jolla, California, 92037, United States

RECRUITING

Related Publications (12)

  • 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. No abstract available.

    PMID: 21962016RESULT

  • 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. No abstract available.

    PMID: 21555100RESULT

  • 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. No abstract available.

    PMID: 20643330RESULT

  • 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. doi: 10.1161/01.cir.76.4.827.

    PMID: 3308166RESULT

  • 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. doi: 10.1016/S0140-6736(02)08154-0.

    PMID: 11943259RESULT

  • 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: 20413602RESULT

  • 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.

    PMID: 16890123RESULT

  • 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: 24355800RESULT

  • 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 by a black-blood magnetic resonance imaging sequence. J Am Coll Cardiol. 2001 Mar 1;37(3):825-31. doi: 10.1016/s0735-1097(00)01196-7.

    PMID: 11693758RESULT

  • 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.

    PMID: 19284612RESULT

  • 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: 10.1097/TP.0b013e318170b4cd.

    PMID: 18551063RESULT

  • 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.

    PMID: 24457279RESULT

MeSH Terms

Conditions

Rejection, Psychology

Interventions

regadenoson

Condition Hierarchy (Ancestors)

Social BehaviorBehavior

Study Officials

  • Paul Kim, MD

    UC San Diego

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Paul Kim, MD

CONTACT

8582460638pjk017@ucsd.edu

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NON RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
DIAGNOSTIC
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Assistant Professor

Study Record Dates

First Submitted

March 29, 2017

First Posted

April 5, 2017

Study Start

October 1, 2019

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

January 2, 2027

Last Updated

May 1, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will not share

Locations

US(1)