Clinical trial NCT03102125: Allograft Dysfunction in Heart Transplant
Official title: Defining Mechanisms for Cardiac Allograft Dysfunction to Improve Allograft Longevity and Survival in Heart-Transplant Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Heart Transplant Failure and Rejection
Keywords: heart transplant
acute graft rejection
chronic graft rejection
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
First posted: 2017-04-05
Enrollment: 376
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Myocardial Perfusion Reserve
timeFrame: 60 months
Secondary outcomes:
measure: Rest and stress myocardial blood flow
timeFrame: 60 months
measure: LGE %
timeFrame: 60 months
measure: LVEF
timeFrame: 60 months
measure: LV end-diastolic volume index
timeFrame: 60 months
measure: LV mass index
timeFrame: 60 months
measure: native T1 and T2 myocardial values
timeFrame: 60 months
measure: extracellular volumes
timeFrame: 60 months
measure: myocardial strain rate
timeFrame: 60 months
Other outcomes:
measure: Major adverse cardiovascular events
timeFrame: 60 months
measure: Percentage of different T-cell subsets by single cell RNAseq
timeFrame: 60 months
measure: Number of stenotic microvasculopathy by histopathologic review of endomyocardial biopsy samples
timeFrame: 60 months
Locations:
city: La Jolla
country: United States
facility: UC San Diego
state: California
Study officials:
affiliation: UC San Diego
name: Paul Kim, MD
role: PRINCIPAL_INVESTIGATOR
References:
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