Clinical trial

Cardiac Allograft Remodeling and Effects of Sirolimus on Its Progression

Name

0339-12-FB

Description

Cardiac allograft remodeling causes poor quality of life, allograft failure and increased mortality after heart transplantation. Risk factors for cardiac allograft remodeling and its progression are poorly defined and there is a need for effective interventions.This is a multi-factorial phenomenon, associated with various immunological and non-immunological factors. Animal studies suggest M-TOR inhibition attenuates cardiac allograft remodeling secondary to down-regulation of M-TOR downstream targets and increased autophagy. There is a paucity of data regarding effect of Sirolimus, a M-TOR inhibitor, on human heart remodeling. This aim of the proposal to identify the prevalence of cardiac allograft remodeling on current immunosuppressive strategies and determine risk factors for its development. It will also identify molecular pathways associated with cardiac allograft remodeling and determine the impact of Sirolimus on these pathways.

Trial arms

Trial start

2013-04-24

Estimated PCD

2018-09-27

Trial end

2018-09-27

Status

Terminated

Phase

Early phase I

Treatment

Cardiac MRI

1 month post HTx, year 1 and year 2 annual post HTx eval. CMRIs completed using 1.5-Tesla Whole Body MRI system. Scout images will determine short \& long-axis views of the heart. ECG-gated cine MR of 3 long axis and a contiguous short axis orientation will be obtained. T1-weighted delayed enhancement images will be obtained 10 minutes after injection of a gadolinium-based contrast agent. Measurements from each slice will be summed using the method of disks. Myocardial mass will be estimated by multiplying the myocardial wall volume at end diastole by the specific gravity of muscle (1.05gm/ml) and LV hypertrophy will be defined as LV mass indexed to height in meters 2.7 \>/=35.8 g/m 2.7) (18). Delayed Gadolinium enhancement will be defined as any enhancement pattern greater than 0%.

Arms:

Cardiac MRI, MTor Immunosuppression

Coronary angiography with IVUS

Coronary angiography is a test that uses dye and special x rays to show the insides of your coronary arteries. The coronary arteries supply oxygen-rich blood to your heart. Intravascular ultrasound is a test that uses sound waves to see inside blood vessels. This article discusses intravascular ultrasound to see inside the coronary arteries, the blood vessels that supply the heart.

Arms:

Coronary Angiography with IVUS, MTor Immunosuppression

Cardiac Allograft Remodeling

A surgical procedure in which a diseased heart is replaced with a healthy heart from a deceased person.

Arms:

Cardiac Allograft Remodeling, MTor Immunosuppression

Other names:

heart hypertrophy

M-TOR Immunosuppression

Sirolimus (INN/USAN), also known as rapamycin, is an immunosuppressant drug used to prevent rejection in organ transplantation; it is especially useful in kidney transplants. It prevents activation of T cells and B-cells by inhibiting their response to interleukin-2 (IL-2). Sirolimus dosage based on blood levels.

Arms:

MTor Immunosuppression

Other names:

Sirolimus

Cardiac Biopsy C4D stain

A long, thin tube called a biopsy catheter is inserted through a vein in your neck or grion and guided through your blood vessels to your heart.

Arms:

Cardiac biopsy C4D stain

Other names:

heart biopsy

Genetic Mechanism of M-TOR

To identify the molecular and genetic mechanisms associated with development of early post-transplant CAR, and to evaluate the impact of mTOR-inhibitor Sirolimus on this process.

Arms:

Genetic Mechanism of M-TOR

Cardiopulmonary Exercise Test (CPET)

The Cardiopulmonary Exercise Test is a highly sensitive, non-invasive stress test. It is considered a stress test because the exercise stresses your body's systems by making them work faster and harder. A disease or condition that affects the heart, lungs or muscles will limit how much faster and harder these systems can work. A CPET assesses how well the heart, lungs, and muscles are working individually, and how these systems are working in unison. Your heart and lungs work together to deliver oxygen to your muscles, where it is used to make energy, and to remove carbon dioxide from your body.

Arms:

Cardiopulmonary Exercise Test (CPET)

Other names:

Stress test

Size

Primary endpoint

Assessment in left ventricular hypertrophy

One year

Eligibility criteria

Inclusion Criteria: * All adult cardiac transplant recipients undergoing heart transplantation at UNMC/TNMC. Exclusion Criteria: * Adult cardiac transplant recipients with acute rejection (ISHLT R\> grade 2) or acute infection.

Protocol

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Updated at

2023-08-30

1 organization

Organization

University of Nebraska