Effect of Chronic Inflammation on Myocardial Perfusion and Function

Sponsor

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Overall Status

Recruiting

CT.gov ID

NCT04870827

Collaborator

(none)

168

Enrollment

Location

48.8

Anticipated Duration (Months)

3.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Background:

Heart failure (HF) is a public health burden. Studies have shown a link between inflammation, myocardial dysfunction, and HF. Researchers want to use psoriasis as a disease model of chronic inflammation to further study the link between inflammation and myocardial dysfunction.

Objective:

To learn if chronic inflammation affects the heart and if taking a biological medicine for chronic inflammation helps improve how the heart works.

Eligibility:

Adults ages 18 and older who have moderate to severe psoriasis, and healthy adult volunteers.

Design:

Participants will be screened with a medical history. They may take a pregnancy test.

Healthy volunteers will have 1 visit. Those with psoriasis will have a second visit 1 year later.

Participants may give blood samples. They may have a heart function test. They may have a heart imaging test, and may get a contrast agent. If so, it will be injected into a vein.

Participants may have positron emission tomography/computed tomography tests. They will lie on their back on a padded table with their arms straight overhead. They may get radioactive drugs through an intravenous (IV) catheter. They will get stress medicines through the IV. These drugs mimic exercise and increase blood flow through the heart.

Participants may have cardiac magnetic resonance imaging. The scanner is a large tube. Participants will lie on a table that slides in and out of the tube. They will get gadolinium contrast in a vein to improve the pictures. They may get stress medicines. Coils will be used to help make the pictures.

Participation for healthy volunteers will last 1-2 days. Participation for those with psoriasis will last 14 months.

...

Condition or Disease	Intervention/Treatment	Phase
Psoriasis

Detailed Description

Study Description:

Heart failure (HF) remains a significant public health burden despite expanding and improving treatment options. Clinical and pre-clinical studies have demonstrated compelling relationships between inflammation, myocardial dysfunction, HF and adverse clinical outcomes. In this study to be conducted at the NIH Clinical Center, we propose to utilize psoriasis as a disease model to study how chronic inflammation effects myocardial perfusion, measured by myocardial flow reserve (MFR) on positron emission tomography (PET) and cardiac MRI (CMR), and myocardial function and tissue composition measured by multi-modality cardiovascular imaging.

Objectives:

To test the hypothesis that chronic inflammation is a driver of perturbances in myocardial perfusion, function, and tissue composition
To test the hypothesis that biologic treatment for psoriasis will be associated with longitudinal improvement in myocardial perfusion, function, and tissue composition
To characterize immune cell subsets and their association with myocardial perfusion, function, and tissue composition in chronic inflammation
To explore how chronic inflammation may alter myocardial energetics and metabolism

Endpoints:

Primary outcomes will be:

Myocardial perfusion, as assessed by myocardial flow reserve (MFR), in subjects with moderate to severe psoriasis compared to matched healthy controls.

Secondary outcomes will be:

Change in MFR in subjects with psoriasis on biologic therapy at 1 year follow-up compared to baseline.

Diastolic function (on echocardiogram), myocardial mechanics (on echocardiogram and CMR), myocardial edema and inflammation, and interstitial fibrosis (on CMR) in subjects with moderate to severe psoriasis compared to matched healthy controls.

Change in diastolic function, myocardial mechanics, myocardial edema and inflammation, and interstitial fibrosis in subjects with psoriasis on biologic therapy at 1 year follow- up

Exploratory outcomes will be:

Immune cell subsets by flow cytometry in subjects with 7 moderate to severe psoriasis compared to matched healthy controls

Rest and stress left ventricular oxygen consumption (MVO2) in subjects with moderate to severe psoriasis compared to matched healthy controls

Study Design

Study Type:

Observational

Anticipated Enrollment :

168 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

The Effect of Chronic Inflammation on Myocardial Perfusion and Function

Actual Study Start Date :

Jun 7, 2021

Anticipated Primary Completion Date :

Jun 30, 2024

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Affected Subjects Subjects diagnosed with moderate- severe psoriasis
Healthy Controls Females and males 18 years of age or older

Outcome Measures

Primary Outcome Measures

Miocardial perfusion in affected vs healthy individuals [1 day]
Primary outcome will be: Myocardial perfusion, as assessed by myocardial flow reserve (MFR), in subjects with moderate to severe psoriasis compared to matched healthy controls.

Secondary Outcome Measures

Change in MFR in subjects on biologic therapy [1 year]
Change in MFR in subjects with psoriasis on biologic therapy at 1 year follow-up compared to baseline. 2.Diastolic function (on echocardiogram), myocardial mechanics (on echocardiogram and CMR), myocardial edema and inflammation, and interstitial fibrosis (on CMR) in subjects with moderate to severe psoriasis compared to matched healthy controls. 3.Change in diastolic function, myocardial mechanics, myocardial edema and inflammation, and interstitial fibrosis in subjects with psoriasis on biologic therapy at 1 year follow- up

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

INCLUSION CRITERIA:

Subjects of both genders will be considered for inclusion in this study. There will be no racial, ethnic, or gender discrimination.

Affected Subjects:

18 years of age or older
Diagnosed with moderate-severe psoriasis clinically confirmed by a licensed physician, or advanced practitioner consisting of typical skin findings and/or associated findings of systemic disease of joints, nails, and hair and may be scheduled to initiate biologic

treatment for psoriasis

Healthy Controls:

Females and males 18 years of age or older

EXCLUSION CRITERIA:

Affected Subjects:

Pregnant or lactating women
Subjects with a contraindication to MRI scanning will not receive the CMR assessment.

These contraindications include subjects with the following devices:

Central nervous system aneurysm clips
Implanted neural stimulator
Implanted cardiac pacemaker or defibrillator
Cochlear implant
Ocular foreign body (e.g. metal shavings)
Implanted Insulin pump
Metal shrapnel or bullet
Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m^2 body surface area according to the Modification of Diet in Renal Disease criteria

History of seizures or taking anti-epileptic medications
Inability to provide informed consent

Healthy Controls:

Diagnosis of inflammatory disease (including psoriasis, psoriatic arthritis, rheumatoid arthritis, lupus, inflammatory bowel disease)
Pregnant women and lactating women
Subjects with a contraindication to MRI scanning will not receive the CMR assessment.

These contraindications include subjects with the following devices:

Central nervous system aneurysm clips
Implanted neural stimulator
Implanted cardiac pacemaker or defibrillator
Cochlear implant
Ocular foreign body (e.g. metal shavings)
Implanted Insulin pump
Metal shrapnel or bullet
Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m^2 body surface area according to the Modification of Diet in Renal Disease criteria