NCT05330013

The Effect of Inflammation in Heart Failure

Pilot Study to Evaluate the Effect of Inflammation in Heart Failure

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: National Heart, Lung, and Blood Institute (NHLBI) · NIH
• Sex: All
• Age: 18 Years – 90 Years
• Healthy volunteers: Accepted

Summary

Background: Heart failure is a serious health condition. Researchers believe inflammation plays a role. They want to see if adding an additional heart drug to a person s treatment can help treat heart failure with preserved ejection fraction (HFpEF). Objective: To learn if chronic inflammation is high in heart failure and if taking dapagliflozin along with the standard of care medicines for 6 months will reduce inflammation and improve heart function in people with HFpEF. Eligibility: People aged 18 and older who have heart failure and qualify for dapagliflozin therapy. Healthy adult volunteers are also needed. Design: * Participants will be screened with: * Medical history * Physical exam * Heart function tests * X-ray scans of the heart and blood vessels. They may receive medicines to slow their heart rate or make their heart blood vessels bigger. An intravenous (IV) catheter will be placed in their arm to inject contrast. * Blood and urine tests * Participants will have up to 3 study visits. Some screening tests will be repeated. Participants will take one tablet of the study drug daily for 6 months. -Participants will have an imaging scan of their heart and blood vessels. They will receive a contrast and stress medicine through an IV to view blood supply. Participants will have a stress test that measures exercise ability. They will wear sticky pads on their chest, a blood pressure cuff, and a mask. They will also have a 6-Minute Walk Test. Participants will complete questionnaires about their symptoms and their health. Participants may be on the study for up to 6 months. They will have a follow-up phone call 1 month after treatment ends. ...

Detailed description

Study Description: Heart failure (HF) remains a significant public health burden. Unlike heart failure with reduced ejection fraction (HFrEF), heart failure with preserved ejection fraction (HFpEF) currently does not have any effective therapies, suggesting incomplete understanding of the underlying mechanisms of the syndrome. Chronic inflammation has been postulated to be one of the central mechanisms in HFpEF pathogenesis. In this pilot study to be conducted at the NIH Clinical Center, we propose to examine the role of the NLRP3 inflammasome- IL-1 pathway in HFpEF and evaluate whether treatment using the sodium glucose co-transport 2 (SGLT2) inhibitor dapagliflozin can attenuate NLRP3 inflammasome activation. Objectives: * To test the hypothesis that macrophage NLRP3 inflammasomeactivation is upregulated in subjects with HFpEF compared to healthy controls and that NLRP3 inflammasome activation will be attenuated by dapagliflozin therapy * To test the hypothesis that pro-inflammatory signatures in peripheral blood mononuclear cells (PBMCs) will be increased in HFpEF compared to healthy controls and that they will be attenuated by dapagliflozin therapy * To test the hypothesis that macrophage NLRP3 inflammasome activation associates with perturbances in myocardial perfusion, structure, and function and that attenuation of NLRP3 inflammasome activation with dapagliflozin therapy will associate with improvement in myocardial perfusion, myocardial structure, and function * To test the hypothesis that NLRP3 inflammasome activation is inversely associated with maximum oxygen consumption (VO2max), exercise functional status, and symptoms in HFpEF and that attenuation of NLRP3 inflammasome activation with dapagliflozin therapy will associate with improvement in VO2max, exercise functional status, and symptoms. Endpoints: Primary outcome will be: -IL-1 beta, a measure of NLRP3 inflammasome activation, from macrophages in subjects with HFpEF compared to healthy controls. Secondary outcomes will be: * Delineation of the differences in PBMC gene expression profiles measured by RNA sequencing and in immunophenotyping signatures measured by flow cytometry in subjects with HFpEF compared to healthy controls. The effect of dapagliflozin on these immunological profiles will also be determined in the HFpEF study subjects. * Myocardial perfusion (on CMR), left ventricular mass (on CMR), diastolic function (on echocardiogram), myocardial mechanics (on echocardiogram and CMR), myocardial edema and inflammation, and interstitial fibrosis (on CMR) in subjects with HFpEF compared to healthy controls and in response to dapagliflozin therapy. Exploratory outcomes will be: \- VO2max, symptoms and exercise functional status in HFpEF compared to healthy controls and in response to dapagliflozin therapy.

Conditions

• Myocardial Dysfunction
• Heart Failure
• Inflammation

Interventions

Type	Name	Description
DRUG	Dapagliflozin	Subjects will be instructed to take dapagliflozin 10 mg once daily for 6 months (with or without food).
DEVICE	MRI scan	For subjects, depending on the subject's heart rate, base, mild, or apex short-axis slices will be acquired during the first pass of the contract (60 measurements).
DEVICE	CMR imaging	Enrolled subjects will undergo stress vasodilator and rest perfusion CMR

Timeline

• Start date: 2022-06-23
• Primary completion: 2022-06-23
• Completion: 2022-06-23
• First posted: 2022-04-15
• Last updated: 2022-06-27

Locations

1 site across 1 country: United States