The Effect of Inflammation in Heart Failure

NCT05330013 | Withdrawn Phase 2

• 2 other identifiers: 10000710000710-H
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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. ...

Conditions

Myocardial Dysfunction; Heart Failure; Inflammation

Keywords

Dapagliflozin; Hfpef; Cardiac MRI; NLRP3 Inflammasome; Perfusion

Outcome Measures

Primary Outcomes (1)

• IL-1 beta levels

  IL-1 beta, a measure of NLRP3 inflammasome activation, from macrophages in subjects with HFpEF compared to healthy controls

  6 months

Secondary Outcomes (2)

• Change in CMR, ECHO in affected vs healthy individuals

  2.5 years

• Immunological profiles in affected vs healthy individuals

  2.5 years

Study Arms (2)

Control

OTHER

Healthy volunteers who are age and sex matched

Device: MRI scan; Device: CMR imaging

Subjects with HFpEF

EXPERIMENTAL

Subjects are defined as patients with a diagnosis of HFpEF clinically confirmed by a licensed physician or advanced practitioner who meet the inclusion and exclusion criteria and are able to provide informed consent.

Drug: Dapagliflozin; Device: MRI scan; Device: CMR imaging

Interventions

Dapagliflozin DRUG

Subjects will be instructed to take dapagliflozin 10 mg once daily for 6 months (with or without food).

Subjects with HFpEF

MRI scan DEVICE

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).

Control; Subjects with HFpEF

CMR imaging DEVICE

Enrolled subjects will undergo stress vasodilator and rest perfusion CMR

Control; Subjects with HFpEF

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Affected Subjects:
• years of age or older
• Diagnosed with HFpEF clinically confirmed by licensed physician or advanced practitioner
• Signs and symptoms of HFpEF
• LVEF \>= 50% on echocardiography from screening visit
• Left ventricular hypertrophy (interventricular septal thickness (Bullet) 1cm) or enlarged left atrial volume ( (Bullet)34ml/m2) on echocardiography from screening visit
• NT-proBNP \> 300pg/mL
• Healthy Controls:
• Females and males 18 years of age or older

You may not qualify if:

• Affected Subjects:
• Pregnant or lactating women
• Acute coronary syndrome, cardiac surgery or percutaneous coronary intervention within past 6 months
• Atrial fibrillation
• Coronary artery disease with \>= 50% stenosis in the left main, left anterior descending artery, left circumflex artery, or right coronary artery on CCTA from screening visit
• Infiltrative cardiomyopathy by diagnosis or imaging
• \> Moderate valvular stenosis on screening echocardiography
• Diagnosis of an inflammatory disease (including psoriasis, psoriatic arthritis, rheumatoid arthritis, lupus, inflammatory bowel disease, HIV)
• Currently taking an SGLT2 inhibitor
• Estimated glomerular filtration rate (eGFR) \< 45 mL/min/1.73m\^2 body surface area according to the Modification of Diet in Renal Disease criteria
• Subjects with a contraindication to MRI scanning will not receive the CMR assessment.
• These contraindications include subjects with the following devices:
• i. Central nervous system aneurysm clips
• ii. Implanted neural stimulator
• iii. Implanted cardiac pacemaker or defibrillator

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Kim SR, Lee SG, Kim SH, Kim JH, Choi E, Cho W, Rim JH, Hwang I, Lee CJ, Lee M, Oh CM, Jeon JY, Gee HY, Kim JH, Lee BW, Kang ES, Cha BS, Lee MS, Yu JW, Cho JW, Kim JS, Lee YH. SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease. Nat Commun. 2020 May 1;11(1):2127. doi: 10.1038/s41467-020-15983-6.

  PMID: 32358544 BACKGROUND

• Brown AJM, Gandy S, McCrimmon R, Houston JG, Struthers AD, Lang CC. A randomized controlled trial of dapagliflozin on left ventricular hypertrophy in people with type two diabetes: the DAPA-LVH trial. Eur Heart J. 2020 Sep 21;41(36):3421-3432. doi: 10.1093/eurheartj/ehaa419.

  PMID: 32578850 BACKGROUND

• Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Bohm M, Brunner-La Rocca HP, Choi DJ, Chopra V, Chuquiure-Valenzuela E, Giannetti N, Gomez-Mesa JE, Janssens S, Januzzi JL, Gonzalez-Juanatey JR, Merkely B, Nicholls SJ, Perrone SV, Pina IL, Ponikowski P, Senni M, Sim D, Spinar J, Squire I, Taddei S, Tsutsui H, Verma S, Vinereanu D, Zhang J, Carson P, Lam CSP, Marx N, Zeller C, Sattar N, Jamal W, Schnaidt S, Schnee JM, Brueckmann M, Pocock SJ, Zannad F, Packer M; EMPEROR-Preserved Trial Investigators. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021 Oct 14;385(16):1451-1461. doi: 10.1056/NEJMoa2107038. Epub 2021 Aug 27.

  PMID: 34449189 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Heart Failure; Inflammation

Interventions

dapagliflozin; Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Wunan Y Zhou, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2022
• First Posted: April 15, 2022
• Study Start: June 23, 2022
• Primary Completion: June 23, 2022
• Study Completion: June 23, 2022
• Last Updated: June 27, 2022

Record last verified: 2022-06

Locations

US (1)