Heart Failure Clinical Trial
Early Metabolic Adaptations to SGLT2 Inhibition in Heart Failure
Summary
The goal of this observational study is to learn about SGLT2 inhibition medications in patients with symptomatic heart failure who are clinically prescribed FDA-approved SGLT2 inhibitors. The main question it aims to answer is:
What are the impacts of SGLT2 inhibition on systemic metabolomic and proteomic profiles? Participants will be asked to do the following before and after being prescribed a SGLT2i.
Six-minute walk testd
Calf MRI with plantar flexion exercise
Blood sample collection
Full Description
Schema
Total anticipated enrollment: 40 participants This is an observational study in patients being initiated on an FDA-approved SGLT2i treatment for symptomatic HF (on-label use). This observational study involves supplemental research testing before and after SGLT2i initiation to help define how the treatment affects the body.
Study Design
This will be a single-center study that will characterize early changes in systemic metabolic and proteomic profiles, skeletal muscle oxidative capacity and six-minute walk distance before and after initiation of SGLT2i treatment. The paired study design will specifically target patients with symptomatic heart failure whose physicians are prescribing FDA-approved SGLT2i treatment. Pre- vs. post-treatment profiling will be performed during the first 4-8 weeks of therapy. Eligibility is not limited to a particular range of LVEF or affected by prior LVEF.
Visit Procedures
Visit 1: Enrollment/Baseline Visit
Eligibility/Informed Consent
Medical History, Medications Review
Visit 2: Pre-SGLT2i Testing
Blood sample collection
Six-minute walk test
Calf MRI with plantar flexion exercise
Visit 3: Post-SGLT2i Testing
Blood sample collection
Six-minute walk test
Calf MRI with plantar flexion exercise
Study Objectives
Primary
- Assess the impact of SGLT2i on systemic metabolomic and proteomic profiles
Secondary
Assess the impact of SGLT21 on ambulation
Assess the impact of SGLT2i on skeletal muscle oxidative phosphorylation capacity (SkM OxPhos)
Assess the impact of SGLT2i on skeletal muscle perfusion during exercise
Study Endpoints
We will measure changes in venous concentrations of metabolic substrates and intermediates, along with circulating proteomic regulators using both targeted and untargeted surveys.
Differences in distance traveled during a standardized 6 minute walk test.
OxPhos as assessed using CrCEST MRI spectroscopy
MRI-based assessment of SkM Perfusion: Differences in conduit artery blood flow and intramuscular perfusion using vPIVOT MRI imaging
Risks and Benefits Overview
As an observational study, the risks of this research are confined to those associated with the supplemental testing that is being performed: blood sampling, six-minute walk testing and MRI scanning with foot flexion exercise. Blood sampling and six-minute walk testing have minimal risk. After eliminating individuals with absolute contraindications to MRI scanning, such as retained metal fragments or implanted devices that are not MRI compatible, risks related to this MRI study are limited and include feeling uncomfortable in the MRI scanner and developing minor leg discomfort from the one-foot exercise required. Individuals with implanted pacemakers or defibrillators designated as "MRI-conditional" may be included. Subjects who are not eligible for MRI studies may still participate in the blood sampling and six-minute walk test assessments
Eligibility Criteria
Inclusion Criteria:
Age ≥18 years
Clinically diagnosed HF documented in the patient's medical record
NYHA Class II-III functional status, according to the most recent clinical evaluation
Availability of an echocardiogram or cardiac MRI within the prior year
Stable HF medical therapy (no change in beta-blocker, ACE/ARB, ARNI or MRA for at least 4 weeks prior to screening) with the exception of diuretics
Planned initiation of on-label SGLT2i therapy
Exclusion Criteria:
Receiving therapy with an SGLT2 inhibitor within 8 weeks prior to enrollment or previous intolerance to an SGLT2 inhibitor
Subject inability/unwillingness to perform a six-minute walk test
Acute coronary syndrome or unstable angina within the past month
Previous cardiac transplantation or implantation of a ventricular assist device
Any condition that will interfere with the completion of the study. This may include comorbid conditions or logistical factors that may impede successful completion of the protocol (e.g. inability to travel for follow-up visits)
Absolute Exclusions for the Leg MRI Assessment (may still participate in blood sampling and six-minute walk testing):
ANY intracranial implants of any type other than dental fillings
ANY non-removable piercings, jewelry, or medicinal patch
ANY personal history of intraocular injury or fragment in or around the orbit that cannot be cleared through radiologic examination
ANY personal history of bullet, shrapnel, or stabbing wounds that cannot be cleared through radiologic evaluation.
ANY non-removable life assist device, pump, or prosthetic
Possible Exclusions** for the Leg MRI Assessment (may still participate in blood sampling and six-minute walk testing):
An intra-luminal implant, filter, stent, or valve replacement
A vascular clip or clamp
A surgically placed clip, clamp or band on visceral organs
A cardiac pacemaker or implanted cardiac defibrillator (ICD)##
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There is 1 Location for this study
Philadelphia Pennsylvania, 19104, United States
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