Heart Failure NYHA Class IIEMAS-HFNCT05885607
Early Metabolic Adaptations to SGLT2 Inhibition in Heart Failure
An observational study of Heart Failure NYHA Class II and Heart Failure NYHA Class III, run by University of Pennsylvania at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure NYHA Class II, Heart Failure NYHA Class III, Heart Failure
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Jun 2023to 30 Jun 2027
- How long will I take part?
- 1 Year
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: This study will be performed in approximately 40 outpatient participants with symptomatic heart failure (HF) who are being started on SGLT2i treatment by their provider.
Who may be able to join
- 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
Who cannot join
- 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):
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- 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)##
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
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
Read the detailed 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
- Medical subject headings
- Heart Failure
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess the impact of SGLT2i on systemic metabolomic and proteomic profiles
We will measure changes in venous concentrations of metabolic substrates and intermediates, along with circulating proteomic regulators using both targeted and untargeted surveys. SGLT2i has been shown to impact glucose, fatty acid, and ketone metabolism.
Measured: 4-8 weeks
Secondary outcomes (3)
Assess the impact of SGLT21 on ambulation
Differences in distance traveled during a standardized 6-minute walk test. Changes in systemic or skeletal muscle metabolism may improve walking distance.
Measured: 4-8 weeks
Assess the impact of SGLT2i on skeletal muscle oxidative phosphorylation capacity (SkM OxPhos)
OxPhos as assessed using CrCEST MRI spectroscopy. SkM OxPhos is a major topic of interest for this proposal. We hypothesize that SGLT2i may improve skeletal muscle OxPhos.
Measured: 4-8 weeks
Assess the impact of SGLT2i on skeletal muscle perfusion during exercise
MRI-based assessment of SkM Perfusion: Differences in conduit artery blood flow and intramuscular perfusion using vPIVOT MRI imaging. Changes in dynamic responses of SkM blood flow may be a contributor to the improvements in exercise tolerance we hypothesize will occur with SGLT2i
Measured: 4-8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2023
- Study start27 Jun 2023
- Primary completion28 Feb 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure NYHA Class IIStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
- Target duration
- 1 Year
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Principal investigator, Kenneth B Margulies, University of Pennsylvania
- Investigators
- Kenneth Margulies, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05885607
- Sponsor's protocol ID
- 853146
- Acronym
- EMAS-HF
- Status last verified
- May 2026
- First submitted
- 10 May 2023
- Last updated
- 4 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No