Early Metabolic Adaptations to SGLT2 Inhibition in Heart Failure

NCT05885607 | Enrolling By Invitation

• 1 other identifier: 853146
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Heart Failure NYHA Class II; Heart Failure NYHA Class III; Heart Failure

Outcome Measures

Primary Outcomes (1)

• 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.

  4-8 weeks

Secondary Outcomes (3)

• Assess the impact of SGLT21 on ambulation

  4-8 weeks

• Assess the impact of SGLT2i on skeletal muscle oxidative phosphorylation capacity (SkM OxPhos)

  4-8 weeks

• Assess the impact of SGLT2i on skeletal muscle perfusion during exercise

  4-8 weeks

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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
• 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)##

Sponsors & Collaborators

• University of Pennsylvania: lead
• Amgen: collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Biomarkers * 20 mL of Blood Plasma K2EDTA * 20 mL of Blood Serum

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Kenneth Margulies, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: May 10, 2023
• First Posted: June 2, 2023
• Study Start: June 27, 2023
• Primary Completion: February 9, 2026
• Study Completion: March 31, 2026
• Last Updated: February 13, 2026

Record last verified: 2025-08

Locations

US (1)