Diagnostic Utility of SGLT1/2 Inhibition to Facilitate Myocardial Glucose Suppression

January 6, 2026 updated by: Paco Bravo, MD, University of Pennsylvania

Diagnostic Utility of SGLT1/2 Inhibition to Facilitate Myocardial Glucose Suppression During Evaluation of Cardiac Inflammation on FDG-PET

This is a pilot mechanistic study of the diagnostic utility of sodium-glucose cotransporter-1/2 inhibition (SGLT1/2) on myocardial glucose suppression on FDG PET/CT. The investigators will test whether the addition of a SGLT1/2 inhibitor (SGLT1/2i) plus the standard dietary modification (ketogenic diet) will provide enhanced myocardial glucose suppression. The primary objective is to assess rates of complete myocardial glucose suppression (MGS) with 7 days of sotagliflozin 400 mg QD among healthy volunteers on a background of 1 day (N=20) or 3 days (N=20) of the KD. The secondary goal is to investigate the relationship between sotagliflozin, targeted metabolite levels, and myocardial glucose utilization on FDG-PET.

Participants will be asked to:

  • undergo a screening visit that includes blood tests, vitals, and questions regarding health history/medications
  • take the provided sotagliflozin as instructed for 7 days leading up to the scan
  • follow a ketogenic diet as instructed for 1 or 3 days leading up to the scan
  • undergo an FDG PET/CT scan, which includes vitals and blood draws

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The purpose of this mechanistic pilot study is to evaluate the effect on myocardial glucose suppression, and therefore on image quality, with the addition of a brief course of an FDA approved SGLT1/2 inhibitor prior to FDG PET/CT scan. FDG PET/CT is a clinically utilized scan for diagnosis of cardiac sarcoidosis following the standard diet and fasting requirements, this study will test the addition of the 7 days of sotagliflozin prior to the scan.

Sotagliflozin (INPEFA™) is a sodium-glucose cotransporter-2 inhibitor (SGLT1/2i) Sodium-glucose cotransporter-2 inhibitor that has been studied in humans and is FDA approved for reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors. In this study, the investigators will be using it "off-label" in healthy volunteers and will be using only a short course (approximately 1 week) of the drug prior to the FDG PET/CT PET scan. "Off-label" use is when an FDA approved drug is prescribed for a condition/use other than that for which the drug has been officially approved. Therefore, the study will be utilizing sotagliflozin in way that it has yet to be approved for by the FDA.

The investigators may enroll up to 40 fully evaluable healthy volunteers. A fully evaluable subject must complete the PET/CT scan. Subjects who do not complete the PET/CT scan will not be counted as fully evaluable, however, collected data may still be used in some secondary analyses. The participants will be aged at least 18 years old. After completing a screening visit and meeting study eligibility, each participant will undergo an FDG PET scan after taking sotagliflozin for 7 (up to 10 maximum) days and following a ketogenic diet for either 1 day (N=20) prior to the scan with overnight fasting or 3 days (N=20) prior to the scan with overnight fasting. Enrollment of the 20 participants undergoing 3 days of KD is dependent on sufficient funding, and therefore initial efforts will be targeted toward enrolling participants in the 1 day of KD stratum. Participants will be asked to track when they have taken the sotagliflozin in a provided diary.

FDG PET/CT imaging will be used to evaluate glycolytic activity in the heart using the FDA approved clinical Positron Emission Tomography (PET) radiotracer, [18F] Fluorodeoxyglucose (FDG) Imaging will be done on a dedicated whole-body PET scanner. For each PET scan, dynamic images over the body will be acquired from the time of injection to up to 60 minutes after injection of FDG. Imaging data will be processed as per standard protocols. The study will be performed under the regulatory approval of the Penn Institutional Review Board (IRB).

Participants will undergo an FDG PET/CT after taking 7 (up to 10 maximum) days of oral sotagliflozin overlapping with 1 or 3 day(s) of dietary modification (standard ketogenic diet) and overnight fasting prior to FDG injection.

For all subjects, the investigators may measure blood levels of BHB, lipids, basic metabolic panel, complete blood counts HbA1c, free fatty acid, acylcarnitine, glucose, and insulin at screening, some of these tests will be repeated on the day of the scan. The investigators plan to use the Penn Metabolomics Core and Penn Diabetes Radioimmunoassay and Biomarkers Core for sample processing. Since intravenous access will be obtained for administration of the tracer on the day of the PET scan, a blood draw will be performed from this line. Thereafter, the investigators will perform comprehensive, targeted metabolomic profiling from this peripheral blood so the study team can correlate myocardial suppression with other metabolic markers. Most of the research testing will occur at later dates with stored samples. The lab test results that may be entered in the medical record include BHB, lipids, basic metabolic panel, complete blood counts and glucose. Other experimental test results will not be provided to the subjects.

Participants will be asked to follow a standard prescribed ketogenic diet and keep a diet diary during the KD prior to the FDG PET visit, this diet matches the clinical SOC pre-scan preparation for sarcoidosis. On the day of FDG-PET, the diet diary will be collected and reviewed by an investigator. The diet will also be reviewed, usually at a later date, by a CHPS nutritional specialist and information reported by the subject will be used to perform meal analysis and estimate grams of fat, protein and carbohydrates.

This is a single institution, pilot mechanistic study of FDG PET/CT to determine optimal method of myocardial glucose suppression. Patients may participate in this study if they are greater than 18 years of age. Subjects that may meet eligibility criteria will be approached about study participation regardless of race or ethnic background.

Study Type

Observational

Enrollment (Estimated)

40

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

40 evaluable healthy volunteers

Description

Inclusion Criteria:

  1. Adult patients, at least 18 years of age
  2. No history of cardiovascular disease, including hypertension, hyperlipidemia, diabetes mellitus, heart failure, coronary artery disease, cardiac surgery, arrhythmias per medical record review and/or self-report
  3. No history of chronic liver or kidney disease per medical record review and/or self-report.
  4. Participants must be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study-specific procedures.

Exclusion Criteria:

  1. Females who are pregnant or breast-feeding will not be eligible for this study. Female participants of child-bearing potential will have a urine pregnancy test during the screening visit and prior to FDG injection.
  2. Participants who are currently taking diuretics for any indication.
  3. Participants with an eGFR level <30 mL/min/1.73m2.
  4. Inability to tolerate imaging procedures in the opinion of the investigator or treating physician.
  5. Any other medical or psychological condition that, in the opinion of the investigator would compromise the subject's safety or successful participation in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Ketogenic Diet with sotagliflozin
40 volunteers will take a SGLT1/2i, sotagliflozin (400 mg QD), for 7 days prior to the PET scan visit and will undergo FDG PET/CT after 1-3 day of dietary modification (ketogenic diet for at least 3-9 meals) and overnight fasting prior to FDG injection.
Drug: Sotagliflozin
Sodium-glucose cotransporter-1/2 inhibitor
Other Names:
  • INPEFA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete myocardial glucose suppression
Time Frame: 7 days
Rate of complete myocardial glucose suppression after 7-day regimen of sotagliflozin
7 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Myocardial glucose utilization
Time Frame: 7 days
Myocardial glucose utilization in FDG PET/CT measured by SUV in the heart
7 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pennsylvania

Collaborators

Duke University

Investigators

  • Principal Investigator: Paco Bravo, MD, University of Pennsylvania

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 20, 2024

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

July 15, 2024

First Submitted That Met QC Criteria

July 15, 2024

First Posted (Actual)

July 19, 2024

Study Record Updates

Last Update Posted (Actual)

January 7, 2026

Last Update Submitted That Met QC Criteria

January 6, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 855451

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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