The Effect of SGLT2 Inhibition on Adipose Inflammation and Endothelial Function

NCT05972564 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 210907 (SADIE2)
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

Obesity is associated with increased cardiometabolic disease risk due, in part, to heightened chronic inflammation arising from adipose tissue. There are no current targeted therapies to prevent or reverse the chronic inflammation of obesity, and a better understanding of these inflammatory pathways in humans is key to future therapeutic interventions. This trial will determine both the anti-inflammatory potential of the SGLT2 inhibitor empagliflozin, and the contribution of adipose inflammation to surrogate measures of cardiovascular disease in a randomized controlled trial of obese patients.

Conditions

Obesity; Metabolic Syndrome

Outcome Measures

Primary Outcomes (3)

• Adipose tissue macrophages

  Homeostatic adipose tissue macrophages are quantified

  12 weeks

• Flow mediated dilation

  Brachial artery diameter is measured under basal conditions and during reactive hyperemia

  12 weeks

• Monocyte chemoattractant protein-1

  Plasma monocyte chemoattractant protein-1 levels are quantified

  12 weeks

Secondary Outcomes (2)

• Pro-inflammatory T cells

  12 weeks

• IL-6

  12 weeks

Study Arms (2)

Empagliflozin Arm

ACTIVE COMPARATOR

Empagliflozin is an FDA-approved SGLT2 inhibitor used for the treatment of type 2 diabetes, with off-label use for diabetic kidney disease and for heart failure with reduced ejection fraction even in those without diabetes. To ensure blinding, empagliflozin will be over-encapsulated in identical gelatin capsules as placebo.

Drug: Empagliflozin 25 MG

Placebo Arm

PLACEBO COMPARATOR

Placebo consists of gelatin capsules.

Drug: Placebo

Interventions

Empagliflozin 25 MG DRUG

Empagliflozin is an FDA-approved SGLT2 inhibitor used for the treatment of type 2 diabetes, with off-label use for diabetic kidney disease and for heart failure with reduced ejection fraction even in those without diabetes.

Also known as: Jardiance

Empagliflozin Arm

Placebo DRUG

Placebo consists of gelatin capsules.

Placebo Arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 70 years old
• Metabolic syndrome as defined by 3 or more of 5 criteria:
• Systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 85 mmg Hg or treatment with anti-hypertensive medications for minimum of 1 month
• Triglycerides ≥ 150 mg/dL or treatment with a triglyceride-targeted medication (fenofibrate, gemfibrozil, niacin, high dose omega-3 fatty acids)
• High-density lipoprotein (HDL) \< 40 mg/dL in males or \< 50 mg/dL in females
• Fasting blood glucose ≥ 100mg/dL or treatment with glucose-lowering medications
• Waist circumference ≥ 102 cm in males or ≥ 88cm in females
• BMI ≥ 35 kg/M2
• Scheduled gastric bypass or gastric sleeve in approximately 90 days (range 90-270 days)
• The ability to provide informed consent

You may not qualify if:

• Type 1 diabetes.
• Poorly controlled type 2 diabetes as defined by HbA1c ≥ 9%.
• Use of anti-diabetic medications other than stable dose of metformin or a sulfonylurea in the last 1 month.
• Treatment with a glucagon-like peptide-1 receptor agonist or co-agonist in the last 3 months.
• Treatment with an SGLT2 inhibitor in the last 3 months.
• Pregnancy or breast-feeding. Women of child-bearing potential will be required to have undergone surgical sterilization or to be using an intra-uterine device, hormonal contraceptive, or barrier methods of birth control.
• Cardiovascular disease such as myocardial infarction within six months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (left ventricular hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, -second- or third-degree heart block, mitral valve stenosis, aortic stenosis, or hypertrophic cardiomyopathy
• Presence of implanted cardiac defibrillator or pacemaker
• History of serious neurologic disease such as cerebral hemorrhage, stroke, or transient ischemic attack
• History of pancreatitis or pancreatic surgery
• History or presence of immunological or hematological disorders
• Clinically significant gastrointestinal impairment that could interfere with drug absorption
• History of advanced liver disease with cirrhosis
• Individuals with an eGFR\<45 mL/min/1.73 m2, where eGFR is determined by the four-variable Modification of Diet in Renal Disease (MDRD) equation, where serum creatinine is expressed in mg/dL and age in years: eGFR (mL/min/1.73m2)=186 • Scr-1.154 • age-0.203 • (0.742 if female)
• Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month)

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

MeSH Terms

Conditions

Obesity; Metabolic Syndrome

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Study Officials

• Mona Mashayekhi, MD, PhD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mona Mashayekhi, MD, PhD

CONTACT

615-208-5037; mona.mashayekhi@vumc.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo consists of gelatin capsules. To ensure blinding, empagliflozin will be over-encapsulated in identical gelatin capsules as placebo.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Division of Diabetes, Endocrinology and Metabolism

Model Details: Participants will be randomized to placebo or empagliflozin in a 1:1 ratio, stratified for race and sex. A study biostatistician will prepare the randomization and allocation schedule.

Study Record Dates

• First Submitted: July 24, 2023
• First Posted: August 2, 2023
• Study Start: September 6, 2023
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: June 13, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)