SGLT2 Inhibitor Effects on Inflammation and Heart Disease in Obesity Pilot
Study Details
Study Description
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 project 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Empagliflozin Individuals receive empagliflozin 25mg/day orally for 12 weeks |
Drug: Empagliflozin 25 MG
Oral empagliflozin daily
|
Outcome Measures
Primary Outcome Measures
- Change in adipose pro-inflammatory T cell numbers after 3 months [Baseline to 12 weeks]
Pro-inflammatory T cells are quantified using flow cytometry
Secondary Outcome Measures
- Change in adipose pro-inflammatory T cell numbers after 2 weeks [Baseline to 2 weeks]
Pro-inflammatory T cells are quantified using flow cytometry
- Change in plasma inflammatory cytokines after 3 months [Baseline to 12 weeks]
Pro-inflammatory cytokines in plasma are quantified, including interferon-gamma, tumor necrosis factor-alpha, and interleukin-6.
- Change in endothelium-dependent vasodilation as measured by Flow-mediated dilation after 3 months [Baseline to 12 weeks]
To assess endothelium-dependent vasodilation, brachial artery diameter is measured under basal conditions and during reactive hyperemia.
Eligibility Criteria
Criteria
Inclusion criteria:
-
Age 18 to 70 years old
-
Impaired glucose tolerance (two-hour plasma glucose 140-199 mg/dL) or impaired fasting glucose (100-125mg/dL) or HbA1c 5.7-6.4%
-
BMI ≥ 30 kg/M2
-
The ability to provide informed consent
Exclusion criteria:
Criteria Related to Medical Diagnoses/Conditions/Treatments:
-
Diabetes type 1 or type 2, as defined by a fasting plasma glucose of 126 mg/dL or greater, a two-hour plasma glucose of 200 mg/dL or greater, HbA1c ≥6.5%, or the use of anti-diabetic medication
-
Pregnancy or breast-feeding. Women of child-bearing potential will be required to have undergone tubal ligation or to be using an oral 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)
-
Treatment with anticoagulants
-
Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult
-
History of alcohol abuse (>14 per week for men and >7 per week for women) or illicit drug use
-
Treatment with any investigational drug in the one month preceding the study
-
Previous randomization in this trial
-
Mental conditions rendering a subject unable to understand the nature, scope and possible consequences of the study
-
Inability to comply with the protocol in the opinion of the principal investigator, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
Criteria Related to Known Adverse Effects of Drug:
-
Uncircumcised men or men with history of balanitis
-
History of urinary incontinence
-
History of recurrent (>3) episodes of vulvovaginitis per year, or severe symptoms
-
History of Fournier's gangrene
-
History of recurrent (≥3) UTIs per year or pyelonephritis
-
History of symptomatic hypotension or conditions predisposing to volume depletion
-
Known peripheral vascular disease, neuropathy, history of foot ulcers or lower limb amputations
-
Treatment with loop diuretics furosemide, torsemide, bumetanide, ethacrynic acid
-
Known or suspected allergy to trial medications, excipients, or related products
-
Contraindications to study medications, worded specifically as stated in the product's prescribing information
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Vanderbilt University Medical Center | Nashville | Tennessee | United States | 37232 |
Sponsors and Collaborators
- Vanderbilt University Medical Center
Investigators
- Principal Investigator: Mona Mashayekhi, MD/PhD, Vanderbilt University Medical Center
Study Documents (Full-Text)
More Information
Publications
None provided.- 210907