Clinical trial NCT04907214: SGLT2 Inhibitor Effects on Inflammation and Heart Disease in Obesity Pilot
Official title: The Effect of SGLT2 Inhibition on Adipose Tissue Inflammation and Endothelial Function Pilot
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Obesity
Pre-diabetes
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2021-05-28
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

Detailed description: This study will be expanded to include another 10 participants. Enrollment will begin July 1, 2023.

Eligibility criteria: Inclusion criteria:

1. Age 18 to 70 years old
2. Impaired glucose tolerance (two-hour plasma glucose 140-199 mg/dL) or impaired fasting glucose (100-125mg/dL) or HbA1c 5.7-6.4%
3. BMI ≥ 30 kg/M2
4. The ability to provide informed consent

Exclusion criteria:

Criteria Related to Medical Diagnoses/Conditions/Treatments:

1. 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
2. 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
3. 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
4. Presence of implanted cardiac defibrillator or pacemaker
5. History of serious neurologic disease such as cerebral hemorrhage, stroke, or transient ischemic attack
6. History of pancreatitis or pancreatic surgery
7. History or presence of immunological or hematological disorders
8. Clinically significant gastrointestinal impairment that could interfere with drug absorption
9. History of advanced liver disease with cirrhosis
10. 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)
11. Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month)
12. Treatment with anticoagulants
13. 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
14. History of alcohol abuse (\>14 per week for men and \>7 per week for women) or illicit drug use
15. Treatment with any investigational drug in the one month preceding the study
16. Previous randomization in this trial
17. Mental conditions rendering a subject unable to understand the nature, scope and possible consequences of the study
18. 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:
19. Uncircumcised men or men with history of balanitis
20. History of urinary incontinence
21. History of recurrent (\>3) episodes of vulvovaginitis per year, or severe symptoms
22. History of Fournier's gangrene
23. History of recurrent (≥3) UTIs per year or pyelonephritis
24. History of symptomatic hypotension or conditions predisposing to volume depletion
25. Known peripheral vascular disease, neuropathy, history of foot ulcers or lower limb amputations
26. Treatment with loop diuretics furosemide, torsemide, bumetanide, ethacrynic acid
27. Known or suspected allergy to trial medications, excipients, or related products
28. Contraindications to study medications, worded specifically as stated in the product's prescribing information

Primary outcomes:
measure: Change in Adipose Pro-inflammatory T Helper Type 1 Cell Percentages After 3 Months
timeFrame: Baseline to 12 weeks
measure: Change in Flow-mediated Dilation After 3 Months
timeFrame: Baseline to 12 weeks
measure: Change in Liver Steatosis at 3 Months
timeFrame: Baseline to 12 weeks
Secondary outcomes:
measure: Change in Adipose Pro-inflammatory T Helper Type 1 Cell Percentages After 2 Weeks
timeFrame: Baseline to 2 weeks
measure: Change in the Plasma Inflammatory Cytokine IL-6 After 3 Months
timeFrame: Baseline to 12 weeks
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Mona Mashayekhi, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References: