SGLT2 Inhibitor Effects on Inflammation and Heart Disease in Obesity Pilot

Obesity Clinical Trial

Official title:

The Effect of SGLT2 Inhibition on Adipose Tissue Inflammation and Endothelial Function Pilot

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04907214
• Other study ID #: 210907
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 29, 2021
• Est. completion date: December 8, 2023

Study information

• Verified date: December 2023
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: December 8, 2023
• Est. primary completion date: December 8, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Inflammation
• Obesity
• Pre-diabetes
• Prediabetic State

Intervention

Drug:
• Empagliflozin 25 MG
Oral empagliflozin daily

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Adipose Pro-inflammatory T Helper Type 1 Cell Percentages After 3 Months	Pro-inflammatory T helper type 1 cells are quantified using flow cytometry	Baseline to 12 weeks
Primary	Change in Flow-mediated Dilation After 3 Months	Endothelial function quantified using flow-mediated dilation by ultrasound, measuring percentage increase in artery diameter during hyperemia.	Baseline to 12 weeks
Primary	Change in Liver Steatosis at 3 Months	Liver steatosis assessment by transient elastography-controlled attenuation parameter imaging, reported as Controlled Attenuation Parameter (CAP)	Baseline to 12 weeks
Secondary	Change in Adipose Pro-inflammatory T Helper Type 1 Cell Percentages After 2 Weeks	Pro-inflammatory T cells are quantified using flow cytometry	Baseline to 2 weeks
Secondary	Change in the Plasma Inflammatory Cytokine IL-6 After 3 Months	IL-6 is quantified in plasma samples.	Baseline to 12 weeks