SGLT2 Inhibitor Effects on Inflammation and Heart Disease in Obesity Pilot

NCT04907214 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 210907
• Study Type: interventional
• Target: 29
• 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 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.

Conditions

Obesity; Pre-diabetes

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (2)

• Change in Adipose Pro-inflammatory T Helper Type 1 Cell Percentages After 2 Weeks

  Baseline to 2 weeks

• Change in the Plasma Inflammatory Cytokine IL-6 After 3 Months

  Baseline to 12 weeks

Study Arms (1)

Empagliflozin

EXPERIMENTAL

Individuals receive empagliflozin 25mg/day orally for 12 weeks

Drug: Empagliflozin 25 MG

Interventions

Empagliflozin 25 MG DRUG

Oral empagliflozin daily

Empagliflozin

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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Obesity; Glucose Intolerance

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Mona Mashayekhi
• Organization: Vanderbilt University Medical Center

mona.mashayekhi@vumc.org

615-936-1760

Study Officials

• Mona Mashayekhi, MD/PhD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Instructor

Study Record Dates

• First Submitted: May 25, 2021
• First Posted: May 28, 2021
• Study Start: July 29, 2021
• Primary Completion: December 8, 2023
• Study Completion: December 8, 2023
• Last Updated: December 29, 2023
• Results First Posted: February 1, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)