Effects of Empagliflozin on Endogenous Glucose Production in End Stage Renal Disease(ESRD).

A Phase II,Randomized,Cross-over,Double-blind, Placebo- Controlled,Single Center Study of the Effect of Empagliflozin a SGLT-2 Inhibitor,on Endogenous Glucose Production and Plasma Glucagon Levels in Patients With ESRD

A study of the effects of empagliflozin, a SGLT-2 inhibitor, on endogenous glucose production and plasma glucagon levels in patients with end-stage renal disease (ESRD)

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease
• Intervention / Treatment: Combination product: Empagliflozin; Drug: Placebo

Detailed Description

The impact of SGLT-2 inhibition on endogenous glucose production and plasma glucagon levels will be compared measured in patients with ESRD.The secondary endpoints are the mean difference in plasma glucose, insulin, c-peptide, FFA,GH, epinephrine, norepinephrine, cortisol and blood pressure during the last hour of the experiment between empagliflozin versus placebo administration in patients.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Pisa, Italy, 56124
    • Department of Endocrinology and Metabolism, University of Pisa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males and females
2. Age = 30-70 years
3. BMI< 40 Kg/m 2 and stable weight (± 3 lbs) over the preceding three months
4. Normal Glucose Tolerance (HbA1c > 4.5 % and < 5.7%) or Type 2 diabetes (HbA1c >5.7 % and <10.0%)
5. End Stage Renal Disease (GFR <15 ml/min/1.73 m 2 or hemodialysis)
6. Subjects are capable of giving informed consent

Exclusion Criteria:

1. Prednisone treatment
2. Beta blocker or any medication that affects sympathetic/parasympathetic activity
3. Known Empagliflozin Excipient Hypersensitivity
4. Liver function enzymes higher more than two times the upper limit
5. Ongoing urinary tract infection
6. history of cancer of any type;
7. cerebrovascular or symptomatic peripheral vascular disease;
8. heart disease class III or IV NYHA;
9. Type 1 Diabetes
10. drug or alcohol abuse;
11. life expectancy <3 yrs
12. blood pressure >150/100 mmHg
13. Donation of blood to a blood bank, blood transfusion, or participation in a clinical study requiring withdrawal of > 400 mL of blood during the 8 weeks prior to the enrollment visit and at least 8 weeks thereafter
14. Women of child bearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study (estrogen and/or progesterone treatment)
15. Patient with a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance which, in the opinion of the investigator or coordinator, might pose an unacceptable risk to the patient or interfere with trial procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Empagliflozin; SGLT-2 inhibitor	Combination product: Empagliflozin; Sodium-glucose co-transporter 2 (SGLT2), a low-affinity, high-capacity member of an increasingly numerous family of co-transporters, is highly expressed in the proximal renal tubule, and account for the majority of the reabsorption of filtered glucose.
Placebo Comparator: placebo; A substance without specific pharmacology principles.	Combination product: Empagliflozin; Sodium-glucose co-transporter 2 (SGLT2), a low-affinity, high-capacity member of an increasingly numerous family of co-transporters, is highly expressed in the proximal renal tubule, and account for the majority of the reabsorption of filtered glucose.; Drug: Placebo; A substance without specific pharmacology principles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in plasma Glucose level	Because of their mechanism of action, SGLT-2 inhibitor efficacy to reduce plasma glucose level is highly dependent upon renal function. With GFR decreasing, glucose tubular load will decrease and less glucose will be reabsorbed because of SGLT2-inhibition.	2 hours

Collaborators and Investigators

• Sponsor: University of Pisa
• Investigators: Principal Investigator: Stefano Del prato, University of Pisa

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2018
• Primary Completion (Actual): February 15, 2020
• Study Completion (Actual): March 15, 2020

Study Registration Dates

• First Submitted: July 18, 2018
• First Submitted That Met QC Criteria: October 18, 2018
• First Posted (Actual): October 19, 2018

Study Record Updates

• Last Update Posted (Actual): September 14, 2021
• Last Update Submitted That Met QC Criteria: September 13, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: EMPA-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No