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

Study Overview
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Brief Summary
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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)

Detailed Description
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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.

Official Title
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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

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Combination Product: Empagliflozin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females Age = 30-70 years BMI&lt; 40 Kg/m 2 and stable weight (± 3 lbs) over the preceding three months Normal Glucose Tolerance (HbA1c &gt; 4.5 % and &lt; 5.7%) or Type 2 diabetes (HbA1c &gt;5.7 % and &lt;10.0%) End Stage Renal Disease (GFR &lt;15 ml/min/1.73 m 2 or hemodialysis) Subjects are capable of giving informed consent Exclusion Criteria: Prednisone treatment Beta blocker or any medication that affects sympathetic/parasympathetic activity Known Empagliflozin Excipient Hypersensitivity Liver function enzymes higher more than two times the upper limit Ongoing urinary tract infection history of cancer of any type; cerebrovascular or symptomatic peripheral vascular disease; heart disease class III or IV NYHA; Type 1 Diabetes drug or alcohol abuse; life expectancy &lt;3 yrs blood pressure &gt;150/100 mmHg Donation of blood to a blood bank, blood transfusion, or participation in a clinical study requiring withdrawal of &gt; 400 mL of blood during the 8 weeks prior to the enrollment visit and at least 8 weeks thereafter 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) 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

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Empagliflozin<br>SGLT-2 inhibitor | Combination Product: Empagliflozin<br>* 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.<br>|
| Placebo Comparator: placebo<br>A substance without specific pharmacology principles. | Combination Product: Empagliflozin<br>* 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.<br>Drug: Placebo<br>* A substance without specific pharmacology principles<br>|

What is the study measuring?
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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 |