PROTOCOL 3: Role of the Renal Nerves in the Increase in EGP in Response to Glucosuria

SGLT2 INHIBITION AND STIMULATIION OF ENDOGENOUS GLUCOSE PRODUCTION Significance - PROTOCOL 3: Role of the Renal Nerves in the Increase in EGP in Response to Glucosuria

Sponsors

Lead Sponsor: The University of Texas Health Science Center at San Antonio

Collaborator: National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Source The University of Texas Health Science Center at San Antonio
Brief Summary

Purpose/Objectives: Examining the effect of SGLT2 inhibition on EGP and plasma glucose concentration in diabetic and non-diabetic subjects after kidney transplantation (i.e. renal denervation) or in subjects after renal sympathectomy (63) can add insight about the possible role of a neural arc which mediates the changes in plasma glucagon and/or insulin concentration in response to glucosuria.

Detailed Description

Purpose/Objectives: Examining the effect of SGLT2 inhibition on EGP and plasma glucose concentration in diabetic and non-diabetic subjects after kidney transplantation (i.e. renal denervation) or in subjects after renal sympathectomy (63) can add insight about the possible role of a neural arc which mediates the changes in plasma glucagon and/or insulin concentration in response to glucosuria.

Research Design/Plan: After screening, eligible subjects will receive 2 measurements of endogenous glucose production with a prime-continuous infusion of 3-3H-glucose. Each measurement will be performed on a separate day in random order after a 10-12 hour overnight fast and will last 8 hours (from 6 AM to 2 PM). After a 3-hour tracer equilibration period, each subject will receive one of the following medications in random order: (i) placebo and (ii) dapagliflozin 10 mg. Following the test medication at 9 AM, blood samples will be drawn every 20 minutes for an additional 5 hours and plasma glucose, insulin, C-peptide, glucagon, catecholamine concentrations and tritiated glucose sp act will be measured.

Methods: Visit 1: Screening Visit 2: Endogenous Glucose Production Measurement (EGP) Visit 3: After completing the first EGP measurement, subjects will return to the Diabetes Research Unit for the second study.

Overall Status Completed
Start Date October 2016
Completion Date May 15, 2019
Primary Completion Date October 2018
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
Change in Endogenous Glucose Production (EGP) baseline and 240-300 minutes
Secondary Outcome
Measure Time Frame
Change in Fasting Plasma Glucose baseline and 240-300 minutes
Change in Fasting Plasma Insulin baseline and 240-300 minutes
Enrollment 34
Condition
Intervention

Intervention Type: Drug

Intervention Name: Dapagliflozin 10mg then Placebo Oral Tablet

Description: SGLT2 inhibitor - Dapagliflozin then Placebo

Other Name: Farxiga then placebo

Intervention Type: Drug

Intervention Name: Placebo Oral Tablet then Dapagliflozin 10mg

Description: Placebo then SGLT2 inhibitor - Dapagliflozin

Other Name: Placebo then Farxiga

Eligibility

Criteria:

Inclusion Criteria:

- age = 18-70 years

- BMI = 18.5-40 kg/m2

- HbA1c ≥ 7.0% and ≤10.0% for type 2 diabetics

- males or females

- Must be at least 3 months post renal transplantation and be on a stable dose of prednisone (≤5 mg/day), tacrolimus, and mycophenolate mofetil

- Not taking any antidiabetic medications or who are treated with metformin, sulfonylurea, dipeptidyl peptidase 4 (DPP4) inhibitor, thiazolidinedione or some combination

- Must be in good general health as determined by physical exam, medical history, blood chemistries, CBC, TSH, T4, EKG and urinanalysis

Exclusion Criteria:

- Subjects who are taking insulin or SGLT2 inhibitor are excluded

- Only subjects whose body weight has not been stable (± 3 lbs) over the preceding three months and/or who participate in an excessively heavy exercise program will be excluded.

- Individuals with evidence of proliferative diabetic retinopathy, plasma creatinine >1.4 females or >1.5 males (and eGFR <45ml/min.1.73m2), or 24-hour urine albumin excretion > 300 mg will be excluded.

Gender: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Ralph A DeFronzo, MD Principal Investigator The University of Texas Health Science at San Antonio
Location
Facility: The University of Texas Health Science Center at San Antonio
Location Countries

United States

Verification Date

December 2019

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Label: Placebo first and then dapagliflozin

Type: Experimental

Description: Renal transplant subjects with intact native kidneys with Type 2 Diabetes Mellitus receive dapagliflozin then placebo

Label: Dapagliflozin first then placebo

Type: Active Comparator

Description: Renal transplant subjects with intact native kidneys who are non-diabetic receive placebo then dapagliflozin

Label: Control Group

Type: Other

Description: Subjects who are type 2 diabetes mellitus who have not undergone renal transplant.

Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Crossover Assignment

Intervention Model Description: Post renal transplant type 2 diabetes mellitus patients and non-diabetic mellitus patients after renal transplant with a control group of type 2 diabetes mellitus who have not undergone renal transplant

Primary Purpose: Basic Science

Masking: None (Open Label)

Source: ClinicalTrials.gov