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

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03168295
• Other study ID #: HSC20160042H
• Secondary ID: R01DK107680
• Status: Completed
• Phase: Phase 4
• Start date: October 2016
• Est. completion date: May 15, 2019

Study information

• Verified date: September 2020
• Source: The University of Texas Health Science Center at San Antonio
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: May 15, 2019
• Est. primary completion date: October 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2

Intervention

Drug:
• Dapagliflozin 10mg then Placebo Oral Tablet
SGLT2 inhibitor - Dapagliflozin then Placebo
• Placebo Oral Tablet then Dapagliflozin 10mg
Placebo then SGLT2 inhibitor - Dapagliflozin

Locations

Country	Name	City	State
United States	The University of Texas Health Science Center at San Antonio	San Antonio	Texas

Sponsors (3)

Lead Sponsor	Collaborator
The University of Texas Health Science Center at San Antonio	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Endogenous Glucose Production (EGP)	Renal transplant subjects with native kidneys intact underwent measurement of EGP with an 8 hour infusion of 3-3H-glucose on 2 separate days with the administration in random order of either dapagliflozin 10mg or placebo after 3 hours of the tracer equilibration period. The equilibration at 3 hours was considered the baseline measurement. Measurement of change in endogenous glucose production was obtained for all subjects.	baseline and 240-300 minutes
Secondary	Change in Fasting Plasma Glucose	Change in Fasting Plasma Glucose in Type 2 Diabetes Mellitus subjects only	baseline and 240-300 minutes
Secondary	Change in Fasting Plasma Insulin	Change in Fasting Plasma Insulin in Type 2 Diabetes Mellitus subjects in diabetic subjects only	baseline and 240-300 minutes