Purpose

the aim of this study is to examine the role of autonomic nervous system in the increase in hepatic glucose production in response to glucosuria caused by inhibition of renal glucose uptake

Condition

Eligibility

Eligible Ages
Between 18 Years and 65 Years
Eligible Genders
All
Accepts Healthy Volunteers
Yes

Inclusion Criteria

  • eGFR>60 ml/min healthy volunteers type 2 diabetes patients who otherwise healthy

Exclusion Criteria

  • eGFR <60 T2DM patients on insulin, GLP-1 RA or SGLT2 treatment Major organ disease type 1 diabetes

Study Design

Phase
Phase 4
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
subjects will receive in parallel a treatment with dapagliflozin or placebo for 3 months hepatic glucose metabolism and norepinephrine turnover will be studied before and after treatment
Primary Purpose
Basic Science
Masking
Double (Participant, Investigator)
Masking Description
the study is placebo controlled double blinded. randomization will be made by pharmacist and the randomization code will be kept in the pharmacy

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Treatment
dapagliflozin 10 mg per day
  • Drug: Dapagliflozin 10mg
    subjects will receive daily dose of 10 mg dapagliflozin for 3 months
Placebo Comparator
control
matching placebo 1 pill per day
  • Drug: Control
    Placebo
    Other names:
    • Placebo

Recruiting Locations

Diabetes Division, UTHSCSA
San Antonio, Texas 78229
Contact:
Andrea Hansis-Diarte, MPH
210-617-5300
HansisDiarte@uthscsa.edu

More Details

Status
Recruiting
Sponsor
The University of Texas Health Science Center at San Antonio

Study Contact

Muhammad Abdul-Ghai, MD, PhD
210 567 6691
ABDULGHANI@UTHSCSA.EDU

Detailed Description

Purpose/Objectives: To investigate the effect of dapagliflozin, an SGLT2 inhibitor on hepatic glucose production and the role of autonomic nervous system in mediating the increase in hepatic glucose production in response glucosuria Research Design/Plan: the role of autonomic nervous system in the increase in hepatic glucose production caused by dapagliflozin will be examined with norepinephrine (NE) turnover in two protocols. The first protocol is cross sectional, in which 36 T2DM patients will receive hepatic glucose production (HGP) and NE turnover will be measured before and after dapagliflozin or placebo administration. In protocol 2, diabetic and non-diabetic subjects will receive baseline HGP, NE turnover, hepatic glucose uptake (HGU) and liver fat measurement before at 2 days after the start and 12 weeks after dapagliflozin or placebo treatment.

Methods: the following techniques will be employed (1) Measurement of hepatic glucose production with 3H-glucose infusion, with and without glucose clamp, (2) substrate oxidation with indirect calorimetry and plasma ketone/lactate/insulin/glucagon concentrations; (3) Measurement of HGU with Oral-IV double tracer infusion; (4) Measurement of whole body norepinephrine turnover with 3H-norepinephrine infusion; (5) Measurement of heart rate variability; (6) Measurement of liver fat content with 1H-MRS Clinical Relevance: The results of the present studies will help identify the mechanism responsible for the increase in HGP caused by dapagliflozin and the increase in ketone production. The first action of the drug ameliorates its clinical efficacy while the second increases the risk of adverse events (ketoacidosis). Identifying the mechanisms underlying these actions will help developing therapeutic strategies which increase the drug clinical efficacy and mitigates its adverse events.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.