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Dapagliflozin and Hepatic Glucose Metabolism

Sponsor
The University of Texas Health Science Center at San Antonio (Other)
Overall Status
Recruiting
CT.gov ID
NCT03193684
Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
108
Enrollment
1
Location
2
Arms
66.4
Anticipated Duration (Months)
1.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease Intervention/Treatment Phase
Phase 4

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
108 participants
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 treatmentsubjects 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
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
Primary Purpose:
Basic Science
Official Title:
Effect of Dapagliflozin on Hepatic Glucose Metabolism: Role of Autonomic Nervous System
Actual Study Start Date :
May 20, 2018
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Dec 1, 2023

Arms and Interventions

Arm Intervention/Treatment
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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. effect of dapagliflozin on autonomic nervous system [12 weeks]

      autonomic activity will be measured with as NE turnover rate

    Secondary Outcome Measures

    1. hepatic glucose production and uptake [12 weeks]

      HGP and HGU will be measured with tracer dilution technique

    Other Outcome Measures

    1. hepatic fat content [12 weeks]

      the effect of treatment on hepatic fat content will be measured with MRS

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Diabetes Division, UTHSCSA San Antonio Texas United States 78229

    Sponsors and Collaborators

    • The University of Texas Health Science Center at San Antonio
    • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

    Investigators

    • Principal Investigator: Muhammad Abdul-Ghani, MD, PhD, Diabetes Division, UTHSCSA

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    The University of Texas Health Science Center at San Antonio
    ClinicalTrials.gov Identifier:
    NCT03193684
    Other Study ID Numbers:
    • HSC20170214H
    • 2R01DK097554-06
    First Posted:
    Jun 21, 2017
    Last Update Posted:
    Jul 5, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Additional relevant MeSH terms:
    Dapagliflozin

    Study Results

    No Results Posted as of Jul 5, 2022