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Trial record 1 of 1 for:    NCT03193684
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Dapagliflozin and Hepatic Glucose Metabolism

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03193684
Recruitment Status : Recruiting
First Posted : June 21, 2017
Last Update Posted : June 5, 2020
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
The University of Texas Health Science Center at San Antonio

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
Hepatic Glucose Metabolism Drug: Dapagliflozin 10mg Drug: Control 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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 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
Estimated Primary Completion Date : January 31, 2022
Estimated Study Completion Date : January 31, 2023

Resource links provided by the National Library of Medicine

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
Other Name: Placebo

Primary Outcome Measures :
  1. effect of dapagliflozin on autonomic nervous system [ Time Frame: 12 weeks ]
    autonomic activity will be measured with as NE turnover rate

Secondary Outcome Measures :
  1. hepatic glucose production and uptake [ Time Frame: 12 weeks ]
    HGP and HGU will be measured with tracer dilution technique

Other Outcome Measures:
  1. hepatic fat content [ Time Frame: 12 weeks ]
    the effect of treatment on hepatic fat content will be measured with MRS

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03193684

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Contact: Muhammad Abdul-Ghai, MD, PhD 210 567 6691 ABDULGHANI@UTHSCSA.EDU
Contact: MONICA PALOMO, BSc 210 567 6710

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United States, Texas
Diabetes Division, UTHSCSA Recruiting
San Antonio, Texas, United States, 78229
Contact: Andrea Hansis-Diarte, MPH    210-617-5300 ext 17822   
Sponsors and Collaborators
The University of Texas Health Science Center at San Antonio
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Principal Investigator: Muhammad Abdul-Ghani, MD, PhD Diabetes Division, UTHSCSA
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Responsible Party: The University of Texas Health Science Center at San Antonio Identifier: NCT03193684    
Other Study ID Numbers: HSC20170214H
2R01DK097554-06 ( U.S. NIH Grant/Contract )
First Posted: June 21, 2017    Key Record Dates
Last Update Posted: June 5, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs