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Effect of Dapagliflozin on Hepatic and Renal Glucose Metabolism Subjects

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ClinicalTrials.gov Identifier: NCT02981966
Recruitment Status : Recruiting
First Posted : December 5, 2016
Last Update Posted : June 12, 2019
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Eugenio Cersosimo, The University of Texas Health Science Center at San Antonio

Brief Summary:
Researchers hope to determine the organ (liver and/or kidney) responsible for the increase in endogenous glucose production (EGP) following the induction of glucosuria (when glucose is excreted in detectable amounts in the urine) with an SGLT2 inhibitor, dapagliflozin.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Drug: Dapagliflozin Drug: Placebo Phase 4

Detailed Description:
Researchers will measure the rate of hepatic and renal glucose production following dapagliflozin administration to determine the site of increase in EGP, liver versus kidney. Researchers will measure the rate of whole body glucose production with 3-3H-glucose (a form of radioactive glucose) and renal glucose production by renal vein catheterization in T2DM (type 2 diabetes mellitus) and in lean healthy NGT (normal glucose tolerance) individuals. Because the increase in EGP is associated with an increase in plasma glucagon concentration and renal glucose production is stated to be unresponsive to glucagon, the investigators anticipate that the liver will be responsible, in part, for the increase in EGP.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effect of Dapagliflozin on Hepatic and Renal Glucose Metabolism Subjects (11038)
Actual Study Start Date : May 23, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Normal Glucose Tolerance (NGT)
Individuals with normal glucose tolerance - dapagliflozin vs placebo
Drug: Dapagliflozin
dapagliflozin, 10mg tablet
Other Name: Farxiga

Drug: Placebo
Placebo for dapagliflozin

Active Comparator: T2DM individuals
Individuals with type 2 diabetes mellitus - dapagliflozin vs placebo
Drug: Dapagliflozin
dapagliflozin, 10mg tablet
Other Name: Farxiga

Drug: Placebo
Placebo for dapagliflozin




Primary Outcome Measures :
  1. Endogenous Glucose Production NGT subjects - dapa [ Time Frame: 3 weeks ]
    Endogenous Glucose Production NGT subjects after dapagliflozin administration

  2. Endogenous Glucose Production NGT subjects - placebo [ Time Frame: 3 weeks ]
    Endogenous Glucose Production NGT subjects after placebo administration

  3. Endogenous Glucose Production T2DM subjects - dapa [ Time Frame: 3 weeks ]
    Endogenous Glucose Production T2DM subjects after dapagliflozin administration

  4. Endogenous Glucose Production T2DM subjects - placebo [ Time Frame: 3 weeks ]
    Endogenous Glucose Production T2DM subjects after placebo administration


Secondary Outcome Measures :
  1. Renal Glucose Production NGT subjects - dapa [ Time Frame: 3 weeks ]
    Renal Glucose Production NGT subjects after dapagliflozin administration

  2. Renal Glucose Production NGT subjects - placebo [ Time Frame: 3 weeks ]
    Renal Glucose Production NGT subjects after placebo administration

  3. Renal Glucose Production T2DM subjects - dapa [ Time Frame: 3 weeks ]
    Renal Glucose Production T2DM subjects after dapagliflozin administration

  4. Renal Glucose Production T2DM subjects - placebo [ Time Frame: 3 weeks ]
    Renal Glucose Production T2DM subjects after placebo adminsitration



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 25-35 kg/m^2
  • Normal Glucose Tolerance subjects (24)
  • Type 2 Diabetic Subjects (24)
  • Diabetic subjects must be on a stable dose (more than 3 months) of monotherapy or combination therapy with metformin and/or a sulfonylurea
  • Diabetic subjects must have HbA1c <8.0%
  • Other than diabetes, subjects must be in good general health as determined by physical exam, medical history, blood chemistries, CBC (complete blood count), TSH (thyroid-stimulating hormone), T4 (thyroxine), EKG (electrocardiogram) and urinanalysis.
  • Only subjects whose body weight has been stable (± 3 lbs) over the preceding three months and who do not participate in an excessively heavy exercise program will be included.

Exclusion Criteria:

  • Subjects taking drugs known to affect glucose metabolism (other than metformin and sulfonylurea) will be excluded.
  • Individuals with evidence of proliferative diabetic retinopathy, plasma creatinine >1.4 females or >1.5 males, or 24-hour urine albumin excretion > 300 mg will be excluded.

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 ClinicalTrials.gov identifier (NCT number): NCT02981966


Contacts
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Contact: Eugenio Cersosimo, MD, PhD 210-358-7200 cersosimo@uthscsa.edu
Contact: Ralph DeFronzo, MD 210-567-6691 defronzo@uthscsa.edu

Locations
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United States, Texas
University of Texas Health Science Center Recruiting
San Antonio, Texas, United States, 78229
Contact: Eugenio Cersosimo, MD    210-358-7200    cersosimo@uthscsa.edu   
Contact: Ralph A DeFronzo, MD    210-567-6691    defronzo@uthscsa.edu   
Principal Investigator: Eugenio Cersosimo, MD, PhD         
Sponsors and Collaborators
The University of Texas Health Science Center at San Antonio
AstraZeneca
Investigators
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Principal Investigator: Eugenio Cersosimo, MD,PhD The University of Texas Health Science Center at San Antonio

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Responsible Party: Eugenio Cersosimo, Associate Professor, The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT02981966     History of Changes
Other Study ID Numbers: HSC20160596H
First Posted: December 5, 2016    Key Record Dates
Last Update Posted: June 12, 2019
Last Verified: June 2019
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
Additional relevant MeSH terms:
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Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs