Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Can Exenatide Prevent the Increase in EGP in Response to Dapagliflozin-induced Increase in Glucosuria

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.
ClinicalTrials.gov Identifier: NCT03331289
Recruitment Status : Recruiting
First Posted : November 6, 2017
Last Update Posted : April 1, 2019
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Ralph DeFronzo, The University of Texas Health Science Center at San Antonio

Tracking Information
First Submitted Date  ICMJE October 31, 2017
First Posted Date  ICMJE November 6, 2017
Last Update Posted Date April 1, 2019
Actual Study Start Date  ICMJE February 28, 2018
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 31, 2017)
  • Change in EGP [ Time Frame: 240-300 minutes ]
    The difference in rate of EGP during the last hour of the study (from 240-300 minutes) between drug-treatment and placebo treatment studies represents the effect of drug treatment on EGP, which will be compared among the 3 drug treatments (exenatide; dapagliflozin; exenatide plus dapagliflozin) with ANOVA.
  • change in EGP above baseline following dapagliflozin alone versus dapagliflozin/exenatide [ Time Frame: -35 - 0 minutes ]
    The following primary comparison will be performed: (i) change in EGP above baseline following dapagliflozin alone versus dapagliflozin/exenatide.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03331289 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Can Exenatide Prevent the Increase in EGP in Response to Dapagliflozin-induced Increase in Glucosuria
Official Title  ICMJE SGLT2 INHIBITION AND STIMULATION OF ENDOGENOUS GLUCOSE PRODUCTION Significance : Protocol- 4 Can the GLP-1 Receptor Agonist, Exenatide, Prevent the Increase in EGP in Response to Dapagliflozin-induced Increase in Glucosuria
Brief Summary

Research Design/Plan: After screening, each subject will receive 1 measurements of EGP with prime-continuous Infusion of 3-3H-glucose. After completing the EGP measurement each subject will receive a Double Tracer OGTT.

Methods: Visit 1: Screening. Medical history will be obtained, physical exam performed, and pregnancy test performed.

Visit 2: Endogenous Glucose Production Measurement: The rate of EGP will be measured with 3-3H-glucose.

Visit 3: Double Tracer OGTT

Detailed Description

Eligible subjects will receive a measurement of endogenous glucose production (EGP) with a prime-continuous infusion of 3-3H-glucose. The EGP measurement will be performed in the morning 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, subjects (20 per group) will receive one of the following medications: (i) placebo; (ii) exenatide 5 ug subcutaneously; (iii) dapagliflozin (10 mg); and (iv) dapagliflozin 10 mg plus exenatide 5 ug. Following the test medication at 9 AM, blood samples will be drawn every 15 minutes for an additional 5 hours and plasma glucose, insulin, C-peptide, glucagon, cortisol, growth hormone, and catecholamine concentrations and glucose specific activity will be measured.

Visit 1: Screening. Medical history & physical exam will be performed. Blood will be drawn for FPG, routine blood chemistries, CBC, lipid profile, HbA1c, and thyroid function. Urinalysis, EKG, albumin/creatinine ratio and pregnancy test will be performed.

Visit 2: EPG Measurement: The rate of endogenous glucose production will be measured with 3-3H-glucose infusion. [3-3H]-glucose infusion will be started at 6 AM and continued until 2:30 PM (5 hours after drug administration). At 6 AM a catheter will be placed into an anticubital vein and a prime (40 uCi x FPG/100)- continuous (0.4 uCi) infusion of [3-3H]- glucose will be started and continued until 2:30 PM. (5 hours after drug administration). Participant's hand will be placed in a box heated to 50-60°C (122-140°F). Baseline blood samples will be obtained at-210, -60, -50, -45, -40, -35, -30, -20, -10, and 0 . After 3.5 hours of tracer equilibration blood samples will be obtained every 10-20 minutes from 9 AM to 2 PM. Plasma glucose, insulin, C-peptide, glucagon, cortisol, growth hormone, and catecholamine concentrations, and [3-3H]-glucose specific activity will be measured. Urine will be collected from 6 to 9 AM and from 9 AM to 2 PM. Urinary volume and glucose concentration will be measured and urinary glucose excretion rate calculated. The study will end at 2:30 PM.

Visit 3: Double Tracer Oral Glucose Tolerance Test: Within the week after the measurement of EGP, all subjects will have a 5-hour OGTT with measurement of plasma glucose, insulin (I), C-peptide (CP), and glucagon concentrations at -180, -6-, -5-, -45, -40, -35, -30, -20, -10, 0 and every 15-30 minutes thereafter to obtain a measure of overall glucose tolerance, insulin secretion (CP0-120/G0-120), insulin sensitivity ([MI]), beta cell function, (CP0-120/G0-120 x MI), and suppression of plasma glucagon concentration (64). At 7 AM a catheter will be placed into an anticubital vein and a prime (25 uCi x FPG/100)- continuous (0.25 uCi) infusion of [3-3H]- glucose will be started and continued until 3 PM. Urinary volume and glucose concentration will be measured and urinary glucose excretion rate calculated.

HbA1c will be measured 2x, 1 on the day of the OGTT & 1 on the day of the EGP measurement.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:
Participants will be randomized to one of four groups (20 per group): i) placebo; (ii) exenatide 5 ug subcutaneously; (iii) dapagliflozin (10 mg); and (iv) dapagliflozin 10 mg plus exenatide 5 ug
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Diabetes Mellitus, Type 2
Intervention  ICMJE
  • Drug: Placebo
    Placebo will be administered to 20 subjects after a 3 hour tracer equilibration period
  • Drug: Exenatide
    Exenatide will be administered to 20 subjects after a 3 hour tracer equilibration period
    Other Name: Byetta, Bydureon
  • Drug: Dapagliflozin
    Dapagliflozin will be administered to 20 subjects after a 3 hour tracer equilibration period
    Other Name: Farxiga
  • Drug: Exenatide and Dapagliflozin
    Exenatide and Dapagliflozin will be administered to 20 subjects after a 3 hour tracer equilibration period
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    we will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose conc compared to each agent alone.
    Intervention: Drug: Placebo
  • Active Comparator: Exenatide
    we will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose conc compared to each agent alone.
    Intervention: Drug: Exenatide
  • Active Comparator: Dapagliflozin
    we will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose conc compared to each agent alone.
    Intervention: Drug: Dapagliflozin
  • Active Comparator: Exenatide and Dapagliflozin
    we will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose conc compared to each agent alone.
    Intervention: Drug: Exenatide and Dapagliflozin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 31, 2017)
80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Health Status: Type 2 Diabetes Mellitus according to ADA criteria (subjects must be in good general health as determined by physical exam, medical history, blood chemistry-CBC, TSH, T4, EKG and urinalysis)
  • BMI: 21-45kg/m
  • HbA1C>7.0% and <10.0%
  • Medication: Drug naïve and/or on a stable dose of metformin and/or sulfonylurea (more than 3 months)

Exclusion Criteria:

  • Health Status: Type 1 Diabetics
  • Proliferative diabetic retinopathy
  • Plasma Creatinine greater than 1.4mg/dL in females or greater than 1.5mg/dL in males, or 24 hour urine albumin excretion greater than 300mg/dL
  • Medication: Subjects taking drugs known to affect glucose metabolism (other than metformin and sulfonylurea)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Ralph DeFronzo, MD 210-567-6691 defronzo@uthscsa.edu
Contact: Eugenio Cersosimo, MD PhD 210-358-7200 cersosimo@uthsca.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03331289
Other Study ID Numbers  ICMJE HSC20170582H
R01DK107680 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Ralph DeFronzo, The University of Texas Health Science Center at San Antonio
Study Sponsor  ICMJE Ralph DeFronzo
Collaborators  ICMJE National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators  ICMJE Not Provided
PRS Account The University of Texas Health Science Center at San Antonio
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP