ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Dapagliflozin on Mitochondrial Dysfunction and Impaired Insulin Signaling/Action (DAPA MITO)

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. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01439854
Recruitment Status : Completed
First Posted : September 23, 2011
Last Update Posted : July 10, 2018
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

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
The purpose of this study is to examine the effect of the chronic treatment of type 2 diabetes (T2DM) with dapagliflozin on: (1) mitochondrial gene function/expression and insulin signaling/action and (2) oral glucose tolerance and beta cell function. Dapagliflozin is a potent, highly specific inhibitor of renal glucose transport [SGLT2].

Condition or disease Intervention/treatment Phase
Insulin Sensitivity Multiple Mitochondrial Dysfunctions Syndrome Drug: Dapagliflozin Drug: Placebo Not Applicable

Detailed Description:
"Glucotoxicity" has been implicated as a cause of insulin resistance and impaired beta cell function in T2DM. Abundant support for the glucotoxicity hypothesis has been provided by in vivo and in vitro studies in animals, but a rigorous test of this hypothesis in man is lacking. The investigators propose to test the glucotoxicity hypothesis by chronically reducing the plasma glucose in type 2 diabetic subjects (T2DM) with an inhibitor of renal glucose transport, dapaglifozin, and examining the effect of restoration of normoglycemia on mitochondrial function and insulin signaling/sensitivity. Lastly, the investigators will test the "glucolipotoxicity" hypothesis, which states that the toxic effects of elevated plasma FFA on insulin sensitive tissues (i.e., muscle) are magnified in the presence of concurrent hyperglycemia. Thus, high glucose levels increase malonyl CoA, which inhibits CPT I, leading to accumulation of FACoA/DAG, which impair mitochondrial function and inhibit insulin action.

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 66 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Regulation of Hepatic and Peripheral Glucose Metabolism: Protocol IVA. Effect of Plasma Glucose Reduction by Selective SLGT2 Inhibition on Mitochondrial Dysfunction and Impaired Insulin Signaling/Sensitivity in T2DM
Study Start Date : March 2011
Actual Primary Completion Date : June 30, 2018
Actual Study Completion Date : June 30, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Allergy

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Placebo Comparator: Placebo
this arm is control
 Drug: Placebo
Patients are treated with placebo
Experimental: Dapagliflozin
Interventional arm
 Drug: Dapagliflozin
Treatment arm, 10 mg per day for 2 weeks


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Change in Insulin Sensitivity [ Time Frame: baseline, two weeks ]
    The change in insulin sensitivity and total glucose disposal measured at two weeks with the insulin clamp compared to baseline.


Secondary Outcome Measures :
  1. Change in Mitochondrial Function [ Time Frame: baseline, two weeks ]
    The change in mitochondrial function/gene expression at two weeks compared to baseline.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • T2DM
  • Drug Naive Or On Oral Therapy

Exclusion Criteria:

  • Insulin Treatment
  • Major Organ Disease
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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): NCT01439854


Locations
United States, Texas
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: Ralph DeFronzo, MD The University of Texas Health Science Center at San Antonio
Principal Investigator: Devjit Tripathy, MD The University of Texas Health Science Center at San Antonio
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party: Ralph DeFronzo, Professor, Medicine -Diabetes, The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT01439854     History of Changes
Other Study ID Numbers: 5 R01 DK024092-27/NIH Prot IV
R01DK024092 ( U.S. NIH Grant/Contract )
First Posted: September 23, 2011    Key Record Dates
Last Update Posted: July 10, 2018
Last Verified: July 2018

Keywords provided by Ralph DeFronzo, The University of Texas Health Science Center at San Antonio:
Insulin sensitivity
Mitochondrial function
Glucose toxicity
Glucosuria

Additional relevant MeSH terms:
Hypersensitivity
Insulin Resistance
Mitochondrial Diseases
Immune System Diseases
Hyperinsulinism
 Glucose Metabolism Disorders
Metabolic Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs