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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by The University of Texas Health Science Center at San Antonio
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Ralph DeFronzo, MD, The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier:
NCT01439854
First received: August 3, 2011
Last updated: July 13, 2016
Last verified: July 2016
  Purpose
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 Intervention
Insulin Sensitivity
Multiple Mitochondrial Dysfunctions Syndrome
Drug: Dapagliflozin
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by The University of Texas Health Science Center at San Antonio:

Primary Outcome Measures:
  • Change in Insulin Sensitivity [ Time Frame: baseline, two weeks ] [ Designated as safety issue: No ]
    The change in insulin sensitivity and total glucose disposal measured at two weeks with the insulin clamp compared to baseline.


Secondary Outcome Measures:
  • Change in Mitochondrial Function [ Time Frame: baseline, two weeks ] [ Designated as safety issue: No ]
    The change in mitochondrial function/gene expression at two weeks compared to baseline.


Estimated Enrollment: 30
Study Start Date: March 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • T2DM
  • Drug Naive Or On Oral Therapy

Exclusion Criteria:

  • Insulin Treatment
  • Major Organ Disease
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01439854

Contacts
Contact: Aurora Merovci 210-567 4686
Contact: Carolina Solis 210-567-4686

Locations
United States, Texas
Diabetes Division, UTHSCSA Recruiting
San Antonio, Texas, United States, 78229
Contact: Irma    210-567-4686      
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
  More Information

Responsible Party: Ralph DeFronzo, MD, 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 
Study First Received: August 3, 2011
Last Updated: July 13, 2016
Health Authority: United States: Food and Drug Administration
United States: Federal Government
United States: Institutional Review Board

Keywords provided by 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

ClinicalTrials.gov processed this record on July 28, 2016