search
Back to results

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

Primary Purpose

Insulin Sensitivity, Multiple Mitochondrial Dysfunctions Syndrome

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Dapagliflozin
Placebo
Sponsored by
The University of Texas Health Science Center at San Antonio
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Insulin Sensitivity focused on measuring Insulin sensitivity, Mitochondrial function, Glucose toxicity, Glucosuria

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • T2DM
  • Drug Naive Or On Oral Therapy

Exclusion Criteria:

  • Insulin Treatment
  • Major Organ Disease

Sites / Locations

  • Diabetes Division, UTHSCSA

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Dapagliflozin

Arm Description

this arm is control

Interventional arm

Outcomes

Primary Outcome Measures

Change in Insulin Sensitivity
The change in insulin sensitivity and total glucose disposal measured at two weeks with the insulin clamp compared to baseline. This is measured using TGD (whole body tissue glucose disposal)/SSPI (steady state plasma insulin concentration) ratio

Secondary Outcome Measures

Change in Mitochondrial Function
The change in mitochondrial function/gene expression at two weeks compared to baseline. This was measured by energy expenditure.

Full Information

First Posted
August 3, 2011
Last Updated
October 10, 2019
Sponsor
The University of Texas Health Science Center at San Antonio
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
search

1. Study Identification

Unique Protocol Identification Number
NCT01439854
Brief Title
Study of Dapagliflozin on Mitochondrial Dysfunction and Impaired Insulin Signaling/Action
Acronym
DAPA MITO
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 Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
March 2011 (undefined)
Primary Completion Date
June 30, 2018 (Actual)
Study Completion Date
June 30, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The University of Texas Health Science Center at San Antonio
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Data Monitoring Committee
No

5. Study Description

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].
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Insulin Sensitivity, Multiple Mitochondrial Dysfunctions Syndrome
Keywords
Insulin sensitivity, Mitochondrial function, Glucose toxicity, Glucosuria

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
this arm is control
Arm Title
Dapagliflozin
Arm Type
Experimental
Arm Description
Interventional arm
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin
Intervention Description
Treatment arm, 10 mg per day for 2 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Patients are treated with placebo
Primary Outcome Measure Information:
Title
Change in Insulin Sensitivity
Description
The change in insulin sensitivity and total glucose disposal measured at two weeks with the insulin clamp compared to baseline. This is measured using TGD (whole body tissue glucose disposal)/SSPI (steady state plasma insulin concentration) ratio
Time Frame
baseline, two weeks
Secondary Outcome Measure Information:
Title
Change in Mitochondrial Function
Description
The change in mitochondrial function/gene expression at two weeks compared to baseline. This was measured by energy expenditure.
Time Frame
baseline, two weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: T2DM Drug Naive Or On Oral Therapy Exclusion Criteria: Insulin Treatment Major Organ Disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ralph DeFronzo, MD
Organizational Affiliation
The University of Texas Health Science Center at San Antonio
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Devjit Tripathy, MD
Organizational Affiliation
The University of Texas Health Science Center at San Antonio
Official's Role
Principal Investigator
Facility Information:
Facility Name
Diabetes Division, UTHSCSA
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States

12. IPD Sharing Statement

Links:
URL
https://care.diabetesjournals.org/content/39/11/2036
Description
ADA Diabetes Care 2016 Nov; 39(11): 2036-2041

Learn more about this trial

Study of Dapagliflozin on Mitochondrial Dysfunction and Impaired Insulin Signaling/Action

We'll reach out to this number within 24 hrs