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

This study is currently recruiting participants. (see Contacts and Locations)

Verified January 2017 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, The University of Texas Health Science Center at San Antonio

ClinicalTrials.gov Identifier:

NCT01439854

First received: August 3, 2011

Last updated: January 20, 2017

Last verified: January 2017

History of Changes

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: 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

Resource links provided by NLM:

Genetics Home Reference related topics: ataxia neuropathy spectrum childhood myocerebrohepatopathy spectrum deoxyguanosine kinase deficiency mitochondrial neurogastrointestinal encephalopathy disease multiple mitochondrial dysfunctions syndrome myoclonic epilepsy myopathy sensory ataxia

MedlinePlus related topics: Allergy

Drug Information available for: Insulin Dapagliflozin

Genetic and Rare Diseases Information Center resources: Multiple Mitochondrial Dysfunctions Syndrome

U.S. FDA Resources

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 ]
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 ]
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:	July 2017
Estimated Primary Completion Date:	July 2017 (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)
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

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, 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 ( US NIH Grant/Contract Award Number )
Study First Received:	August 3, 2011
Last Updated:	January 20, 2017

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 May 25, 2017

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