ClinicalTrials.gov
ClinicalTrials.gov Menu

Dynamics of Muscle Mitochondria in Type 2 Diabetes (DYNAMMO T2D) (DYNAMMO-T2D)

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: NCT02697201
Recruitment Status : Recruiting
First Posted : March 3, 2016
Last Update Posted : July 25, 2018
Sponsor:
Information provided by (Responsible Party):
John Kirwan, Pennington Biomedical Research Center

Brief Summary:

Insulin promotes the clearance of sugars from the blood into skeletal muscle and fat cells for use as energy; it also promotes storage of excess nutrients as fat. Type 2 diabetes occurs when the cells of the body become resistant to the effects of insulin, and this causes high blood sugar and contributes to a build-up of fat in muscle, pancreas, liver, and the heart. Understanding how insulin resistance occurs will pave the way for new therapies aimed at preventing and treating type 2 diabetes.

Mitochondria are cellular structures that are responsible for turning nutrients from food, into the energy that our cells run on. As a result, mitochondria are known as "the powerhouse of the cell." Mitochondria are dynamic organelles that can move within a cell to the areas where they are needed, and can fuse together to form large, string-like, tubular networks or divide into small spherical structures. The name of this process is "mitochondrial dynamics" and the process keeps the cells healthy. However, when more food is consumed compared to the amount of energy burned, mitochondria may become overloaded and dysfunctional resulting in a leak of partially metabolized nutrients that can interfere with the ability of insulin to communicate within the cell. This may be a way for the cells to prevent further uptake of nutrients until the current supply has been exhausted. However, long term overload of the mitochondria may cause blood sugar levels to rise and lead to the development of type 2 diabetes.

This study will provide information about the relationship between mitochondrial dynamics, insulin resistance and type 2 diabetes.


Condition or disease Intervention/treatment Phase
Insulin Resistance Drug: Intralipid Drug: Saline Early Phase 1

Detailed Description:
The traditional view of mitochondria as isolated, spherical, energy producing organelles is undergoing a revolutionary transformation. Emerging data show that mitochondria form a dynamic networked reticulum that is regulated by cycles of fission and fusion. The discovery of a number of proteins that regulate these activities has led to important advances in understanding human disease. Data show that activation of dynamin related protein 1 (Drp1), a protein that controls mitochondrial fission, is reduced following exercise in prediabetes, and the decrease is linked to increased insulin sensitivity and fat oxidation. The proposed research will test the hypothesis that mitochondrial dynamics is a key mechanism of insulin resistance in type 2 diabetes. Translational first-in-man studies will use an acute lipid challenge to investigate the physiological significance of altered skeletal muscle mitochondrial dynamics on insulin sensitivity in humans. The experimental approach harnesses innovative molecular and cellular tools, interfaced with physiologically significant human studies to obtain meaningful data on insulin resistance, and has the potential to generate insights that will lead to new diabetes therapies for future generations.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Dynamics of Muscle Mitochondria in Type 2 Diabetes (DYNAMMO-T2D)
Study Start Date : July 2016
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : February 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Intralipid Infusion, then Saline
Participants in this arm will first receive a lipid infusion. Then 4 weeks later the saline infusion.
Drug: Intralipid
0.55 ml/kg/h
Other Name: Liposyn

Drug: Saline
0.55 ml/kg/h for

Sham Comparator: Saline Infusion, then Intralipid
Participants in this arm will first receive a saline infusion. Then 4 weeks later the lipid infusion.
Drug: Intralipid
0.55 ml/kg/h
Other Name: Liposyn

Drug: Saline
0.55 ml/kg/h for




Primary Outcome Measures :
  1. Effects of lipid infusion on mitochondrial fission [ Time Frame: 5 years ]
    Fission will be assessed from quantitative measures of dynamin-related protein-1. The unit of assessment is arbitrary units of blot intensity and is expressed as AU.


Secondary Outcome Measures :
  1. Effects of lipid infusion on mitochondrial function [ Time Frame: 5 years ]
    Function will be assessed from oxygen consumption. Unit of assessment is pmol/s/mg of muscle.

  2. Insulin sensitivity [ Time Frame: 5 years ]
    Insulin sensitivity will be assessed by euglycemic hyperinsulinemic clamp. Units of assessment are mg/kg/min.



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 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy
  • Sedentary
  • Normal glucose tolerance
  • BMI <25 kg/m2

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): NCT02697201


Contacts
Contact: Christopher Axelrod, MEd 225-763-3171 Christopher.Axelrod@pbrc.edu
Contact: John P Kirwan, Ph.D. 216-444-3412 John.Kirwan@pbrc.edu

Locations
United States, Louisiana
Pennington Biomedical Research Center Recruiting
Baton Rouge, Louisiana, United States, 70808
Contact: John Kirwan       John.Kirwan@pbrc.edu   
Contact: Christopher Axelrod       Christopher.Axelrod@pbrc.edu   
Sponsors and Collaborators
Pennington Biomedical Research Center
Investigators
Principal Investigator: John P Kirwan, Ph.D. Pennington Biomedical Research Center

Responsible Party: John Kirwan, Executive Director, Pennington Biomedical Research Center
ClinicalTrials.gov Identifier: NCT02697201     History of Changes
Other Study ID Numbers: 15-1311
First Posted: March 3, 2016    Key Record Dates
Last Update Posted: July 25, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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.: No

Keywords provided by John Kirwan, Pennington Biomedical Research Center:
Mitochondrial Dynamics
Insulin Resistance

Additional relevant MeSH terms:
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Soybean oil, phospholipid emulsion
Fat Emulsions, Intravenous
Parenteral Nutrition Solutions
Pharmaceutical Solutions