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Mitochondrial Dysfunction and Insulin Resistance in Skeletal Muscle

Primary Purpose

Insulin Resistance

Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Intralipid, 20% Intravenous Emulsion
MitoQ
Salbutamol
Sponsored by
University of Copenhagen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Insulin Resistance

Eligibility Criteria

40 Years - 60 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Body mass index (BMI) ≥25 and <40 kg/m2
  • Fasting plasma glucose ≥ 5.6 mmol/L or HbA1c ≥ 5.7%
  • HOMA2-IR > 1.4
  • VO2max <45 ml/kg/min

Exclusion Criteria:

  • Treatment with >2 antidiabetic medications
  • Insulin usage
  • Chronic disease deemed by the study responsible medical doctor to interfere with any part of the study
  • Chronic use of prescription medicine deemed by the study responsible medical doctor to interfere with any part of the study
  • Smoking

Sites / Locations

  • August Krogh Building

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

No Intervention

Other

Arm Label

Lipid infusion + MitoQ

Lipid infusion + placebo

Control

Lipid infusion + beta2-agonist

Arm Description

Subjects undergo a hyperinsulinemic isoglycemic clamp preceded by MitoQ administration and intravenous lipid infusion

Subjects undergo a hyperinsulinemic isoglycemic clamp preceded by placebo administration and intravenous lipid infusion

Subjects undergo a hyperinsulinemic isoglycemic clamp

Subjects undergo a hyperinsulinemic isoglycemic clamp with intravenous infusion of lipid and salbutamol

Outcomes

Primary Outcome Measures

Whole body Insulin sensitivity
Whole body insulin sensitivity is determined by hyperinsulinemic isoglycemic clamp method
Skeletal muscle insulin sensitivity
Insulin-dependent skeletal muscle glucose uptake is determined by hyperinsulinemic isoglycemic clamp method integrated with measurements of femoral artery blood flow and arteriovenous difference of glucose

Secondary Outcome Measures

Mitochondrial respiration
Mitochondrial O2 flux is determined in skeletal muscle biopsies by high-resolution fluorespirometry
Mitochondrial reactive oxygen species
Mitochondrial H2O2 emission rate is determined in skeletal muscle biopsies by high-resolution fluorespirometry
Mitochondrial oxidative stress
Peroxiredoxin3 dimer/monomer ratio is determined in skeletal muscle biopsies
Muscle redox status
GSH/GSSG ratio is determined in skeletal muscle biopsies
Insulin signalling
Phosphorylation status of proteins modulating insulin action is determined in skeletal muscle biopsies

Full Information

First Posted
September 2, 2020
Last Updated
December 1, 2021
Sponsor
University of Copenhagen
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1. Study Identification

Unique Protocol Identification Number
NCT04558190
Brief Title
Mitochondrial Dysfunction and Insulin Resistance in Skeletal Muscle
Official Title
Mitochondrial Dysfunction and Insulin Resistance in Skeletal Muscle
Study Type
Interventional

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
September 2, 2020 (Actual)
Primary Completion Date
November 1, 2021 (Actual)
Study Completion Date
November 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Copenhagen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of the study is to evaluate the link between insulin resistance and alterations in skeletal muscle mitochondrial redox homeostasis

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Insulin Resistance

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lipid infusion + MitoQ
Arm Type
Experimental
Arm Description
Subjects undergo a hyperinsulinemic isoglycemic clamp preceded by MitoQ administration and intravenous lipid infusion
Arm Title
Lipid infusion + placebo
Arm Type
Placebo Comparator
Arm Description
Subjects undergo a hyperinsulinemic isoglycemic clamp preceded by placebo administration and intravenous lipid infusion
Arm Title
Control
Arm Type
No Intervention
Arm Description
Subjects undergo a hyperinsulinemic isoglycemic clamp
Arm Title
Lipid infusion + beta2-agonist
Arm Type
Other
Arm Description
Subjects undergo a hyperinsulinemic isoglycemic clamp with intravenous infusion of lipid and salbutamol
Intervention Type
Drug
Intervention Name(s)
Intralipid, 20% Intravenous Emulsion
Intervention Description
Lipid infusion
Intervention Type
Dietary Supplement
Intervention Name(s)
MitoQ
Other Intervention Name(s)
Mitoquinone mesylate, Mitoquinone, MitoQ10
Intervention Description
Oral administration of MitoQ capsules
Intervention Type
Drug
Intervention Name(s)
Salbutamol
Intervention Description
Beta2-agonist infusion
Primary Outcome Measure Information:
Title
Whole body Insulin sensitivity
Description
Whole body insulin sensitivity is determined by hyperinsulinemic isoglycemic clamp method
Time Frame
5 hours after lipid infusion
Title
Skeletal muscle insulin sensitivity
Description
Insulin-dependent skeletal muscle glucose uptake is determined by hyperinsulinemic isoglycemic clamp method integrated with measurements of femoral artery blood flow and arteriovenous difference of glucose
Time Frame
5 hours after lipid infusion
Secondary Outcome Measure Information:
Title
Mitochondrial respiration
Description
Mitochondrial O2 flux is determined in skeletal muscle biopsies by high-resolution fluorespirometry
Time Frame
Baseline
Title
Mitochondrial reactive oxygen species
Description
Mitochondrial H2O2 emission rate is determined in skeletal muscle biopsies by high-resolution fluorespirometry
Time Frame
Baseline
Title
Mitochondrial oxidative stress
Description
Peroxiredoxin3 dimer/monomer ratio is determined in skeletal muscle biopsies
Time Frame
Before (baseline) as well as 3 and 5 hours after lipid infusion
Title
Muscle redox status
Description
GSH/GSSG ratio is determined in skeletal muscle biopsies
Time Frame
Before (baseline) as well as 3 and 5 hours after lipid infusion
Title
Insulin signalling
Description
Phosphorylation status of proteins modulating insulin action is determined in skeletal muscle biopsies
Time Frame
Before (baseline) as well as 3 and 5 hours after lipid infusion
Other Pre-specified Outcome Measures:
Title
Cardiorespiratory fitness
Description
Pulmonary maximal oxygen uptake (VO2max) is determined during an incremental exercise test to exhaustion
Time Frame
Baseline
Title
Body composition
Description
Fat free mass and fat mass are determined by dual-energy X-ray absorptiometry (DXA)
Time Frame
Baseline

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Body mass index (BMI) ≥25 and <40 kg/m2 Fasting plasma glucose ≥ 5.6 mmol/L or HbA1c ≥ 5.7% HOMA2-IR > 1.4 VO2max <45 ml/kg/min Exclusion Criteria: Treatment with >2 antidiabetic medications Insulin usage Chronic disease deemed by the study responsible medical doctor to interfere with any part of the study Chronic use of prescription medicine deemed by the study responsible medical doctor to interfere with any part of the study Smoking
Facility Information:
Facility Name
August Krogh Building
City
Copenhagen
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
No

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Mitochondrial Dysfunction and Insulin Resistance in Skeletal Muscle

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