Ischemia-reperfusion Exercise Study

NCT ID: NCT04872426

Last Updated: 2022-01-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-31
• Study Completion Date: 2020-01-03

Brief Summary

The study investigates the relationship between activation of AMP-activated protein kinase (AMPK) in human skeletal muscle and the subsequent improvement in muscle insulin sensitivity for the stimulation of glucose uptake.

This will be investigated in young healthy lean male subjects.

Detailed Description

This study aims to demonstrate the association between AMPK activation and increased insulin sensitivity in human skeletal muscle. The investigators intend to examine insulin sensitivity after various levels of AMPK activation in skeletal muscle that includes exercise at different intensities as well as exercise combined with leg blood flow restriction (ischemia). The hypothesis is that exercise combined with ischemia will result in an increased activation of AMPK compared to exercise alone, and therefore it is expected that exercise combined with ischemia will result in the greatest improvement in muscle insulin sensitivity.

Methods:

The main experiment consists of 3 experimental days (A, B and C), separated by a minimum of 14 days and carried out in a randomised order. On all the study days, the participants will arrive in the laboratory after an overnight fast. Catheters will be placed in both femoral veins and in one femoral artery. A muscle biopsy will be obtained from vastus lateralis of one leg (resting leg). Experiment A consists of one-legged muscle work for 1 hour at 70% of the leg maximum aerobic work capacity with the other leg serving as a resting control. In experiment B, the same work are performed, but with periodic at the same constricting the blood supply to the working leg (25 seconds every 2 min). Experiment C consists of one-legged muscle work for 1 hour at 70% and 95% of the leg maximum aerobic work capacity (alternately every 5 min). Immediately after each type of exercise a biopsy will be obtained from the exercising leg and the participants will rest in the fasted state for 3 hours before a third set of muscle biopsies (from both legs) will be obtained. Subsequently, insulin sensitivity will be evaluated in the participants during a 2-hour physiological hyperinsulinemic euglycemic clamp. By the end of the clamp, a final set of biopsies (both legs) will be obtained. Throughout the study day sampling of artery and venous blood/plasma samples allows for the estimation of substrate extraction by the two legs. Further, measures of artery blood flow by Ultrasound Doppler technique allow for the final calculation of substrate uptake/release across the two legs before exercise, during exercise and in recovery from exercise. Importantly, the ability for insulin to stimulate these processes can be evaluated in both a rested and in a prior exercised leg.

Conditions

Insulin Sensitivity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Low intensity exercise

70% of maximal leg work load capacity

Group Type: EXPERIMENTAL

Exercise, insulin infusion

Intervention Type: OTHER

Acute one-legged exercise, Insulin infusion 3 hours after one-legged exercise

High intensity exercise

70% and 95% of maximal work load capacity (alternately every 5 min)

Group Type: EXPERIMENTAL

Exercise, insulin infusion

Intervention Type: OTHER

Acute one-legged exercise, Insulin infusion 3 hours after one-legged exercise

Low intensity exercise + intermittent ischemia-reperfusion

70% of maximal leg work load capacity with intermittent ischemia (25 seconds every 2 min)

Group Type: EXPERIMENTAL

Exercise, insulin infusion

Intervention Type: OTHER

Acute one-legged exercise, Insulin infusion 3 hours after one-legged exercise

Interventions

Exercise, insulin infusion

Acute one-legged exercise, Insulin infusion 3 hours after one-legged exercise

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• normal weight (BMI: below or equal to 27)
• physical active on a regular basis
• cardiorespiratory fitness between 40-60 ml/kg/min
• no history or sign of type 2 diabetes, hypertension, insulin resistance or dyslipidemia

Exclusion Criteria

• smoker
• BMI: above 27
• using any kind of medication

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Professor Jorgen FP Wojtaszewski

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Department of Exercise, Nutrition and Sports, Faculty of Sciences, University of Copenhagen

Copenhagen, , Denmark

Countries

Denmark

Other Identifiers

Ischemia

Identifier Type: -

Identifier Source: org_study_id