Physical Activity and Insulin Sensitivity Dynamics

NCT ID: NCT06776094

Last Updated: 2025-12-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-05
• Study Completion Date: 2027-01-31

Brief Summary

The study investigates the role of one single bout of exercise in mediating enhancement of muscle insulin sensitivity following a single bout of exercise. Furthermore, the study is aiming to elucidate the temporal development in insulin signaling, at the early timepoints of insulin stimulation that may be responsible for the enhanced muscle insulin sensitivity.

This will be investigated in young healthy males subjected to a one-legged knee-extensor exercise followed by a hyperinsulinemic-euglycemic clamp, a setup known to enhance muscle insulin sensitivity.

Detailed Description

The participant arrives fasting at 8:00 AM, having abstained from alcohol, nicotine, and caffeine for the past 24 hours and refrained from strenuous physical activity for the past 48 hours. The participants are then subjected to a one-legged knee extension exercise performed by the participant from 9:00 AM to 10:00 AM.

Groin catheters are inserted into the femoral artery and vein using ultrasound guidance and sterile technique

Two hours after the completion of the exercise, a catheter is inserted into an arm vein (antecubital vein) and groin catheters are inserted into the femoral artery and vein using ultrasound guidance and sterile technique. Four hours after the exercise ends, a hyperinsulinemic-euglycemic clamp is commenced. The clamp begins with a bolus injection of insulin, followed by a continuous infusion. Glucose is infused concurrently to maintain constant blood glucose levels.

Throughout the procedure, blood samples are collected every 5 minutes from the femoral catheters, and blood flow is measured using ultrasound Doppler. Muscle biopsies from the vastus lateralis of both legs are taken before the clamp starts and at 3, 6, 10, and 20 minutes after the clamp's initiation. Following the 20-minute mark, the clamp continues until steady-state is achieved to determine tissue-specific and whole-body insulin sensitivity.

Over the course of the experiment, a total of 10 muscle biopsies and approximately 150 mL of blood are collected. The experimental part of the study is expected to conclude by 4:30 PM. Participants are provided with food and beverages and observed for 1 hour before being allowed to leave the research laboratory.

Conditions

Insulin Sensitivity

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Post-exercise insulin sensitivity

Young healthy males will perform a single bout of knee-extensor exercise and insulin action is investigated 4 hours after cessation of exercise. Insulin action towards muscle glucose uptake will be investigated during a 120 min euglycemic hyperinsulinemic clamp.

Group Type: EXPERIMENTAL

One-legged-knee extensor exercise

Intervention Type: OTHER

1 hour of one-legged-knee-extensor exercise followed by 4 hours of rest

Insulin infusion

Intervention Type: PROCEDURE

The hyperinsulinemic-euglycemic clamp is a well-established and recognized method for determining glucose uptake at a specific insulin infusion rate. It is a technique with which we have 25 years of uncomplicated experience. During the clamp, insulin (human recombinant insulin) is infused (1.42 mU/kg/min) into an arm vein (antecubital vein), while glucose (20% solution) is administered in an amount adjusted to maintain blood glucose (plasma glucose concentration) at basal levels.

The amount of insulin administered raises the participant's plasma insulin concentration (blood concentration) to approximately 100 μU/mL, which is considered within the physiological range. Blood samples are collected and analyzed continuously for glucose content, allowing for the determination of glucose uptake at the whole-body level and across the legs.

Later, these blood samples will also be analyzed for relevant metabolites and proteins, including insulin, to assess the metabolism of these substances.

Muscle Biopsy Medication: Lidocaine

Intervention Type: PROCEDURE

During supine rest, the skin on the outer thigh, approximately 15 cm above the knee, is disinfected with chlorhexidine alcohol. Subsequently, 3-4 mL of local anesthetic (lidocaine 20 mg/mL) is administered into the skin, subcutaneous tissue, and the upper portion of the muscle using a very thin needle. A pinprick test is performed after a few minutes to ensure the anesthetic is effective.

A small incision is then made in the skin and subcutaneous tissue to allow the biopsy needle to pass through to the muscle. Using the biopsy needle, a small sample of muscle tissue (approximately 150 mg) is collected. This may cause some discomfort but is very brief (~1-2 seconds). The needle is removed, a sterile dressing is applied, and the participant can leave the facility after completing the study.

The biopsy may result in mild muscle soreness for 2-3 days, similar to a minor muscle bruise. Regular physical activities can be resumed after the biopsy. However, it is advised to avoid swimming.

Exercise

Intervention Type: OTHER

The participants' maximal oxygen uptake is determined through a test on a cycle ergometer before the start of the experiment. The test begins with a 20-minute warm-up at two different low workloads, after which the workload is gradually increased until the predetermined cadence can no longer be maintained, or the participant indicates exhaustion. During the test, the participant's exhaled air is collected. After completing the warm-up, it typically takes between 4 and 7 minutes to complete the test.

Interventions

One-legged-knee extensor exercise

1 hour of one-legged-knee-extensor exercise followed by 4 hours of rest

Intervention Type: OTHER

Insulin infusion

The hyperinsulinemic-euglycemic clamp is a well-established and recognized method for determining glucose uptake at a specific insulin infusion rate. It is a technique with which we have 25 years of uncomplicated experience. During the clamp, insulin (human recombinant insulin) is infused (1.42 mU/kg/min) into an arm vein (antecubital vein), while glucose (20% solution) is administered in an amount adjusted to maintain blood glucose (plasma glucose concentration) at basal levels.

The amount of insulin administered raises the participant's plasma insulin concentration (blood concentration) to approximately 100 μU/mL, which is considered within the physiological range. Blood samples are collected and analyzed continuously for glucose content, allowing for the determination of glucose uptake at the whole-body level and across the legs.

Later, these blood samples will also be analyzed for relevant metabolites and proteins, including insulin, to assess the metabolism of these substances.

Intervention Type: PROCEDURE

Muscle Biopsy Medication: Lidocaine

During supine rest, the skin on the outer thigh, approximately 15 cm above the knee, is disinfected with chlorhexidine alcohol. Subsequently, 3-4 mL of local anesthetic (lidocaine 20 mg/mL) is administered into the skin, subcutaneous tissue, and the upper portion of the muscle using a very thin needle. A pinprick test is performed after a few minutes to ensure the anesthetic is effective.

A small incision is then made in the skin and subcutaneous tissue to allow the biopsy needle to pass through to the muscle. Using the biopsy needle, a small sample of muscle tissue (approximately 150 mg) is collected. This may cause some discomfort but is very brief (~1-2 seconds). The needle is removed, a sterile dressing is applied, and the participant can leave the facility after completing the study.

The biopsy may result in mild muscle soreness for 2-3 days, similar to a minor muscle bruise. Regular physical activities can be resumed after the biopsy. However, it is advised to avoid swimming.

Intervention Type: PROCEDURE

Exercise

The participants' maximal oxygen uptake is determined through a test on a cycle ergometer before the start of the experiment. The test begins with a 20-minute warm-up at two different low workloads, after which the workload is gradually increased until the predetermined cadence can no longer be maintained, or the participant indicates exhaustion. During the test, the participant's exhaled air is collected. After completing the warm-up, it typically takes between 4 and 7 minutes to complete the test.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Healthy individuals (no known diseases)
• No use of medication
• Non-smokers
• Male
• Aged 22-35 years
• Fitness level (VO2max, i.e., maximal oxygen uptake) between 30-50 mL O2/min/kg
• BMI between 28 and 35

• Physical activity level (e.g., running, cycling, fitness, etc.) exceeding 6 hours per week
• Acute illness within 2 weeks prior to the study days
• Use of recreational drugs within 2 weeks prior to the study days

Exclusion Criteria

• Women

• Minimum Eligible Age: 22 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Jorgen FP Wojtaszewski

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jørgen FP Wojtaszewski, Prodessor

Role: PRINCIPAL_INVESTIGATOR

Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark

Locations

University of Copenhagen, August Krogh Section for Human and Molecular Physiology

Copenhagen, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Jørgen FP Wojtaszewski, Professor

Role: CONTACT

jw@nexs.ku.dk

+4535321625

Nicolai S Henriksen, MSc

Role: CONTACT

nsh@nexs.ku.dk

+4560110222

Facility Contacts

Jørgen FP Wojtaszewski, Professor

Role: primary

jw@nexs.ku.dk

+4535321625

Other Identifiers

TEMPO

Identifier Type: -

Identifier Source: org_study_id