mTOR as Mediator of Insulin Sensitivity Study

NCT ID: NCT05233722

Last Updated: 2024-05-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-10
• Study Completion Date: 2029-06-30

Brief Summary

The study investigates the role of mTOR in mediating enhancement of muscle insulin sensitivity following a single bout of exercise.

This will be investigated in young healthy male subjects by administering the pharmacological mTOR inhibitor Rapamycin in a crossover blinded experimental setup known to enhance muscle insulin sensitivity following one-legged knee-extensor exercise.

Detailed Description

Trial A: During trial A the study subject will arrive at the research laboratory and eat a morning meal at 6:30 a.m. corresponding to 5% of the daily energy requirements. It is requested that the study subject will arrive in a car or with public transportation. At the same time, the subject will ingest 16 mg of Rapamycin or placebo (800 mg Calcium) in pill form. Following ingestion, the study subject will rest for 2 hour and at that time catheters are inserted in both femoral veins, the femoral artery in one of the legs and in each forearm vein (antecubital veins) for later blood sampling and intravenous infusion of insulin, glucose, stable D2-glucose and stable 13C6-phenylalanine. At 8:30 a.m. the study subjects will perform one-leg knee extension exercise for 1 hour at an intensity of 80% of maximal work capacity. In this work protocol there are inserted 3 intervals of 5 minutes duration where the study subject works at 100% of maximal intensity with the purpose of securing a full activation/recruiting of all muscle fibers. Immediately following conclusion of the exercise bout 13C6-phenylalanine is infused for later determination of muscle protein synthesis. 2 hours into the recovery from exercise D2-glucose is infused for later determination of hepatic glucose production. 4 hours into the recovery from exercise an euglycaemic hyperinsulinemic clamp will be initiated for 2 hours for determination of insulin stimulated muscle glucose uptake. Muscle biopsies from the m. vastus lateralis muscle in one or both legs will be taken before, immediately after, as well as 2, 4 and 6 hours after conclusion of exercise. Pulmonary oxygen uptake is measured with the use of an online system before, during and after exercise and is used for determination of substrate metabolism. Blood samples from the femoral veins in both legs and the femoral artery in one of the legs are drawn before, during exercise, and during the recovery period after exercise. At the same time blood flow is measured in the femoral arteries in both legs with the use of Doppler technique. Determination of arteriovenous difference (AV difference) by simultaneous measurement of blood flow enables us to calculate skeletal muscle glucose uptake and uptake/release of relevant substances (proteins, peptides and metabolites etc.). The experimental part of trial A is completed at 15:30 p.m. The study subject will be given food and drink and will be observed for one hour before they may leave the research laboratory.

Trial B is an identical protocol, except that the subject will receive opposite drug from trial A (Rapamycin or placebo). Trial A and B will be separated by a minimum of 14 days.

Conditions

Insulin Sensitivity

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Post-exercise insulin sensitivity following placebo administration

Young healthy males will ingest placebo (blinded) and 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 and protein synthesis will be investigated during a 120 min euglycemic hyperinsulinemic clamp.

Group Type: PLACEBO_COMPARATOR

Exercise

Intervention Type: OTHER

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

Insulin infusion

Intervention Type: PROCEDURE

2 hours of Euglycemic Hyperinsulinemic Clamp

Placebo

Intervention Type: DRUG

Administration of 800 mg of calcium tablets

Post-exercise insulin sensitivity following Rapamycin administration

Young healthy males will ingest Rapamycin (blinded) and 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 and protein synthesis will be investigated during a 120 min euglycemic hyperinsulinemic clamp.

Group Type: EXPERIMENTAL

Exercise

Intervention Type: OTHER

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

Insulin infusion

Intervention Type: PROCEDURE

2 hours of Euglycemic Hyperinsulinemic Clamp

Rapamycin

Intervention Type: DRUG

Administration of 16 mg of Rapamycin tablets

Interventions

Exercise

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

Intervention Type: OTHER

Insulin infusion

2 hours of Euglycemic Hyperinsulinemic Clamp

Intervention Type: PROCEDURE

Placebo

Administration of 800 mg of calcium tablets

Intervention Type: DRUG

Rapamycin

Administration of 16 mg of Rapamycin tablets

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy persons (no known disease) without diabetes in the family
• No use of medications
• Non-smokers
• Men
• Age 22-35 years
• Physical activity level (VO2peak) between 30-50 mL O2/min/kg
• BMI between 18.0 and 25.0

Exclusion Criteria

• Women
• Physical activity (e.g., running, cycling, fitness, etc.) above 6 hours a week.
• Persons who show signs of metabolic diseases, hematologic diseases, reduced liver function, human immunodeficiency virus (HIV), hepatitis, thyroid diseases or other signs of disease that may affect the outcome of the study or the study subject's wellbeing will be excluded.
• Acute sickness less than 2 weeks prior to study start.
• If disease appears or is identified and/or a need for medication arises after inclusion but before initiation of the study.

Disease during conclusion of the study

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

Sponsors

Danish Diabetes Academy

OTHER

Sponsor Role: collaborator

University of Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Professor Jorgen FP Wojtaszewski

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jørgen FP Wojtaszewski, Professor

Role: PRINCIPAL_INVESTIGATOR

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

Locations

University of Copenhagen

Copenhagen, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Jørgen FP Wojtaszewski, Professor

Role: CONTACT

jw@nexs.ku.dk

+4535321625

Magnus R Larsen, MSc

Role: CONTACT

Marl@nexs.ku.dk

+4540186274

Facility Contacts

Jørgen FP Wojtaszewski, Professor

Role: primary

Jw@nexs.ku.dk

+4535321625

Other Identifiers

Rapa Study

Identifier Type: -

Identifier Source: org_study_id