mTOR as Mediator of Insulin Sensitivity Study

NCT05233722 | Recruiting

• 1 other identifier: Rapa Study
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Insulin Sensitivity

Keywords

Exercise; Muscle insulin Sensitivity; Muscle Glucose uptake; Muscle protein synthesis; mTOR

Outcome Measures

Primary Outcomes (1)

• Insulin stimulated muscle glucose uptake

  Muscle glucose uptake during insulin stimulation in recovery from exercise (insulin sensitivity) will be determined based on Fick's principle. Thus, femoral arterio-venous difference (av difference) in blood glucose concentration will be multiplied by femoral arterial leg blood flow.

  Through study completion, approx. 1 year.

Secondary Outcomes (2)

• Insulin stimulated muscle protein synthesis

  1-2 year.

• Posttranslational modification of proteins in muscle biopsies

  5 years

Study Arms (2)

Post-exercise insulin sensitivity following placebo administration

PLACEBO COMPARATOR

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.

Other: Exercise; Procedure: Insulin infusion; Drug: Placebo

Post-exercise insulin sensitivity following Rapamycin administration

EXPERIMENTAL

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.

Other: Exercise; Procedure: Insulin infusion; Drug: Rapamycin

Interventions

Exercise OTHER

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

Post-exercise insulin sensitivity following Rapamycin administration; Post-exercise insulin sensitivity following placebo administration

Insulin infusion PROCEDURE

2 hours of Euglycemic Hyperinsulinemic Clamp

Post-exercise insulin sensitivity following Rapamycin administration; Post-exercise insulin sensitivity following placebo administration

Placebo DRUG

Administration of 800 mg of calcium tablets

Post-exercise insulin sensitivity following placebo administration

Rapamycin DRUG

Administration of 16 mg of Rapamycin tablets

Post-exercise insulin sensitivity following Rapamycin administration

Eligibility Criteria

• Age: 22 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.
• Disease during conclusion of the study

Sponsors & Collaborators

• University of Copenhagen: lead
• Danish Diabetes Academy: collaborator

Study Sites (1)

University of Copenhagen

Copenhagen, 2100, Denmark

RECRUITING

MeSH Terms

Conditions

Insulin Resistance; Motor Activity

Interventions

Exercise; Insulin Infusion Systems; Sirolimus

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Drug Delivery Systems; Drug Therapy; Therapeutics; Infusion Pumps; Equipment and Supplies; Artificial Organs; Surgical Equipment; Macrolides; Lactones; Organic Chemicals

Study Officials

• Jørgen FP Wojtaszewski, Professor

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jørgen FP Wojtaszewski, Professor

CONTACT

+4535321625; jw@nexs.ku.dk

Magnus R Larsen, MSc

CONTACT

+4540186274; Marl@nexs.ku.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The participant will be blinded upon receiving the drug. 4-5 researchers will conduct various measurements on the subject upon each experimental day. Only the clinical responsible will know which drug is administered, while the remaining researchers will be blinded.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 17, 2022
• First Posted: February 10, 2022
• Study Start: February 10, 2022
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029
• Last Updated: May 16, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)