Insulin SensitivityNCT05233722
mTOR as Mediator of Insulin Sensitivity Study
A study testing Exercise, Insulin infusion and Rapamycin in people with Insulin Sensitivity, run by University of Copenhagen at 1 site in Denmark.
Trial 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… Read more about this study
- Who is it for?
- Ages 22 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Insulin Sensitivity
- What is being tested?
- Exercise, Insulin infusion and Rapamycin
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteDenmark
- Study dates
- 10 Feb 2022to Jun 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 to 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark1 site, 1 recruiting
- Recruiting
University of Copenhagen
Copenhagen, 2100
Jørgen FP Wojtaszewski, Professor, +4535321625, Jw@nexs.ku.dk
About this study
Official title: Mechanistic Target of Rapamycin (mTOR) as Mediator of Exercise-induced Insulin Sensitivity Study
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.
Read the 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
- Being tested
- Exercise, Insulin infusion, Placebo, Rapamycin
- Keywords
- Exercise, Muscle insulin Sensitivity, Muscle Glucose uptake, Muscle protein synthesis, mTOR
- Medical subject headings
- Insulin Resistance, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ExerciseOther
1 hour of one-legged knee-extensor exercise followed by 4 hours of rest
Insulin infusionProcedure or surgery
2 hours of Euglycemic Hyperinsulinemic Clamp
PlaceboDrug
Administration of 800 mg of calcium tablets
RapamycinDrug
Administration of 16 mg of Rapamycin tablets
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Exercise; Procedure: Insulin infusion; Drug: Rapamycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Through study completion, approx. 1 year.
Secondary outcomes (2)
Insulin stimulated muscle protein synthesis
Muscle protein synthesis during insulin stimulation in recovery from exercise will be determined based on incorporation of 13C6-phenylalanine in muscle biopsies. Unit of measure is fractional synthesis rate (FSR) in percentage per hour (%/h).
Measured: 1-2 year.
Posttranslational modification of proteins in muscle biopsies
The obtained muscle samples will be subjected to mass spectrometry-based phosphoproteomic analysis. This measurement shows posttranslational modification that regulates protein function and will reveal the signalling network underlying the interventions studied. Unit of measure is log2-transformed arbitrary units.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2022
- Study start10 Feb 2022
- Primary completionJun 2029 (estimated)
- Study completionJun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Insulin SensitivityStudies of the same condition, open and under way.
- More trials run by University of CopenhagenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- Danish Diabetes Academy
- Responsible party
- Principal investigator, Professor Jorgen FP Wojtaszewski, University of Copenhagen
- Investigators
- Jørgen FP Wojtaszewski, Professor, Principal investigator, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05233722
- Sponsor's protocol ID
- Rapa Study
- Status last verified
- May 2024
- First submitted
- 17 Jan 2022
- Last updated
- 16 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanistic Target of Rapamycin (mTOR) as Mediator of Exercise-induced Insulin Sensitivity Study
- ClinicalTrials.gov ID
- NCT05233722
- Acronym / sponsor ID
- Rapa Study
- Conditions
- Insulin Sensitivity
- Keywords
- Exercise, Muscle insulin Sensitivity, Muscle Glucose uptake, Muscle protein synthesis, mTOR
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- University of CopenhagenUniversity, hospital or other
- Collaborators
- Danish Diabetes Academy
- Study start
- 10 Feb 2022 (actual)
- Primary completion
- Jun 2029 (estimated)
- Study completion
- Jun 2029 (estimated)
- First posted
- 10 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Post-exercise insulin sensitivity following placebo administration | Placebo comparator | Other: Exercise, Procedure: Insulin infusion, Drug: PlaceboYoung 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. |
| Post-exercise insulin sensitivity following Rapamycin administration | Experimental | Other: Exercise, Procedure: Insulin infusion, Drug: RapamycinYoung 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. |
Who may qualify
- Ages
- 22 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Healthy persons (no known disease) without diabetes in the family
- No use of medications
- Non-smokers
- Men
- Age 22-35 years
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Exercise1 hour of one-legged knee-extensor exercise followed by 4 hours of rest | Other | Post-exercise insulin sensitivity following Rapamycin administration, Post-exercise insulin sensitivity following placebo administration |
| Insulin infusion2 hours of Euglycemic Hyperinsulinemic Clamp | Procedure or surgery | Post-exercise insulin sensitivity following Rapamycin administration, Post-exercise insulin sensitivity following placebo administration |
| PlaceboAdministration of 800 mg of calcium tablets | Drug | Post-exercise insulin sensitivity following placebo administration |
| RapamycinAdministration of 16 mg of Rapamycin tablets | Drug | Post-exercise insulin sensitivity following Rapamycin administration |
Primary outcome
Insulin stimulated muscle glucose uptake
Time frame: Through study completion, approx. 1 year.
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.
2 secondary outcomes
Insulin stimulated muscle protein synthesis
Time frame: 1-2 year.
Posttranslational modification of proteins in muscle biopsies
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jørgen FP Wojtaszewski, Professor principal investigator
Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exercise, Insulin infusion and Rapamycin in people with Insulin Sensitivity, run by University of Copenhagen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jørgen FP Wojtaszewski, Professor (+4535321625, jw@nexs.ku.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Insulin stimulated muscle glucose uptake (time frame: Through study completion, approx. 1 year.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2024.