Insulin ResistanceCOBOSNCT04178603
Copenhagen, Boston, Sydney
A study testing Exercise, insulin infusion in people with Insulin Resistance and Insulin Sensitivity, run by University of Copenhagen at 1 site in Denmark.
Trial summary
The study investigates the regulation of muscle glucose utilization during exercise and enhanced insulin sensitivity in recovery from exercise. This will be investigated in lean control subjects and obese insulin resistant subjects. Read more about this study
- Who is it for?
- Ages 25 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Insulin Resistance, Insulin Sensitivity, Type 2 Diabetes
- What is being tested?
- Exercise, insulin infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteDenmark
- Study dates
- 5 Jul 2018to 1 Sep 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 25 to 40 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 25-40 years
- Physical activity level (VO2peak) between 30-50 mL O2/min/kg
Show all 15Show fewer
- Specific for the persons of normal weight:
- BMI between 18.0 and 25.0
- HOMA-IR ≤ 1.5
- Glucose tolerant (intact response in relation to oral glucose tolerance test, OGTT)
- Without metabolic syndrome (defined by the International Diabetes Federation in 2006)
- Specific for the persons with overweight and insulin resistance:
- BMI between 28.0 and 35.0
- HOMA-IR ≥ 2.2
- Glucose tolerant (intact response in relation to OGTT)
Who cannot join
- Women
- Elevated blood pressure (systolic above 140 mmHg, diastolic above 90 mmHg).
- Persons who show signs of metabolic diseases, hematologic diseases, reduced liver function or other signs of disease that may affect the outcome of the study or the study subject's wellbeing will be excluded.
- 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.
Denmark1 site
Department of Exercise, Nutrition and Sports, Faculty of Sciences, University of Copenhagen
Copenhagen, 2100
About this study
Official title: The COpenhagen-BOston-Sydney Study, The COBOS-study
The study investigates the regulation of muscle glucose utilization during exercise and enhanced insulin sensitivity in recovery from exercise.
This will be investigated in lean control subjects and obese insulin resistant subjects.
Read the detailed description
The subjects will perform two trials (trial A and B).
Trial A: During trial A the study subject will eat a morning meal at 6:00 a.m. corresponding to 5% of the daily energy requirements and will arrive at the research laboratory at 8:00 a.m. It is requested that the study subject will arrive in a car or with public transportation. After arrival the study subject will rest for 1 hour and at that time catheters are inserted in both femoral veins and the femoral artery in one of the legs. At 9:00 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. Muscle biopsies from the m. vastus lateralis muscle in both legs will be taken before (at 8.45 a.m.), immediately after (at 10:00 a.m.) and 2 hours after conclusion of exercise (at 12:00 p.m.) (in total of 6 biopsies). 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 (at 8:20 a.m., 8:40 a.m. and 9:00 a.m.), during exercise (at 9:20 a.m., 9:40 a.m. and 10:00 a.m.) and during the recovery period after exercise (at 10:10 a.m., 10:30 a.m., 11:00 a.m., 11:30 a.m. and 12:00 p.m.). 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 12:00 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: During test trial B the study subjects will eat a morning meal at 6:00 a.m. corresponding to 5% of the daily energy requirements and will arrive at the research laboratory at 8:00 a.m. It is requested that the study subject will arrive in a car or with public transportation.
During trial B the study subjects will perform the same one-leg knee extension exercise protocol as in trial A. At 9:00 a.m. the study subject starts performing one-leg knee extension exercise for 1 hour at 80% of maximal work capacity with 3 intervals of 5 minutes duration where the load is at 100% of maximal work capacity. This work protocol ensures full activation/recruiting of all muscle fibers. After the kicking exercise is completed the study subject will rest in supine position for 6 hours. At the beginning of this resting period catheters are inserted in the femoral veins in both legs and in the femoral artery in one leg. Also catheters are inserted in each forearm vein (antecubital veins) for intravenous infusion of insulin, glucose and stable 13C(u)-glucose. Intravenous infusion of 13C(u)-glucose is started 2 hours after conclusion of exercise in order to achieve a 10% enrichment of blood glucose. 4 hours after cessation of exercise a hyperinsulinemic euglycemic clamp of 120 minutes duration is started. This implies intravenous infusion of insulin and glucose for 120 minutes in order to determine insulin sensitivity for glucose uptake and metabolism of glucose. The clamp is started with a bolus injection of insulin (9.0 mU/kg) followed by a constant infusion (1.42 mU/kg/min). Simultaneously glucose infusion rate will be adjusted so that euglycemia is maintained. Immediately before, after 30 minutes and after 120 minutes of insulin infusion a muscle biopsy is taken from the vastus lateralis muscle in both legs (a total of 6 biopsies). Blood samples from both femoral veins and one femoral artery are taken before (at 12:00 p.m., 12:30 p.m., 1:00 p.m., 1:30 p.m. and 2:00 p.m.) and during (at 2:15 p.m., 2:30 p.m., 2:45 p.m., 3:00 p.m., 3:15 p.m., 3:30 p.m., 3:45 p.m. and 4:00 p.m.) the hyperinsulinemic euglycemic clamp. Simultaneously blood flow is measured in both femoral arteries with use of Doppler technique. Determination of arteriovenous difference (AV difference) by simultaneous measurement of blood flow enables us to calculate glucose uptake and uptake/release of relevant substances (proteins, peptides and metabolites etc.). Indirect calorimetry for determination of whole body metabolism is measured concomitantly, starting 2 hours after conclusion of exercise. The experimental part of trial B is concluded at 4:00 p.m. The study subjects receive food and drink and are observed for one hour before they may leave the research laboratory.
Muscle biopsies and blood samples from trial A and B are stored in a locked -80ºC freezer. Muscle samples and blood samples will subsequently be used for miscellaneous analyses described under background.
The trials (A and B) will be carried out in a randomized order and will be separated by a minimum of 14 days.
- Conditions
- Insulin Resistance, Insulin Sensitivity, Type 2 Diabetes
- Being tested
- Exercise, insulin infusion
- Keywords
- Exercise, Insulin Resistance, Type 2 Diabetes, Glucose Uptake, Insulin Sensitivity
- Medical subject headings
- Insulin Resistance, Diabetes Mellitus, Type 2, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exercise, insulin infusionOther
Trial A: Acute one-legged exercise Trial B: Insulin infusion 4 hours after one-legged exercise
| Study group | Role | What they receive |
|---|---|---|
| Acute Exercise Trial | Experimental | Lean control subjects and insulin resistant subjects perform an acute bout of one-legged knee-extensor exercise. Glucose metabolism is investigated before exercise (basal), during exercise and for 120 min of recovery. Receives: Other: Exercise, insulin infusion |
| Insulin Sensitivity post Exercise | Experimental | Lean control subjects and insulin resistant subjects perform an acute bout of one-legged knee-extensor exercise and insulin action is investigated 4 hours after cessation of exercise. Insulin action is investigated by a 120 min euglycemic-hyperinsulinemic euglycemic clamp. Receives: Other: Exercise, insulin infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Muscle glucose uptake during exercise and enhanced insulin sensitivity in recovery from exercise.
Muscle glucose uptake during exercise and during insulin stimulation in recovery from exercise (insulin sensitivity) will be determined based on the the Fick principle. Thus, arterio-venous difference (av difference) in blood glucose will be multiplied by arterial leg blood flow.
Measured: Through study completion, an average of 1 year.
Secondary outcomes (1)
Posttranslational modification of proteins in muscle biopsies.
The obtained muscle samples will be subjected to mass spectrometry analysis. This measurement shows posttranslational modification that regulates protein function.
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 posted26 Nov 2019
- Study start5 Jul 2018
- Primary completion1 Sep 2020
- Study completion1 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Insulin ResistanceStudies of the same condition, open and under way.
- 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
- Parallel groups
- Model description
- Lean control subjects and obese insulin resistant subjects undergo two different trials (trial A and B). Trial A aims to investigate the effect of acute exercise and 2 hours recovery. Trial B aims to investigate insulin sensitivity for glucose uptake in recovery from exercise.
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer, University of Sydney
- Responsible party
- Principal investigator, Professor Jorgen FP Wojtaszewski, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04178603
- Sponsor's protocol ID
- COBOS
- Acronym
- COBOS
- Status last verified
- Apr 2021
- First submitted
- 18 Nov 2019
- Last updated
- 6 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- 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 6 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The COpenhagen-BOston-Sydney Study, The COBOS-study
- ClinicalTrials.gov ID
- NCT04178603
- Acronym / sponsor ID
- COBOS / COBOS
- Conditions
- Insulin Resistance, Insulin Sensitivity, Type 2 Diabetes
- Keywords
- Exercise, Insulin Resistance, Type 2 Diabetes, Glucose Uptake, Insulin Sensitivity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- University of CopenhagenUniversity, hospital or other
- Collaborators
- Pfizer, University of Sydney
- Study start
- 5 Jul 2018 (actual)
- Primary completion
- 1 Sep 2020 (actual)
- Study completion
- 1 Sep 2020 (actual)
- First posted
- 26 Nov 2019 (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 regulation of muscle glucose utilization during exercise and enhanced insulin sensitivity in recovery from exercise.
This will be investigated in lean control subjects and obese insulin resistant subjects.
Detailed description
The subjects will perform two trials (trial A and B).
Trial A: During trial A the study subject will eat a morning meal at 6:00 a.m. corresponding to 5% of the daily energy requirements and will arrive at the research laboratory at 8:00 a.m. It is requested that the study subject will arrive in a car or with public transportation. After arrival the study subject will rest for 1 hour and at that time catheters are inserted in both femoral veins and the femoral artery in one of the legs. At 9:00 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. Muscle biopsies from the m. vastus lateralis muscle in both legs will be taken before (at 8.45 a.m.), immediately after (at 10:00 a.m.) and 2 hours after conclusion of exercise (at 12:00 p.m.) (in total of 6 biopsies). 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 (at 8:20 a.m., 8:40 a.m. and 9:00 a.m.), during exercise (at 9:20 a.m., 9:40 a.m. and 10:00 a.m.) and during the recovery period after exercise (at 10:10 a.m., 10:30 a.m., 11:00 a.m., 11:30 a.m. and 12:00 p.m.). 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 12:00 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: During test trial B the study subjects will eat a morning meal at 6:00 a.m. corresponding to 5% of the daily energy requirements and will arrive at the research laboratory at 8:00 a.m. It is requested that the study subject will arrive in a car or with public transportation.
During trial B the study subjects will perform the same one-leg knee extension exercise protocol as in trial A. At 9:00 a.m. the study subject starts performing one-leg knee extension exercise for 1 hour at 80% of maximal work capacity with 3 intervals of 5 minutes duration where the load is at 100% of maximal work capacity. This work protocol ensures full activation/recruiting of all muscle fibers. After the kicking exercise is completed the study subject will rest in supine position for 6 hours. At the beginning of this resting period catheters are inserted in the femoral veins in both legs and in the femoral artery in one leg. Also catheters are inserted in each forearm vein (antecubital veins) for intravenous infusion of insulin, glucose and stable 13C(u)-glucose. Intravenous infusion of 13C(u)-glucose is started 2 hours after conclusion of exercise in order to achieve a 10% enrichment of blood glucose. 4 hours after cessation of exercise a hyperinsulinemic euglycemic clamp of 120 minutes duration is started. This implies intravenous infusion of insulin and glucose for 120 minutes in order to determine insulin sensitivity for glucose uptake and metabolism of glucose. The clamp is started with a bolus injection of insulin (9.0 mU/kg) followed by a constant infusion (1.42 mU/kg/min). Simultaneously glucose infusion rate will be adjusted so that euglycemia is maintained. Immediately before, after 30 minutes and after 120 minutes of insulin infusion a muscle biopsy is taken from the vastus lateralis muscle in both legs (a total of 6 biopsies). Blood samples from both femoral veins and one femoral artery are taken before (at 12:00 p.m., 12:30 p.m., 1:00 p.m., 1:30 p.m. and 2:00 p.m.) and during (at 2:15 p.m., 2:30 p.m., 2:45 p.m., 3:00 p.m., 3:15 p.m., 3:30 p.m., 3:45 p.m. and 4:00 p.m.) the hyperinsulinemic euglycemic clamp. Simultaneously blood flow is measured in both femoral arteries with use of Doppler technique. Determination of arteriovenous difference (AV difference) by simultaneous measurement of blood flow enables us to calculate glucose uptake and uptake/release of relevant substances (proteins, peptides and metabolites etc.). Indirect calorimetry for determination of whole body metabolism is measured concomitantly, starting 2 hours after conclusion of exercise. The experimental part of trial B is concluded at 4:00 p.m. The study subjects receive food and drink and are observed for one hour before they may leave the research laboratory.
Muscle biopsies and blood samples from trial A and B are stored in a locked -80ºC freezer. Muscle samples and blood samples will subsequently be used for miscellaneous analyses described under background.
The trials (A and B) will be carried out in a randomized order and will be separated by a minimum of 14 days.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Lean control subjects and obese insulin resistant subjects undergo two different trials (trial A and B). Trial A aims to investigate the effect of acute exercise and 2 hours recovery. Trial B aims to investigate insulin sensitivity for glucose uptake in recovery from exercise.
| Arm | Type | Receives |
|---|---|---|
| Acute Exercise Trial | Experimental | Other: Exercise, insulin infusionLean control subjects and insulin resistant subjects perform an acute bout of one-legged knee-extensor exercise. Glucose metabolism is investigated before exercise (basal), during exercise and for 120 min of recovery. |
| Insulin Sensitivity post Exercise | Experimental | Other: Exercise, insulin infusionLean control subjects and insulin resistant subjects perform an acute bout of one-legged knee-extensor exercise and insulin action is investigated 4 hours after cessation of exercise. Insulin action is investigated by a 120 min euglycemic-hyperinsulinemic euglycemic clamp. |
Who may qualify
- Ages
- 25 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- Healthy persons (no known disease) without diabetes in the family
- No use of medications
- Non-smokers
- Men
- Age 25-40 years
Key exclusion criteria (5 listed)
- Women
- Elevated blood pressure (systolic above 140 mmHg, diastolic above 90 mmHg).
- Persons who show signs of metabolic diseases, hematologic diseases, reduced liver function or other signs of disease that may affect the outcome of the study or the study subject's wellbeing will be excluded.
- 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
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 |
|---|---|---|
| Exercise, insulin infusionTrial A: Acute one-legged exercise Trial B: Insulin infusion 4 hours after one-legged exercise | Other | Acute Exercise Trial, Insulin Sensitivity post Exercise |
Primary outcome
Muscle glucose uptake during exercise and enhanced insulin sensitivity in recovery from exercise.
Time frame: Through study completion, an average of 1 year.
Muscle glucose uptake during exercise and during insulin stimulation in recovery from exercise (insulin sensitivity) will be determined based on the the Fick principle. Thus, arterio-venous difference (av difference) in blood glucose will be multiplied by arterial leg blood flow.
1 secondary outcome
Posttranslational modification of proteins in muscle biopsies.
Time frame: 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2022.
- 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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
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 in people with Insulin Resistance and 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 15 inclusion and 5 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: finished, as of the sponsor's last update on 6 Jan 2022. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Muscle glucose uptake during exercise and enhanced insulin sensitivity in recovery from exercise. (time frame: Through study completion, an average of 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 6 Jan 2022.