Type 2 Diabetes MellitusPhase 1NCT01240252
Insulin Receptor Substrate 1 (IRS-1) Regulation in Insulin Resistance
A Phase 1 study testing Human insulin in people with Type 2 Diabetes Mellitus, run by Mayo Clinic at 1 site in United States.
Trial summary
The study is being conducted to find out why too much fat in your blood stream may cause insulin resistance in your muscles. Insulin is the hormone, produced normally by your body, which causes your blood sugar to return to normal after you eat. Read more about this study
- Who is it for?
- Ages 30 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- Human insulin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2012to Jul 2012
- Phase
- Phase 1
- 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 30 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 30-65 y
- Healthy lean, obese, or known type 2 diabetic
- Body Mass Index (BMI) less than 36
- All nondiabetic subjects must have normal oral glucose tolerance
- Subjects must have the following laboratory values:
- Hematocrit ≥ 35 vol%
Show all 13Show fewer
- Serum creatinine ≤ 1.6 mg/dl
- Aspartate aminotransferase (AST) (SGOT)< 2 times upper limit of normal
- Alanine aminotransferase (ALT) (SGPT)< 2 times upper limit of normal
- Alkaline phosphatase < 2 times upper limit of normal
- Triglycerides < 150 mg/dl
- Prothrombin time (PT) 11.7 -14.3 seconds
- Partial thromboplastin time 23.0-37.0 seconds
Who cannot join
- No diseases known to affect glucose metabolism other than healthy type 2 diabetes
- Subjects must not be receiving any of the following medications: thiazide or furosemide diuretics, beta-blockers, or other chronic medications with known adverse effects on glucose tolerance levels unless the patient has been on stable dose of such agents for the past three months before entry into the study. Subjects may be taking a stable dose of estrogens or other hormonal replacement therapy, if the subject has been on these agents for the prior three months. Subjects taking systemic glucocorticoids are excluded.
- Subjects with a history of clinically significant heart disease (New York Heart Classification greater than grade II; more than non-specific ST-T wave changes on the EKG), peripheral vascular disease (history of claudication), or pulmonary disease (dyspnea on exertion of one flight or less; abnormal breath sounds on auscultation) will not be studied.
- Recent systemic or pulmonary embolus, untreated high-risk proliferative retinopathy, recent retinal hemorrhage, uncontrolled hypertension, systolic BP>180, diastolic BP>105, autonomic neuropathy, resting heart rate >100, electrolyte abnormalities.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Molecular Regulation of Muscle Glucose Metabolism in Man, Protocol 4
The study is being conducted to find out why too much fat in your blood stream may cause insulin resistance in your muscles. Insulin is the hormone, produced normally by your body, which causes your blood sugar to return to normal after you eat.
Read the detailed description
Insulin resistance in skeletal muscle is an early event in the pathogenesis of type 2 diabetes, obesity, and other conditions associated with the Metabolic Syndrome. The aim of this study is to determine the extent to which the inflammatory response to lipids is present in naturally occurring insulin resistance. We will test the hypothesis that skeletal muscle from insulin resistant volunteers is characterized by:
- Increased concentrations of circulating proinflammatory cytokines without changes in cytokine expression in muscle.
- Increased inflammatory response in muscle.
- Increased infiltration of inflammatory cells into skeletal muscle.
- Changes in expression of proteasome genes.
Forty five subjects will be studied in total. Three groups will be studied. One group will consist of 15 patients with type 2 diabetes mellitus The second group will consist of 15 age, gender, and body composition matched overweight or obese subjects (27 < BMI <36) with normal glucose tolerance. The third group will consist of 15 age and gender matched nonobese control subjects (BMI < 27).
There will be two visits in the study, a screening visit and the study visit. At visit 2 the subject will report to the study site having fasted since the night before, discuss the study and provide written consent, and provide a history and physical exam. Screening tests include a 12-lead resting EKG, complete blood chemistry and complete blood count (CBC), glycated hemoglobin (HbA1c), and a lipid profile. If the results of these tests show that the subject is eligible to participate in the study, a second visit will be scheduled. On the same day as the screening visit, the patient will have an oral glucose tolerance test.
Within 3 months of the screening visit, the subject will return after an overnight fast for a euglycemic clamp study and 2 muscle biopsies. Diabetic subjects will have oral medications discontinued for 3 days before study (metformin and thiazolidinedione treatment will be excluded). Patients taking insulin will have neutral protamine Hagedorn (NPH) discontinued the evening before study, and Glargine will be discontinued the morning and evening on the day before study. An antecubital catheter will be placed for infusion of substances. Deuterated glucose will be used to determine the rates of basal and insulin stimulated glucose uptake. A hand vein will be catheterized and placed in a heated box to arterialize venous blood for measurement of arterial glucose concentrations. One hour later, a percutaneous biopsy of the vastus lateralis muscle will be performed. Biopsy specimens (75-150 mg) will be frozen immediately in liquid nitrogen and stored in liquid nitrogen until they are processed. One hour after the muscle biopsy (two hours after the start of deuterated glucose), a primed-continuous (80 milliunits (mU)/(m^2 per min)) insulin infusion will be started and continued for 120 minutes to quantify the effects of insulin on glucose disposal. Throughout the insulin infusion, an infusion of 20% glucose will be adjusted to maintain euglycemia. Plasma glucose in the diabetics will be allowed to fall during the insulin infusion to euglycemia, where it will be maintained. A second muscle biopsy will be performed in the contralateral leg at the conclusion of the insulin infusion.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- Human insulin
- Keywords
- diabetes, insulin resistance
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetes Mellitus, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human insulinDrug
Also called Humulin
U100 Humulin at a rate of 80 mU/m^2 surface area per minute one time over 4 hours
| Study group | Role | What they receive |
|---|---|---|
| Type 2 Diabetes Mellitus Subjects | Experimental | Two hours after the start of deuterated glucose, subjects will receive human insulin (U100 Humulin) at a rate of 80 mU/m^2 surface area per minute one time over 4 hours. Receives: Drug: Human insulin |
| Overweight or Obese Subjects with Normal Glucose Tolerance | Experimental | Two hours after the start of deuterated glucose, subjects will receive human insulin (U100 Humulin) at a rate of 80 mU/m^2 surface area per minute one time over 4 hours. Receives: Drug: Human insulin |
| Non-Obese Control Subjects | Placebo comparator | Two hours after the start of deuterated glucose, subjects will receive human insulin (U100 Humulin) at a rate of 80 mU/m^2 surface area per minute one time over 4 hours. Receives: Drug: Human insulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of insulin resistant patients with elevated serine/threonine phosphorylation of IRS-1 in muscle.
IRS-1 will be immunoprecipitated from percutaneous muscle biopsies, resolved by gel electrophoresis, digested with trypsin, and analyzed by high-performance liquid chromatography nanospray tandem mass spectrometry (MS/MS) analysis
Measured: one month from date of volunteer study
Secondary outcomes (1)
Quantitative assay of the ability of insulin to clear glucose from the blood in insulin resistant patients.
The glucose clamp gives a quantitative measure, in mass per unit body weight per minute, of the ability of insulin to cause glucose to disappear from the blood
Measured: one month from date if volunteer study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2010 (estimated)
- Study startMar 2012
- Primary completionJul 2012
- Study completionJul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lawrence Mandarino, Mayo Clinic
- Investigators
- Lawrence Mandarino, PhD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01240252
- Sponsor's protocol ID
- 10-003382
- Other IDs
- R01DK047936
- Status last verified
- Jun 2013
- First submitted
- 29 Sep 2010
- Last updated
- 5 Jun 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular Regulation of Muscle Glucose Metabolism in Man, Protocol 4
- ClinicalTrials.gov ID
- NCT01240252
- Acronym / sponsor ID
- 10-003382
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- diabetes, insulin resistance
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Mar 2012
- Primary completion
- Jul 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 15 Nov 2010 (estimated)
- 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 is being conducted to find out why too much fat in your blood stream may cause insulin resistance in your muscles. Insulin is the hormone, produced normally by your body, which causes your blood sugar to return to normal after you eat.
Detailed description
Insulin resistance in skeletal muscle is an early event in the pathogenesis of type 2 diabetes, obesity, and other conditions associated with the Metabolic Syndrome. The aim of this study is to determine the extent to which the inflammatory response to lipids is present in naturally occurring insulin resistance. We will test the hypothesis that skeletal muscle from insulin resistant volunteers is characterized by:
- Increased concentrations of circulating proinflammatory cytokines without changes in cytokine expression in muscle.
- Increased inflammatory response in muscle.
- Increased infiltration of inflammatory cells into skeletal muscle.
- Changes in expression of proteasome genes.
Forty five subjects will be studied in total. Three groups will be studied. One group will consist of 15 patients with type 2 diabetes mellitus The second group will consist of 15 age, gender, and body composition matched overweight or obese subjects (27 < BMI <36) with normal glucose tolerance. The third group will consist of 15 age and gender matched nonobese control subjects (BMI < 27).
There will be two visits in the study, a screening visit and the study visit. At visit 2 the subject will report to the study site having fasted since the night before, discuss the study and provide written consent, and provide a history and physical exam. Screening tests include a 12-lead resting EKG, complete blood chemistry and complete blood count (CBC), glycated hemoglobin (HbA1c), and a lipid profile. If the results of these tests show that the subject is eligible to participate in the study, a second visit will be scheduled. On the same day as the screening visit, the patient will have an oral glucose tolerance test.
Within 3 months of the screening visit, the subject will return after an overnight fast for a euglycemic clamp study and 2 muscle biopsies. Diabetic subjects will have oral medications discontinued for 3 days before study (metformin and thiazolidinedione treatment will be excluded). Patients taking insulin will have neutral protamine Hagedorn (NPH) discontinued the evening before study, and Glargine will be discontinued the morning and evening on the day before study. An antecubital catheter will be placed for infusion of substances. Deuterated glucose will be used to determine the rates of basal and insulin stimulated glucose uptake. A hand vein will be catheterized and placed in a heated box to arterialize venous blood for measurement of arterial glucose concentrations. One hour later, a percutaneous biopsy of the vastus lateralis muscle will be performed. Biopsy specimens (75-150 mg) will be frozen immediately in liquid nitrogen and stored in liquid nitrogen until they are processed. One hour after the muscle biopsy (two hours after the start of deuterated glucose), a primed-continuous (80 milliunits (mU)/(m^2 per min)) insulin infusion will be started and continued for 120 minutes to quantify the effects of insulin on glucose disposal. Throughout the insulin infusion, an infusion of 20% glucose will be adjusted to maintain euglycemia. Plasma glucose in the diabetics will be allowed to fall during the insulin infusion to euglycemia, where it will be maintained. A second muscle biopsy will be performed in the contralateral leg at the conclusion of the insulin infusion.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Type 2 Diabetes Mellitus Subjects | Experimental | Drug: Human insulinTwo hours after the start of deuterated glucose, subjects will receive human insulin (U100 Humulin) at a rate of 80 mU/m^2 surface area per minute one time over 4 hours. |
| Overweight or Obese Subjects with Normal Glucose Tolerance | Experimental | Drug: Human insulinTwo hours after the start of deuterated glucose, subjects will receive human insulin (U100 Humulin) at a rate of 80 mU/m^2 surface area per minute one time over 4 hours. |
| Non-Obese Control Subjects | Placebo comparator | Drug: Human insulinTwo hours after the start of deuterated glucose, subjects will receive human insulin (U100 Humulin) at a rate of 80 mU/m^2 surface area per minute one time over 4 hours. |
Who may qualify
- Ages
- 30 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Age 30-65 y
- Healthy lean, obese, or known type 2 diabetic
- Body Mass Index (BMI) less than 36
- All nondiabetic subjects must have normal oral glucose tolerance
- Subjects must have the following laboratory values:
Key exclusion criteria (4 listed)
- No diseases known to affect glucose metabolism other than healthy type 2 diabetes
- Subjects must not be receiving any of the following medications: thiazide or furosemide diuretics, beta-blockers, or other chronic medications with known adverse effects on glucose tolerance levels unless the patient has been on stable dose of such agents for the past three months before entry into the study. Subjects may be taking a stable dose of estrogens or other hormonal replacement therapy, if the subject has been on these agents for the prior three months. Subjects taking systemic glucocorticoids are excluded.
- Subjects with a history of clinically significant heart disease (New York Heart Classification greater than grade II; more than non-specific ST-T wave changes on the EKG), peripheral vascular disease (history of claudication), or pulmonary disease (dyspnea on exertion of one flight or less; abnormal breath sounds on auscultation) will not be studied.
- Recent systemic or pulmonary embolus, untreated high-risk proliferative retinopathy, recent retinal hemorrhage, uncontrolled hypertension, systolic BP>180, diastolic BP>105, autonomic neuropathy, resting heart rate >100, electrolyte abnormalities.
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 |
|---|---|---|
| Human insulinAlso: HumulinU100 Humulin at a rate of 80 mU/m^2 surface area per minute one time over 4 hours | Drug | Non-Obese Control Subjects, Overweight or Obese Subjects with Normal Glucose Tolerance, Type 2 Diabetes Mellitus Subjects |
Primary outcome
Proportion of insulin resistant patients with elevated serine/threonine phosphorylation of IRS-1 in muscle.
Time frame: one month from date of volunteer study
IRS-1 will be immunoprecipitated from percutaneous muscle biopsies, resolved by gel electrophoresis, digested with trypsin, and analyzed by high-performance liquid chromatography nanospray tandem mass spectrometry (MS/MS) analysis
1 secondary outcome
Quantitative assay of the ability of insulin to clear glucose from the blood in insulin resistant patients.
Time frame: one month from date if volunteer study
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 5 Jun 2013.
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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.
Lawrence Mandarino, PhD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Human insulin in people with Type 2 Diabetes Mellitus, run by Mayo Clinic at 1 site in United States.
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 13 inclusion and 4 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 5 Jun 2013. 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 United States. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Proportion of insulin resistant patients with elevated serine/threonine phosphorylation of IRS-1 in muscle. (time frame: one month from date of volunteer study). 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 5 Jun 2013; AzTrials last refreshed its copy on 7 Nov 2026.