Insulin ResistancePhase 1GISTNCT06592261
Graded Insulin Suppression Test P&F
A Phase 1 study testing Insulin regular, 2.0-3.2 mU/m2/min (euinsulinemia), Insulin regular, 32 mU/m2/min (hyperinsulinemia) and Octreotide Acetate, 6-45 ng/kg/min in people with Insulin Resistance and Hyperinsulinemia, run by Columbia University at 1 site in United States.
Trial summary
The goal of this study is to learn about how the hormone insulin controls blood sugar in a variety of people. The main question it aims to answer is about how much insulin the body actually needs to maintain a normal blood sugar level. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Insulin Resistance, Hyperinsulinemia, Obesity
- What is being tested?
- Insulin regular, 2.0-3.2 mU/m2/min (euinsulinemia), Insulin regular, 32 mU/m2/min (hyperinsulinemia) and Octreotide Acetate, 6-45 ng/kg/min
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Sep 2024to 13 Oct 2026
- 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 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Body mass index of 18-25 and 30-45 kg/m2
- Able to understand written and spoken English and/or Spanish
- Fasting euinsulinemia (fasting serum insulin of 4-10 μU/mL) for reference group or hyperinsulinemia (fasting serum insulin ≥ 13 μU/mL) for hyperinsulinemic group on screening labs
- Written informed consent (in English or Spanish) and any locally required authorization (e.g., Health Insurance Portability and Accountability Act) obtained from the participant prior to performing any protocol-related procedures, including screening evaluations.
Who cannot join
- Unable to provide informed consent in English or Spanish
- Unwillingness to use only bedpan or urinal to void or to refrain from non-emergent mobile device use during the GIST
- Documented weight loss of ≥ 5% of baseline within the previous 6 months
- Systolic blood pressure < 90 mm Hg or > 160 mm Hg, and/or
- Diastolic blood pressure < 60 mm Hg or > 100 mm Hg
- Abnormal resting heart rate: < 60 or ≥ 110 bpm
Show all 92Show fewer
- Sinus brady or tachycardia that has been worked up and considered benign by the recruit's personal physician may be permitted at the PI's discretion
- Abnormal screening electrocardiogram (or if on file, performed within previous 90 d):
- Non-sinus rhythm
- Heart conduction blocks
- Previously unknown ischaemic changes that persist on repeat EKG:
- ST elevations
- T-wave inversions in a vascular distribution
- Hemoglobin A1c ≥ 5.7%, and/or
- Fasting plasma glucose ≥ 100 mg/dL
- Positive qualitative β-hCG (i.e., pregnancy test) in women of childbearing potential
- Positive urine drug screen, except for lawfully prescribed medications and/or marijuana, provided that participant agrees to refrain from marijuana use during the period that they refrain from alcohol.
- Transaminases (AST or ALT) > 3.0 x the upper limit of normal
- Total bilirubin > 1.25 x the upper limit of normal
- Abnormal sodium, potassium, chloride, or bicarbonate levels that are considered potentially significant according to the clinical judgment of the PI.
- Creatinine equating to estimated glomerular filtration rate < 60 mL min-1 1.73 m-2
- Hemoglobin < 10 g/dL or hematocrit < 30%
- Platelet count < 100,000/μL
- Women currently pregnant, measured by serum and/or urine β-hCG
- Women currently breastfeeding
- History of having met any of the American Diabetes Association's definitions of prediabetic state during adulthood or diabetes mellitus (i.e., overt diabetes) at any time:
- Hemoglobin A1c ≥ 5.7%, or rapid rise in documented HbA1c values causing clinical concern for evolving insulin deficiency
- Plasma glucose ≥ 100 mg/dL after 8-h fast
- Plasma glucose of ≥ 140 mg/dL at 2 h after ingestion of a 75-g glucose load
- Random plasma glucose ≥ 200 mg/dL associated with typical hyperglycemic symptoms, diabetic ketoacidosis, or hyperglycemic-hyperosmolar state
- History of gestational diabetes mellitus within the previous 5 years
- Use of most antidiabetic medications within the 30 days prior to screening
- Excluded: thiazolidinediones, sulfonylureas, meglitinides, DPP4 inhibitors, GLP-1 receptor agonists, SGLT2 inhibitors, amylin mimetics, acarbose, insulin
- Metformin is acceptable provided that recruits meet all of the inclusion criteria at screening
- Known, documented history, at the time of screening, of any of the following medical conditions:
- Pancreatic pathology, including but not limited to: Pancreatic neoplasia (unless appropriately evaluated and considered benign and not producing hormones), Chronic pancreatitis, History of acute pancreatitis within the past 5 years
- Cardiovascular diseases (N.B. uncomplicated hypertension is not exclusionary)
- Atherosclerotic cardiovascular disease
- Stable or unstable angina
- Myocardial infarction
- Ischaemic or hemorrhagic stroke
- Peripheral arterial disease (claudication)
- Use of dual antiplatelet therapy (aspirin + P2Y12 inhibitor)
- History of percutaneous coronary intervention
- Heart rhythm abnormalities (non-sinus)
- Congestive heart failure of any New York Heart Association class
- Severe valvular heart disease (e.g., aortic stenosis)
- Pulmonary hypertension
- Chronic kidney disease, Stage 3 or higher (estimated glomerular filtration rate < 60 mL/min/1.73 m2), of any cause
- Advanced or severe liver disease, including but not limited to:
- Advanced liver fibrosis, as determined by non-invasive testing
- Cirrhosis of any etiology
- Autoimmune hepatitis or other rheumatologic disorder affecting the liver
- Biliopathy (e.g., progressive sclerosing cholangitis, primary biliary cholangitis)
- Hepatocellular carcinoma
- Infiltrative disorders (e.g., sarcoidosis, hemochromatosis, Wilson disease)
- Gallstone disease, including:
- Biliary colic (active)
- History of acute cholecystitis not treated with cholecystectomy
- History of other gallstone complications (e.g., pancreatitis, cholangitis)
- Chronic viral illness (N.B. diagnosis based only on medical history and not by laboratory confirmation)
- Hepatitis B virus (HBV), unless previously successfully eradicated with antiviral drugs that have been discontinued for at least 30 d prior to screening
- Hepatitis C virus (HCV) infection, unless previously successfully eradicated with antiviral drugs that have been discontinued for at least 30 d prior to screening
- Human immunodeficiency virus (HIV) infection
- Active seizure disorder (including controlled with antiepileptic drugs)
- Psychiatric diseases causing functional impairment that:
- Are or have been decompensated within 1 year of screening, and/or
- Require use of anti-dopaminergic antipsychotic drugs associated with significant weight gain/metabolic dysfunction (e.g., clozapine, olanzapine), monoamine oxidase inhibitors, tricyclic antidepressants, or lithium
- Other endocrinopathies:
- Cushing syndrome (okay if considered in remission after treatment, provided that no exogenous corticosteroids or other ongoing treatment are required)
- Adrenal insufficiency
- Primary aldosteronism
- Venous thromboembolic disease (deep vein thrombosis or pulmonary embolism) or any required use of therapeutic anticoagulation
- Bleeding disorders, including due to anticoagulation, or significant anemia
- Active malignancy, or hormonally active benign neoplasm, except allowances for:
- Non-melanoma skin cancer
- Differentiated thyroid cancer (AJCC Stage I only)
- Clinical concern for increased risk of volume overload, including due to medications and/or heart/liver/kidney problems, as listed above
- Clinical concern for increased risk of hypokalemia, including low potassium on screening labs (i.e., below lower limit of normal), use of certain medications, or any medical conditions listed above
- Use of prescribed medications used for any of the indications in the preceding list of excluded conditions, or their use within 30 d prior to screening, except allowances for:
- Use of drugs prescribed for indications other than the exclusionary diagnoses/purposes listed above (e.g., antiepileptic drugs used for non-seizure indications, ACEi/ARB used for uncomplicated hypertension rather than for congestive heart failure, etc.). Note, as above, that antidiabetic drugs except metformin within 30 d of screening are excluded.
- Oral or parenteral corticosteroids (at greater than prednisone 5 mg daily, or equivalent) for more than 3 days within the previous 30 days; topical and inhaled formulations are permitted.
- Beta blockers or non-dihydropyridine calcium channel blockers (verapamil or diltiazem)
- History of certain weight-loss (bariatric) surgery, including:
- Roux-en-Y gastric bypass
- Biliopancreatic diversion
- Restrictive procedures (lap band, sleeve gastrectomy) performed within the past 6 months
- Clinical concern for alcohol overuse, including recent documented history during screening and/or participant report of regularly consuming more than 2 drinks per day for males or 1 drink per day for females.
- History of severe infection or ongoing febrile illness within 14 days of screening
- Any other disease, condition, or laboratory value that, in the opinion of the investigator, would place the participant at an unacceptable risk and/or interfere with the analysis of study data.
- Known allergy/hypersensitivity to any component of the medicinal product formulations, foods, IV infusion equipment, plastics, adhesive or silicone, history of infusion site reactions with IV administration of other medicines, or ongoing clinically important allergy/hypersensitivity as judged by the investigator.
- Concurrent enrollment in another clinical study of any investigational drug therapy within 30 days prior to screening or within 5 half-lives of an investigational agent, whichever is longer.
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Irving Medical Center
New York, New York, 10032
About this study
Official title: Human Models of Selective Insulin Resistance: Graded Insulin Suppression Test (GIST) Pilot & Feasibility Study
The goal of this study is to learn about how the hormone insulin controls blood sugar in a variety of people. The main question it aims to answer is about how much insulin the body actually needs to maintain a normal blood sugar level. Participants will be asked to come in for a one-day study visit in which they will undergo a "graded insulin suppression test" ("GIST"). The GIST involves intravenous (into the vein) infusions of octreotide, a medication that turns off the body's own production of insulin, as well as replacement of insulin at two different levels (low and high), with or without replacement of glucagon, and glucose (sugar). The study investigators will check blood sugar levels every few minutes during the procedure to determine the effect of the two different insulin levels. This study will evaluate the GIST in both healthy volunteers and those at higher risk for type 2 diabetes.
Read the detailed description
This study aims to determine to what extent the hyperinsulinemia commonly associated with insulin resistance (IR) in those at risk for type 2 diabetes (T2D) is a primary phenomenon, rather than merely a secondary, compensatory response to IR. The hypothesis is that some people with obesity and hyperinsulinemia exhibit a primary, non-compensatory hyperinsulinemia that may foment IR and its dysmetabolic sequelae. If this were the case, lowering insulin levels should not result in a proportional rise in blood glucose as might be expected if the hyperinsulinemia truly were purely compensatory. This hypothesis has been difficult to prove, however, because of the tight feedback mechanism between blood glucose and insulin secretion; under normal circumstances insulin secretion declines only alongside blood glucose. As such, an attempt to lower insulin levels independently of blood glucose will raise blood glucose and trigger further insulin secretion, negating the purpose of the experiment. In order to circumvent this feedback regulation of glucose-stimulated insulin secretion, this study will adapt the existing insulin suppression test (IST) technique, which employs the somatostatin receptor ligand octreotide to suppress endogenous insulin secretion and then replaces insulin and dextrose exogenously as a measure of insulin action. In addition to employing the current standard hyperinsulinemic IST protocol to assess insulin sensitivity, this study will introduce a preceding, euinsulinemic step, in which insulin is lowered toward a healthy fasting serum insulin while assessing the resultant steady-state glucose, potentially with replacement of basal glucagon. The primary endpoints in this study are the steady-state plasma glucose and serum insulin levels during low- and high-dose insulin infusions meant to induce euinsulinemia and hyperinsulinemia, respectively. The study investigators will carefully monitor plasma glucose levels every 5-15 min, drawing from an indwelling peripheral IV catheter and performing the analysis using a dedicated bedside glucose analyzer. These glucose values will be used to detect and arrest any trends toward hypo or hyperglycemia and will also serve as the readout of the primary outcome - the euinsulinemic steady-state glucose (ESS-G) and hyperinsulinemic steady-state glucose (HSS-G). Serum insulin, C-peptide, and glucagon levels will be measured periodically during the procedure, but these results will not be available until several days later. The investigators will use these data to adjust the ESS-G and HSS-G data for differences in steady-state insulin levels by calculating the products of steady-state glucose and insulin: ESS-GxI and HSS-GxI. Finally, the investigators will assess the likelihood of primary hyperinsulinemia based on the GIST index: the ratio of the glucose x insulin product at euinsulinemic steady state relative to at baseline steady state (BSS), that is ESS-GxI / BSS-GxI.
- Conditions
- Insulin Resistance, Hyperinsulinemia, Obesity, Healthy
- Being tested
- Insulin regular, 2.0-3.2 mU/m2/min (euinsulinemia), Insulin regular, 32 mU/m2/min (hyperinsulinemia), Octreotide Acetate, 6-45 ng/kg/min, Dextrose 20 % in Water, Glucagon, 0-0.5 ng/kg/min
- Keywords
- Insulin resistance, Hyperinsulinemia, Type 2 diabetes, Obesity
- Medical subject headings
- Insulin Resistance, Hyperinsulinism, Obesity, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Insulin regular, 2.0-3.2 mU/m2/min (euinsulinemia)Drug
Insulin infusion to recapitulate euinsulinemia (normal basal insulin)
Insulin regular, 32 mU/m2/min (hyperinsulinemia)Drug
Insulin infusion to induce hyperinsulinemia for assessment of insulin sensitivity
Octreotide Acetate, 6-45 ng/kg/minDrug
Suppression of endogenous insulin secretion
Dextrose 20 % in WaterDrug
Production of steady-state plasma glucose (SSPG) reflective of insulin sensitivity at hyperinsulinemia
Glucagon, 0-0.5 ng/kg/minDrug
Replacement of endogenous glucagon suppressed by octreotide. (Use is optional at the PI's discretion.)
| Study group | Role | What they receive |
|---|---|---|
| Reference (healthy control) group | Experimental | Healthy volunteers with body mass index of 18-25 kg/m2, fasting serum insulin < 10 mU/L, hemoglobin A1c < 5.7%, and fasting plasma glucose < 100 mg/dL Receives: Drug: Insulin regular, 2.0-3.2 mU/m2/min (euinsulinemia); Drug: Insulin regular, 32 mU/m2/min (hyperinsulinemia); Drug: Octreotide Acetate, 6-45 ng/kg/min; Drug: Dextrose 20 % in Water; Drug: Glucagon, 0-0.5 ng/kg/min |
| Euinsulinemic group | Experimental | Volunteers with body mass index of 30-45 kg/m2, fasting serum insulin < 10 mU/L, hemoglobin A1c < 5.7%, and fasting plasma glucose < 100 mg/dL Receives: Drug: Insulin regular, 2.0-3.2 mU/m2/min (euinsulinemia); Drug: Insulin regular, 32 mU/m2/min (hyperinsulinemia); Drug: Octreotide Acetate, 6-45 ng/kg/min; Drug: Dextrose 20 % in Water; Drug: Glucagon, 0-0.5 ng/kg/min |
| Hyperinsulinemic group | Experimental | Volunteers with body mass index of 30-45 kg/m2, fasting serum insulin >= 13 mU/L, hemoglobin A1c < 5.7%, and fasting plasma glucose < 100 mg/dL Receives: Drug: Insulin regular, 2.0-3.2 mU/m2/min (euinsulinemia); Drug: Insulin regular, 32 mU/m2/min (hyperinsulinemia); Drug: Octreotide Acetate, 6-45 ng/kg/min; Drug: Dextrose 20 % in Water; Drug: Glucagon, 0-0.5 ng/kg/min |
What is being measured
The primary outcome is the main question the study is designed to answer.
Steady-state plasma glucose at euinsulinemia (ESS-G)
Plasma glucose level at steady state while insulin infusion rate is 2 mU/m2/min (units: mg/dL)
Measured: 150-180 minutes during GIST protocol
Steady-state plasma glucose at hyperinsulinemia (HSS-G)
Plasma glucose level at steady state while insulin infusion rate is 32 mU/m2/min and glucose infusion rate is 267 mg/m2/min, reflective of insulin sensitivity (units: mg/dL)
Measured: 270-300 minutes during GIST protocol
Secondary outcomes (3)
Product of steady-state glucose and insulin at euinsulinemia (ESS-G x I)
Product of plasma glucose and serum insulin levels while infusion rate is 2 mU/m2/min (units: mU/L x mg/dL)
Measured: 150-180 minutes during GIST protocol
Product of steady-state glucose and insulin at hyperinsulinemia (HSS-G x I)
Product of plasma glucose and serum insulin levels while infusion rate is 32 mU/m2/min (units: mU/L x mg/dL)
Measured: 270-300 minutes during GIST protocol
GIST index
Ratio of ESS-G x I to baseline steady state glucose x insulin product (BSS-G x I). Expect GIST index of approximately 1-2 in controls. GIST index below the control range suggests primary hyperinsulinemia, values within the control range for baseline-hyperinsulinemic subjects could be consistent either with mild insulin resistance or mixed primary + secondary hyperinsulinemia, and values above the control range are consistent with more significant insulin resistance (secondary hyperinsulinemia).
Measured: 150-180 minutes during GIST protocol
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start16 Sep 2024
- Primary completion13 Oct 2026
- Study completion13 Oct 2026
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.
- More trials run by Columbia UniversityThe 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
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pisa
- Responsible party
- Principal investigator, Joshua Cook, Columbia University
- Investigators
- Joshua R Cook, MD, PhD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06592261
- Sponsor's protocol ID
- AAAV2481
- Acronym
- GIST
- Status last verified
- Oct 2026
- First submitted
- 9 Sep 2024
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Participant-level clinical data will be preserved by depositing the deidentified data to Dryad, a generalist repository that is participating in the NIH Generalist Repository Ecosystem Initiative. The repository will provide metadata, persistent identifiers, and long-term access for open and controlled access. Each study created in Dryad is assigned a digital object identifier (DOI). This data DOI will be referenced in the publication to allow the research community easy access to the exact data used in the publication. To protect research participants' privacy and confidentiality, data submitted to the repository will not include personally identifiable information such as names or addresses. Additional protections, such as the approach for managing Health Insurance Portability and Accountability Act identifiers, will be used for de-identification and to provide a limited data set to minimize the risk of participant reidentification.
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Human Models of Selective Insulin Resistance: Graded Insulin Suppression Test (GIST) Pilot & Feasibility Study
- ClinicalTrials.gov ID
- NCT06592261
- Acronym / sponsor ID
- GIST / AAAV2481
- Conditions
- Insulin Resistance, Hyperinsulinemia, Obesity, Healthy
- Keywords
- Insulin resistance, Hyperinsulinemia, Type 2 diabetes, Obesity
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- University of Pisa
- Study start
- 16 Sep 2024 (actual)
- Primary completion
- 13 Oct 2026 (actual)
- Study completion
- 13 Oct 2026 (actual)
- First posted
- 19 Sep 2024 (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 goal of this study is to learn about how the hormone insulin controls blood sugar in a variety of people. The main question it aims to answer is about how much insulin the body actually needs to maintain a normal blood sugar level. Participants will be asked to come in for a one-day study visit in which they will undergo a "graded insulin suppression test" ("GIST"). The GIST involves intravenous (into the vein) infusions of octreotide, a medication that turns off the body's own production of insulin, as well as replacement of insulin at two different levels (low and high), with or without replacement of glucagon, and glucose (sugar). The study investigators will check blood sugar levels every few minutes during the procedure to determine the effect of the two different insulin levels. This study will evaluate the GIST in both healthy volunteers and those at higher risk for type 2 diabetes.
Detailed description
This study aims to determine to what extent the hyperinsulinemia commonly associated with insulin resistance (IR) in those at risk for type 2 diabetes (T2D) is a primary phenomenon, rather than merely a secondary, compensatory response to IR. The hypothesis is that some people with obesity and hyperinsulinemia exhibit a primary, non-compensatory hyperinsulinemia that may foment IR and its dysmetabolic sequelae. If this were the case, lowering insulin levels should not result in a proportional rise in blood glucose as might be expected if the hyperinsulinemia truly were purely compensatory. This hypothesis has been difficult to prove, however, because of the tight feedback mechanism between blood glucose and insulin secretion; under normal circumstances insulin secretion declines only alongside blood glucose. As such, an attempt to lower insulin levels independently of blood glucose will raise blood glucose and trigger further insulin secretion, negating the purpose of the experiment. In order to circumvent this feedback regulation of glucose-stimulated insulin secretion, this study will adapt the existing insulin suppression test (IST) technique, which employs the somatostatin receptor ligand octreotide to suppress endogenous insulin secretion and then replaces insulin and dextrose exogenously as a measure of insulin action. In addition to employing the current standard hyperinsulinemic IST protocol to assess insulin sensitivity, this study will introduce a preceding, euinsulinemic step, in which insulin is lowered toward a healthy fasting serum insulin while assessing the resultant steady-state glucose, potentially with replacement of basal glucagon. The primary endpoints in this study are the steady-state plasma glucose and serum insulin levels during low- and high-dose insulin infusions meant to induce euinsulinemia and hyperinsulinemia, respectively. The study investigators will carefully monitor plasma glucose levels every 5-15 min, drawing from an indwelling peripheral IV catheter and performing the analysis using a dedicated bedside glucose analyzer. These glucose values will be used to detect and arrest any trends toward hypo or hyperglycemia and will also serve as the readout of the primary outcome - the euinsulinemic steady-state glucose (ESS-G) and hyperinsulinemic steady-state glucose (HSS-G). Serum insulin, C-peptide, and glucagon levels will be measured periodically during the procedure, but these results will not be available until several days later. The investigators will use these data to adjust the ESS-G and HSS-G data for differences in steady-state insulin levels by calculating the products of steady-state glucose and insulin: ESS-GxI and HSS-GxI. Finally, the investigators will assess the likelihood of primary hyperinsulinemia based on the GIST index: the ratio of the glucose x insulin product at euinsulinemic steady state relative to at baseline steady state (BSS), that is ESS-GxI / BSS-GxI.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Reference (healthy control) group | Experimental | Drug: Insulin regular, 2.0-3.2 mU/m2/min (euinsulinemia), Drug: Insulin regular, 32 mU/m2/min (hyperinsulinemia), Drug: Octreotide Acetate, 6-45 ng/kg/min, Drug: Dextrose 20 % in Water, Drug: Glucagon, 0-0.5 ng/kg/minHealthy volunteers with body mass index of 18-25 kg/m2, fasting serum insulin < 10 mU/L, hemoglobin A1c < 5.7%, and fasting plasma glucose < 100 mg/dL |
| Euinsulinemic group | Experimental | Drug: Insulin regular, 2.0-3.2 mU/m2/min (euinsulinemia), Drug: Insulin regular, 32 mU/m2/min (hyperinsulinemia), Drug: Octreotide Acetate, 6-45 ng/kg/min, Drug: Dextrose 20 % in Water, Drug: Glucagon, 0-0.5 ng/kg/minVolunteers with body mass index of 30-45 kg/m2, fasting serum insulin < 10 mU/L, hemoglobin A1c < 5.7%, and fasting plasma glucose < 100 mg/dL |
| Hyperinsulinemic group | Experimental | Drug: Insulin regular, 2.0-3.2 mU/m2/min (euinsulinemia), Drug: Insulin regular, 32 mU/m2/min (hyperinsulinemia), Drug: Octreotide Acetate, 6-45 ng/kg/min, Drug: Dextrose 20 % in Water, Drug: Glucagon, 0-0.5 ng/kg/minVolunteers with body mass index of 30-45 kg/m2, fasting serum insulin >= 13 mU/L, hemoglobin A1c < 5.7%, and fasting plasma glucose < 100 mg/dL |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Body mass index of 18-25 and 30-45 kg/m2
- Able to understand written and spoken English and/or Spanish
- Fasting euinsulinemia (fasting serum insulin of 4-10 μU/mL) for reference group or hyperinsulinemia (fasting serum insulin ≥ 13 μU/mL) for hyperinsulinemic group on screening labs
- Written informed consent (in English or Spanish) and any locally required authorization (e.g., Health Insurance Portability and Accountability Act) obtained from the participant prior to performing any protocol-related procedures, including screening evaluations.
Key exclusion criteria (92 listed)
- Unable to provide informed consent in English or Spanish
- Unwillingness to use only bedpan or urinal to void or to refrain from non-emergent mobile device use during the GIST
- Documented weight loss of ≥ 5% of baseline within the previous 6 months
- Systolic blood pressure < 90 mm Hg or > 160 mm Hg, and/or
- Diastolic blood pressure < 60 mm Hg or > 100 mm Hg
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 |
|---|---|---|
| Insulin regular, 2.0-3.2 mU/m2/min (euinsulinemia)Insulin infusion to recapitulate euinsulinemia (normal basal insulin) | Drug | Euinsulinemic group, Hyperinsulinemic group, Reference (healthy control) group |
| Insulin regular, 32 mU/m2/min (hyperinsulinemia)Insulin infusion to induce hyperinsulinemia for assessment of insulin sensitivity | Drug | Euinsulinemic group, Hyperinsulinemic group, Reference (healthy control) group |
| Octreotide Acetate, 6-45 ng/kg/minSuppression of endogenous insulin secretion | Drug | Euinsulinemic group, Hyperinsulinemic group, Reference (healthy control) group |
| Dextrose 20 % in WaterProduction of steady-state plasma glucose (SSPG) reflective of insulin sensitivity at hyperinsulinemia | Drug | Euinsulinemic group, Hyperinsulinemic group, Reference (healthy control) group |
| Glucagon, 0-0.5 ng/kg/minReplacement of endogenous glucagon suppressed by octreotide. (Use is optional at the PI's discretion.) | Drug | Euinsulinemic group, Hyperinsulinemic group, Reference (healthy control) group |
Primary outcome
Steady-state plasma glucose at euinsulinemia (ESS-G)
Time frame: 150-180 minutes during GIST protocol
Plasma glucose level at steady state while insulin infusion rate is 2 mU/m2/min (units: mg/dL)
Steady-state plasma glucose at hyperinsulinemia (HSS-G)
Time frame: 270-300 minutes during GIST protocol
Plasma glucose level at steady state while insulin infusion rate is 32 mU/m2/min and glucose infusion rate is 267 mg/m2/min, reflective of insulin sensitivity (units: mg/dL)
3 secondary outcomes
Product of steady-state glucose and insulin at euinsulinemia (ESS-G x I)
Time frame: 150-180 minutes during GIST protocol
Product of steady-state glucose and insulin at hyperinsulinemia (HSS-G x I)
Time frame: 270-300 minutes during GIST protocol
GIST index
Time frame: 150-180 minutes during GIST protocol
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 16 Oct 2026.
- Individual participant dataSharing planned: Yes. Participant-level clinical data will be preserved by depositing the deidentified data to Dryad, a generalist repository that is participating in the NIH Generalist Repository Ecosystem Initiative. The repository will provide metadata, persistent identifiers, and long-term access for open and controlled access. Each study created in Dryad is assigned a digital object identifier (DOI). This data DOI will be referenced in the publication to allow the research community easy access to the exact data used in the publication. To protect research participants' privacy and confidentiality, data submitted to the repository will not include personally identifiable information such as names or addresses. Additional protections, such as the approach for managing Health Insurance Portability and Accountability Act identifiers, will be used for de-identification and to provide a limited data set to minimize the risk of participant reidentification.
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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.
Joshua R Cook, MD, PhD principal investigator
Columbia University
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 Insulin regular, 2.0-3.2 mU/m2/min (euinsulinemia), Insulin regular, 32 mU/m2/min (hyperinsulinemia) and Octreotide Acetate, 6-45 ng/kg/min in people with Insulin Resistance and Hyperinsulinemia, run by Columbia University 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 4 inclusion and 92 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 16 Oct 2026. 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. 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?
Steady-state plasma glucose at euinsulinemia (ESS-G) (time frame: 150-180 minutes during GIST protocol). The study lists 2 primary outcomes in all. 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 Oct 2026; AzTrials last refreshed its copy on 1 Nov 2026.