A Phase 1 interventional study of Insulin human and Octreotide Acetate in Insulin Resistance, Hyperinsulinemia and Metabolic Dysfunction Associated Steatotic Liver Disease, sponsored by Columbia University. Not yet recruiting at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-02-06.
Sponsored by Columbia University · Phase 1, Interventional, and Basic science
This is a single-center, prospective, randomized, controlled (crossover) clinical study designed to investigate the impact of lowering insulin levels on hepatic glucose production (HGP) vs de novo lipogenesis (DNL) in people with insulin resistance. The investigators will recruit participants with a history of overweight/obesity and evidence of insulin resistance (i.e., fasting hyperinsulinemia plus prediabetes and/or impaired fasting glucose and/or Homeostasis Model Assessment of Insulin Resistance [HOMA-IR] score >=2.73), and with evidence of metabolic dysfunction-associated steatotic liver disease (MASLD). Participants will undergo two pancreatic clamp procedures -- one in which serum insulin levels are maintained near hyperinsulinemic baseline (Maintenance Hyperinsulinemia or "MH" Protocol) and the other in which serum insulin levels are lowered by 50% (Reduction toward Euinsulinemia or "RE" Protocol). In both clamps the investigators will use stable-isotope tracers to monitor hepatic glucose and triglyceride metabolism. The primary outcome will be the impact of steady-state clamp insulinemia on HGP vs DNL.
Although high blood sugar and risk of heart disease are the most well-known health effects of type 2 diabetes (T2DM), metabolic dysfunction-associated steatotic liver disease (MASLD), in which too much fat accumulates in the liver, has come to be recognized as another important complication. Unchecked, MASLD can progress to severe liver inflammation, liver failure, and even liver cancer. The investigators suspect that high levels of the blood sugar-lowering hormone insulin leads to excessive fat production by the liver, and so lowering insulin levels might help to improve MASLD. In order to answer this question, the investigators will recruit people with MASLD at risk for T2DM to perform a "pancreatic clamp" - a procedure in which the body's production of insulin is temporarily shut off and then replaced at the same or lower levels. Again, the investigators expect that lowering insulin levels will lower fat production ("de novo lipogenesis" or DNL). Research participants in this prospective, randomized, controlled (crossover) study will therefore undergo two pancreatic clamps in random order: one roughly maintaining their own internal ("basal") insulin level ("MH Protocol") and one in which the investigators lower that basal insulin level by 50% ("RE Protocol"). In each case, the investigators will observe the absolute and relative changes in the liver's production of glucose (hepatic glucose production, HGP) and of triglycerides (de novo lipogenesis, DNL) using stable-isotope tracers.
2,969 studies on the registry are indexed under Insulin Resistance; 338 are open to participants now.
This study's planned enrollment of 36 is close to the median of 40 across 2,369 interventional studies indexed under Insulin Resistance.
Browse Insulin Resistance studies →Columbia University is the lead sponsor of 1,136 studies on the registry; 195 are open to participants now.
Of its 180 completed or terminated interventional studies of FDA-regulated products, 148 (82%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Evidence of insulin resistance, represented by any or all of the following criteria:
Meeting either of the American Diabetes Association's definitions for prediabetes or Impaired fasting glucose (IFG) within the previous year and on screening labs:
Exclusion Criteria:
Abnormal blood pressure (including on treatment, if prescribed)
Abnormal resting heart rate: \< 60 or ≥ 110 bpm
Laboratory evidence of diabetes mellitus:
Liver function abnormalities (either of the following)
Abnormal complete blood count (CBC) (any of the following)
History of having met any of the American Diabetes Association's definitions of diabetes mellitus (i.e., overt diabetes):
Use of most antidiabetic medications within the 30 days prior to screening
Use of certain lipid-lowering drugs within 30 d prior to screening visit:
Known, documented history, at the time of screening, of any of the following medical conditions:
Use of certain medications currently or within 30 d prior to screening:
History of certain weight-loss (bariatric) surgery, including:
Positive urine drug screen, with exceptions for:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
On Pancreatic Clamp Visit 1 (MH Protocol), the insulin infusion rate (IIR) will be set to approximately replicate participants' endogenous fasting serum insulin levels based on screening visit data for the duration of the pancreatic clamp. On Pancreatic Clamp Visit 2 (RE Protocol), the IIR will be set to reduce serum insulin levels to roughly 50% of the screening fasting serum insulin for the duration of the pancreatic clamp. In both cases, plasma glucose will be clamped to approximately 140 mg/dL +/- 10%.
Drug: Insulin human · Drug: Octreotide Acetate · Drug: Glucagon · Drug: Growth Hormone, Human · Drug: 20% D-glucose (aq) · Diagnostic Test: [6,6-2H2] D-glucose · Diagnostic Test: [1-13C1] sodium acetate · Dietary Supplement: Nestle BOOST Plus · Dietary Supplement: KIND Bar · Device: Harvard Apparatus PHD ULTRA CP syringe pump · Device: Yellow Springs Instruments (YSI) 2500 Biochemistry Glucose/Lactate Analyzer
On Pancreatic Clamp Visit 1 (RE Protocol), the insulin infusion rate (IIR) will be set to produce serum insulin levels of approximately 50% that of the screening fasting serum insulin level for the full duration of the pancreatic clamp. On Pancreatic Clamp Visit 2 (MH Protocol), the IIR will be set to approximately replicate the full fasting serum insulin for the duration of the pancreatic clamp. In both cases, plasma glucose will be clamped to approximately 140 mg/dL +/- 10%.
Drug: Insulin human · Drug: Octreotide Acetate · Drug: Glucagon · Drug: Growth Hormone, Human · Drug: 20% D-glucose (aq) · Diagnostic Test: [6,6-2H2] D-glucose · Diagnostic Test: [1-13C1] sodium acetate · Dietary Supplement: Nestle BOOST Plus · Dietary Supplement: KIND Bar · Device: Harvard Apparatus PHD ULTRA CP syringe pump · Device: Yellow Springs Instruments (YSI) 2500 Biochemistry Glucose/Lactate Analyzer
Insulin infusion rate (IIR) will be determined either to maintain fasting serum insulin levels (MH protocol) or to reduce fasting serum insulin levels by approximately 50% toward euinsulinemia (RE protocol).
Also known as: Novolin-R, Humulin-R
Octreotide will be infused at 30 ng/kg/min to suppress endogenous insulin, glucagon, and growth hormone secretion. Co-administered with glucagon and rhGH.
Glucagon will be replaced at a constant rate of up to 0.65 ng/kg/min to maintain baseline counterregulatory response. Co-administered with octreotide and rhGH.
Recombinant human growth hormone (rhGH) will be replaced at a constant rate of up to 3 ng/kg/min to maintain baseline counterregulatory response. Co-administered with octreotide and glucagon.
Also known as: Omnitrope, Zomacton
20% D-glucose (aq) (D20W) will be administered to counteract hypoglycemia or strongly downward blood glucose trends, as needed.
Also known as: D20W
Stable isotope tracer administered to calculate glucose kinetics during pancreatic clamp.
Also known as: D2-glucose, D2G
Stable isotope tracer administered to calculate de novo lipogenesis during pancreatic clamp.
Also known as: 13C-acetate, C13A
Nutritional supplement will be administered to provide standardized "mixed meals" prior to the pancreatic clamp.
Energy bar snack will be administered the evening before the pancreatic clamp.
Syringe pump used for highly precise administration of insulin, octreotide/glucagon/rhGH, and D20W (as needed) even at low infusion rates.
Glucose oxidase analyzer used to detect plasma glucose levels at the point of care. YSI have been the gold standard in clamp studies for many years. Two machines will run in parallel to ensure accuracy of results.
Hepatic de novo lipogenesis (DNL) (absolute value)
Percent incorporation of newly synthesized fatty acids into plasma or very low-density lipoprotein (VLDL) triglyceride (TG) during pancreatic clamp procedures. (Unit: %)
Time frame: Up to 6.5 hours of pancreatic clamp protocol
Hepatic de novo lipogenesis (DNL) (relative value)
Percent incorporation of newly synthesized fatty acids into plasma or VLDL TG during pancreatic clamp procedures. (Unit: fold difference and/or ∆% versus other group)
Time frame: Up to 6.5 hours of pancreatic clamp protocol
Endogenous glucose production (EGP) (absolute value)
Calculated from D2G tracer enrichment by the Steele equations during pancreatic clamp procedures. (Units: mg/kg/min)
Time frame: Up to 6.5 hours of pancreatic clamp protocol
Endogenous glucose production (EGP) (relative value)
Calculated from D2G tracer enrichment by the Steele equations during pancreatic clamp procedures. (Units: fold difference and/or ∆% versus other group)
Time frame: Up to 6.5 hours of pancreatic clamp protocol
Plasma glucose level
Plasma glucose level during pancreatic clamp procedures. (Units: mg/dL)
Time frame: Up to 6.5 hours of pancreatic clamp protocol
Serum insulin level
Serum insulin level during pancreatic clamp procedures (Units: µU/mL)
Time frame: Up to 6.5 hours of pancreatic clamp protocol
Serum or plasma triglyceride level
Serum or plasma triglyceride level in response to pancreatic clamp procedures (Units: mg/dL)
Time frame: Up to 6.5 hours of pancreatic clamp protocol
Plasma free fatty acids level
Plasma free fatty acids level in response to pancreatic clamp procedures. (Units: mmol/L)
Time frame: Up to 6.5 hours of pancreatic clamp protocol
Glucose kinetics: rate of appearance (absolute value)
Calculated from D2G tracer enrichment by the Steele equations during pancreatic clamp procedures. (Units: mg/kg/min)
Time frame: Up to 6.5 hours of pancreatic clamp protocol
Glucose kinetics: rate of appearance (relative value)
Calculated from D2G tracer enrichment by the Steele equations during pancreatic clamp procedures. (Units: fold difference and/or ∆% versus other group)
Time frame: Up to 6.5 hours of pancreatic clamp protocol
Glucose kinetics: rate of disappearance (absolute value)
Calculated from D2G tracer enrichment by the Steele equations during pancreatic clamp procedures. (Units: mg/kg/min)
Time frame: Up to 6.5 hours of pancreatic clamp protocol
Glucose kinetics: rate of disappearance (relative value)
Calculated from D2G tracer enrichment by the Steele equations during pancreatic clamp procedures. (Units: fold difference and/or ∆% versus other group)
Time frame: Up to 6.5 hours of pancreatic clamp protocol
Serum C-peptide level
Serum C-peptide level in response to octreotide infusion during pancreatic clamps. (Units: ng/mL)
Time frame: Up to 6.5 hours of pancreatic clamp protocol
Plasma glucagon level
Plasma glucagon level in response to octreotide infusion during pancreatic clamps. (Units: ng/L)
Time frame: Up to 6.5 hours of pancreatic clamp protocol
Serum growth hormone level
Serum growth hormone level in response to octreotide infusion during pancreatic clamps. (Units: ng/mL)
Time frame: Up to 6.5 hours of pancreatic clamp protocol
Plan to share: 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.
Time frame: Scientific data will be shared as soon as possible. Scientific data included in published manuscripts will be available at the time of publication; all other generated scientific data will be shared no later than the end of the award. The study data will be stored in the repository for at least 5 years.
Access criteria: To request access of the data, researchers will use the standard processes at Dryad. Given that we seek the widest possible availability, in most cases all that is necessary is obtaining a Dryad account from the repository web site.
No publications or documents are linked to this record.
Start is estimated for Jan 2027; primary completion for Dec 2028, 23 months later.
Of 51 non-industry phase 1 interventional studies under Insulin Resistance, half reached primary completion within 26 months of starting (the median), counting those still running; a quarter within 14 and three quarters within 80. This study's planned 23 months is below that.
Counting every sponsor, half of 65 studies reached it within 24 months; a quarter within 13 and three quarters within 67.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Feb 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Insulin, Regular, Human · Octreotide · Glucagon · Human Growth Hormone · Glucose