Study on Insulin Levels and Liver Fat in Insulin Resistance
This study is investigating how lowering insulin levels might affect fat production in the liver for people with insulin resistance and metabolic dysfunction-associated steatotic liver disease (MASLD). Researchers believe high insulin levels might lead to too much fat in the liver. You may be able to join if you are 18-65 years old, have a BMI between 27-50, and show signs of insulin resistance, such as prediabetes or impaired fasting glucose. The study will use a "pancreatic clamp" procedure, where your body's own insulin production is temporarily stopped and then replaced with either your usual insulin level or a lower level using Insulin human, Octreotide Acetate, Glucagon, and Growth Hormone, Human. Success would mean seeing a reduction in liver fat production (hepatic de novo lipogenesis) and improved glucose production.
- Study design
- This is a single-center, prospective, randomized, controlled (crossover) study with 36 planned participants. It compares two different insulin level protocols in the same individuals.
- What's involved
- You would undergo two "pancreatic clamp" procedures, each lasting up to 6.5 hours. These procedures involve infusions of various medications and monitoring.
- Compensation
- Not stated in the trial record.
- Follow-up
- The primary measurements for this study are taken up to 6.5 hours during the pancreatic clamp protocol.
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NCT06558422
Human Models of Selective Insulin Resistance: Pancreatic Clamp
Not Yet Recruiting
PHASE1Ages 18–65InterventionalBasic scienceColumbia UniversityInvestigator-initiated
~36 participants
Updated 2026-02-06 on ClinicalTrials.gov
What's tested:Insulin humanOctreotide AcetateGlucagonGrowth Hormone, Human20% D-glucose (aq)[6,6-2H2] D-glucose
At a glance
Recruiting sites
0 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Hepatic de novo lipogenesis (DNL) (absolute value)
Measured over Up to 6.5 hours of pancreatic clamp protocol
+5 more outcomes measured
Conditions
Where it's being run
1 sites across 1 statesNew York1
Study leadership
- Joshua R Cook, MD, PhD · PRINCIPAL_INVESTIGATOR · Columbia University
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Men and women, ages 18-65 years
Body mass index of 27-50 kg/m2
Able to understand written and spoken English and/or Spanish
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:
Homeostasis Model of Insulin Resistance (HOMA-IR) score ≥ 2.73
Fasting hyperinsulinemia (fasting insulin level ≥ 13 µU/mL) on screening labs
Presence of uncomplicated MASLD, defined by vibration-controlled transient elastography (VCTE) as a steatosis score S1-S3 + fibrosis score F0-F2
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.
Clinical concern for absolute insulin deficiency (e.g., type 1 diabetes, pancreatic disease)
Known diagnoses of familial combined hyperlipidemia or familial chylomicronemia syndrome
Use of certain lipid-lowering drugs within 30 d prior to screening visit:
Fibrates (e.g., fenofibrate, clofibrate, gemfibrozil)
Prescription-strength omega-3 fatty acids (e.g., Lovaza®, Vascepa®)
Known, documented history, at the time of screening, of any of the following medical conditions:
Pancreatic pathology
Cardiovascular diseases (N.B. uncomplicated hypertension is not exclusionary)
Chronic kidney disease, Stage 3 or higher (estimated glomerular filtration rate \< 60 mL min-1 1.73 m-2), of any cause
Advanced or severe liver disease (including fibrosis scores of F3-F4 on screening VCTE)
Gallstone disease
Chronic viral illness
Malabsorptive conditions (active)
Active seizure disorder (including controlled with antiepileptic drugs)
Psychiatric diseases causing functional impairment and/or requiring use of anti-dopaminergic antipsychotic drugs associated with significant weight gain/metabolic dysfunction (e.g., clozapine, olanzapine), monoamine oxidase inhibitors, tricyclic antidepressants, or lithium
Known adrenal disease
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 (see above)
Active malignancy, or hormonally active benign neoplasm
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 certain medications currently or within 30 d prior to screening:
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 (angiotensin-converting enzyme inhibitor) / ARB (angiotensin receptor blocker) used for uncomplicated hypertension rather than for congestive heart failure, etc. Note, as above, that antidiabetic drugs except metformin within 30 days of screening are excluded.
Loop diuretics (furosemide, torsemide, ethacrynic acid)
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
Fludrocortisone
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.
Positive urine drug screen, with exceptions for:
Lawfully prescribed medications
Marijuana/THC positivity, provided that the participant agrees not to use it during the same period that they will abstain from alcohol
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 (including soy, dairy, peanuts, tree nuts, or egg), 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.
Exclusion
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 clamp
Documented weight loss of ≥ 5% of baseline within the previous 3 months
Abnormal blood pressure (including on treatment, if prescribed)
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
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 days)
Laboratory evidence of diabetes mellitus:
Hemoglobin A1c ≥ 6.5%, and/or
Fasting plasma glucose ≥ 126 mg/dL
Positive qualitative β-hCG (Human chorionic gonadotropin, β subunit) (i.e., pregnancy test) in women of childbearing potential
Positive urine drug screen, except for lawfully prescribed medications and/or marijuana
Liver function abnormalities (either of the following)
Transaminases (AST or ALT) \> 3.0 x the upper limit of normal
Total bilirubin \> 1.25 x the upper limit of normal
Fasting serum triglycerides at screening ≥ 400 mg/dL
Abnormal screening serum electrolytes that are considered potentially significant according to the clinical judgment of the PI
Abnormal complete blood count (CBC) (any of the following)
Hemoglobin \< 10 g/dL or hematocrit \< 30%
Platelet count \< 100,000/µL
Women currently pregnant, measured by serum and/or urine β-hCG, or trying to become pregnant
Women currently breastfeeding
History of having met any of the American Diabetes Association's definitions of diabetes mellitus (i.e., overt diabetes):
Hemoglobin A1c ≥ 6.5%, or rapid rise in documented HbA1c values causing clinical concern for evolving insulin deficiency
Plasma glucose ≥ 126 mg/dL after 8-h fast
Plasma glucose of ≥ 200 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
What this trial measures
- Hepatic de novo lipogenesis (DNL) (absolute value)Up to 6.5 hours of pancreatic clamp protocol
Percent incorporation of newly synthesized fatty acids into plasma or very low-density lipoprotein (VLDL) triglyceride (TG) during pancreatic clamp procedures. (Unit: %)
- Hepatic de novo lipogenesis (DNL) (relative value)Up to 6.5 hours of pancreatic clamp protocol
Percent incorporation of newly synthesized fatty acids into plasma or VLDL TG during pancreatic clamp procedures. (Unit: fold difference and/or ∆% versus other group)
- Endogenous glucose production (EGP) (absolute value)Up to 6.5 hours of pancreatic clamp protocol
Calculated from D2G tracer enrichment by the Steele equations during pancreatic clamp procedures. (Units: mg/kg/min)
- Endogenous glucose production (EGP) (relative value)Up to 6.5 hours of pancreatic clamp protocol
Calculated from D2G tracer enrichment by the Steele equations during pancreatic clamp procedures. (Units: fold difference and/or ∆% versus other group)
- Plasma glucose levelUp to 6.5 hours of pancreatic clamp protocol
Plasma glucose level during pancreatic clamp procedures. (Units: mg/dL)
- Serum insulin levelUp to 6.5 hours of pancreatic clamp protocol
Serum insulin level during pancreatic clamp procedures (Units: µU/mL)