Human Models of Selective Insulin Resistance: Pancreatic Clamp

Starting soon · Phase 1

Conditions studied: Insulin Resistance, Hyperinsulinemia, Metabolic Dysfunction Associated Steatotic Liver Disease, Non-Alcoholic Fatty Liver Disease, Prediabetic State, Obesity

In brief

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.

Key facts

Study ID

NCT06558422

Run by

Columbia University

People needed

36

Starts

2027-01-01

Expected to finish

2029-02-28

Last updated by the study team

2026-02-06

Who can join

Age: 18 and older, up to 65. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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:
• Prediabetes: Hemoglobin A1c 5.7-6.4%
• IFG: plasma glucose of 100-125 mg/dL after 8-h fast
• 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.

You may not qualify if…

• 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):

Where it is running

• Columbia University Irving Medical Center — New York, New York, United States

Full record on ClinicalTrials.gov

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