Pancreatic Clamp in NAFLD

Obesity Clinical Trial

Official title: Role of Hyperinsulinemia in Non-Alcoholic Fatty Liver Disease (NAFLD) Pathogenesis: Pancreatic Clamp Pilot & Feasibility Study

Status Recruiting

Clinical Trial Summary

This is a single-center, prospective, randomized, controlled (crossover) clinical study designed to investigate the specific dose-response impact of insulin infusion rate (IIR) on blood glucose levels during a pancreatic clamp study. 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, or clinically judged to be at high risk for, uncomplicated non-alcoholic fatty liver disease (NAFLD). Participants will undergo two pancreatic clamp procedures in which individualized basal IIR are identified, followed in one by maintenance of basal IIR (maintenance hyperinsulinemia, MH) and in the other by a stepped decline in IIR (reduction toward euinsulinemia, RE). In both clamps the investigators will closely monitor plasma glucose and various metabolic parameters. The primary outcome will be the absolute and relative changes in steady-state plasma glucose levels at each stepped decline in IIR.

Clinical Trial Description

Although high blood sugar and risk of heart disease are the most well-known health effects of type 2 diabetes (T2DM), nonalcoholic fatty liver disease (NAFLD), in which too much fat accumulates in the liver, has come to be recognized as another important complication. Unchecked, NAFLD 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 NAFLD. In order to answer this question, the investigators will recruit people at risk for T2DM and NAFLD 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. Because this is a new research approach, the investigators first need to understand how lowering insulin levels affects blood sugar. Research participants in this pilot study will therefore undergo two pancreatic clamps in random order: one roughly maintaining their own internal ("basal") insulin level and one in which the investigators lower that basal insulin level by up to 40%. In each case, the investigators will observe the absolute and relative changes in blood sugar and the levels of certain fats as the investigators change the insulin level. Once the investigators have found a lower insulin level that they can safely maintain, the investigators will go on to study its effect on fat production in a later study. ;

Related Conditions & MeSH terms

• Fatty Liver
• Hyperinsulinemia
• Hyperinsulinism
• Insulin Resistance
• Liver Diseases
• Non-alcoholic Fatty Liver Disease
• Obesity
• Prediabetic State

• NCT number: NCT05724134
• Study type: Interventional
• Source: Columbia University
• Contact: Zachary Sone
• Phone: 2123059336
• Email: zds2120@cumc.columbia.edu
• Status: Recruiting
• Phase: Phase 1
• Start date: August 29, 2023
• Completion date: January 2025