Insulin Management for Non-alcoholic Fatty Liver Disease

Palo Alto (17 mi)

Overseen byJoshua R Cook, MD, PhD

Age: 18+

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Columbia University

No Placebo Group

Approved in 5 jurisdictions

Trial Summary

What is the purpose of this trial?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.

Eligibility Criteria

This trial is for people who are overweight or obese, have insulin resistance (evidenced by high fasting insulin levels, prediabetes/impaired fasting glucose, or a HOMA-IR score of at least 2.73), and either have non-alcoholic fatty liver disease (NAFLD) or are at high risk for it.

Inclusion Criteria

I am between 18 and 65 years old.

I am diagnosed with or at high risk for a type of liver disease related to metabolic dysfunction.

Exclusion Criteria

I am unwilling to use only a bedpan or urinal during certain procedures.

I am not pregnant or at risk of becoming pregnant.

My liver isn't working properly.

I can provide informed consent in English or Spanish.

I have lost 5% or more of my original weight in the last 3 months.

I have not had a severe infection or ongoing fever.

My drug test was positive, but only for prescribed medications.

I have had weight-loss surgery in the past.

I have had diabetes or diabetes during pregnancy.

I might have a complete lack of insulin.

I have been diagnosed with a specific type of high cholesterol.

Treatment Details

The study tests how lowering insulin affects liver glucose production versus fat creation in the liver. Participants will undergo two procedures with different insulin levels while their liver metabolism is monitored using special tracers.

2Treatment groups

Experimental Treatment

Group I: Reduction toward euinsulinemia (RE) protocolExperimental Treatment11 Interventions

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%.

Group II: Maintenance hyperinsulinemia (MH) Protocol then Reduction toward Euinsulinemia (RE) ProtocolExperimental Treatment11 Interventions

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%.

Insulin human is already approved in European Union, United States, Canada, Japan, China for the following indications:

🇪🇺 Approved in European Union as Humulin for: