Human Models of Selective Insulin Resistance: Alpelisib, Part I

Summary

The goal of this clinical trial is to understand how the blood sugar-lowering hormone insulin works in healthy adults versus those who are at risk for type 2 diabetes. The study will use a drug called alpelisib, which interferes with insulin's actions in the body, to answer the study's main question: does the liver continue to respond to insulin's stimulation of fat production even when it loses the ability to stop making glucose (sugar) in response to insulin. Researchers will compare the impact of single doses of both alpelisib and placebo (inert non-drug) in random order (like flipping a coin) in study participants. Participants will be asked to stay twice overnight in the hospital, take single doses of alpelisib and placebo (one or the other on each of the two hospital stays), and receive intravenous (into the vein) infusions of non-radioactive "tracer" molecules that allow researchers to measure the production of glucose (sugar) and fats by the liver. Measurements will be done both overnight, while participants are asleep and fasting (not eating or drinking other than water) and while consuming a standardized diet of nutritional beverages during the following day.

The objective is to evaluate the effect of lowering insulin levels, while maintaining constant mild hyperglycemia, on plasma glucose and lipid levels.

Conditions

• Insulin Resistance
• Prediabetic State
• Overweight and Obesity
• Non-Alcoholic Fatty Liver Disease

Interventions

DRUG

Alpelisib 300 mg

All participants will ingest one dose of alpelisib 300 mg (2 x 150-mg overencapsulated tablets) on one of two study admissions.

DRUG

Placebo

All participants will ingest one dose of placebo (2 overencapuslated doses of microcrystalline cellulose) on one of two study admissions.

DRUG

[1-13C] sodium acetate

All participants will receive continuous infusions of \[1-13C\] sodium acetate for up to 23 hours on both study visits in order to quantify de novo lipogenesis (DNL). (non-experimental)

DRUG

[6,6-2H2] D-glucose

All participants will receive continuous infusions of \[6,6-2H2\] D-glucose for up to 15 hours on both study visits in order to quantify de novo lipogenesis (DNL). (non-experimental)

DIETARY_SUPPLEMENT

Nestlé BOOST Plus

All participants will ingest standardized mixed meals of Nestlé BOOST Plus on Study Day 1 and then smaller portions hourly x 8 hours on Study Day 2 of each study visit. (non-experimental)

Sponsors & Collaborators

• University of California, Berkeley

  collaborator OTHER

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  collaborator NIH

• Stanford University

  collaborator OTHER

• Columbia University

  lead OTHER

Principal Investigators

• Joshua R Cook, MD, PhD · Columbia University

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2024-04-24

Primary Completion

2026-12-31

Completion

2026-12-31

FDA Drug

Yes

Countries

• United States

Study Locations