Human Models of Selective Insulin Resistance: Alpelisib, Part I

Conditions

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

Eligibility Criteria

Sex

ALL

Age

18 Years - 70 Years

Healthy Volunteers

Accepted

Interventions

• Alpelisib 300 mg — DRUG
  All participants will ingest one dose of alpelisib 300 mg (2 x 150-mg overencapsulated tablets) on one of two study admissions.
• Placebo — DRUG
  All participants will ingest one dose of placebo (2 overencapuslated doses of microcrystalline cellulose) on one of two study admissions.
• [1-13C] sodium acetate — DRUG
  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)
• [6,6-2H2] D-glucose — DRUG
  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)
• Nestlé BOOST Plus — DIETARY_SUPPLEMENT
  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)

Study Details

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.

Key Dates

Start date

Apr 24, 2024

Status verified

Apr 2026

Primary completion

Dec 31, 2026

Completion

Dec 31, 2026

Study Design

Enrollment

32 participants (estimated)

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

BASIC_SCIENCE

Arms

• Experimental: Placebo then alpelisib (Insulin Sensitive group)
  On Study Visit 1, participants in the Insulin Sensitive (IS) group will undergo fasting and refed measurement of de novo lipogenesis (DNL) and endogenous glucose production (EGP) following a single dose of placebo. Then, 2-8 weeks later on Study Visit 2, participants will undergo measurement of DNL and EGP after a single dose of alpelisib 300 mg.
• Experimental: Alpelisib then placebo (Insulin Sensitive group)
  On Study Visit 1, participants in the Insulin Sensitive (IS) group will undergo fasting and refed measurement of de novo lipogenesis (DNL) and endogenous glucose production (EGP) following a single dose of alpelisib 300 mg. Then, 2-8 weeks later on Study Visit 2, participants will undergo measurement of DNL and EGP after a single dose of placebo.
• Experimental: Placebo then alpelisib (Insulin Resistant group)
  On Study Visit 1, participants in the Insulin Resistant (IR) group will undergo fasting and refed measurement of de novo lipogenesis (DNL) and endogenous glucose production (EGP) following a single dose of placebo. Then, 2-8 weeks later on Study Visit 2, participants will undergo measurement of DNL and EGP after a single dose of alpelisib 300 mg.
• Experimental: Alpelisib then placebo (Insulin Resistant group)
  On Study Visit 1, participants in the Insulin Resistant (IR) group will undergo fasting and refed measurement of de novo lipogenesis (DNL) and endogenous glucose production (EGP) following a single dose of alpelisib 300 mg. Then, 2-8 weeks later on Study Visit 2, participants will undergo measurement of DNL and EGP after a single dose of placebo.

Primary Outcome Measure

Hepatic de novo lipogenesis (DNL) (absolute value) [ Time Frame: Up to 24 hours after dosing ]

Central Contacts

• Joshua R Cook, MD, PhD
  2123056289
  [email protected]
• Ishwari Nagnur
  2123059336
  [email protected]

Locations (1)

Find similar trials in New York, NY

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