Human Models of Selective Insulin Resistance: Alpelisib, Part I

Status: Recruiting
Location: See location...
Intervention Type: Dietary supplement, Drug
Study Type: Interventional
Study Phase: Phase 1
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 70
Healthy Volunteers: t
View:

• Adults aged 18-70 years, using highly effective contraception if of childbearing potential

• Able to understand written and spoken English and/or Spanish

• Body mass index of:

‣ For Group IS: BMI 18-25 kg/m2

⁃ For Group IR: BMI 30-45 kg/m2

• Evidence of insulin sensitivity or insulin resistance:

‣ Insulin sensitive (for Group IS) defined as all of the following: (1) Fasting serum insulin ≤ 10 µIU/mL, (2) Absence of dysglycemia (fasting plasma glucose \< 100 mg/dL and hemoglobin A1c \< 5.7%), (3) Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) score \< 2.5, and (4) Fibrosis-4 (FIB-4) score \< 1.3

⁃ Insulin resistant (for Group IR) defined as fasting serum insulin ≥ 13 µIU/mL plus at least one of the following: (1) Presence of prediabetic state (fasting plasma glucose 100-125 mg/dL and/or hemoglobin A1c 5.7-6.4%), and/or HOMA-IR ≥ 2.5

Locations
United States
New York
Columbia University Irving Medical Center
RECRUITING
New York
Contact Information
Primary
Joshua R Cook, MD, PhD
jrc2175@cumc.columbia.edu
2123056289
Backup
Zachary D Sone
zds2120@cumc.columbia.edu
2123059336
Time Frame
Start Date: 2024-04-24
Estimated Completion Date: 2026-12
Participants
Target number of participants: 32
Treatments
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.
Sponsors
Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of California, Berkeley, Stanford University
Leads: Columbia University

This content was sourced from clinicaltrials.gov