Alpelisib Challenge Test (ACT)

ConditionsInsulin Resistance Type 2 Diabetes Obesity & Overweight Healthy Adult Participants

Trial statusRecruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

Age18-70

SponsorColumbia University

About this trial

The goal of this study is to test a potentially easier method for measuring how much insulin a person is capable of producing than the current gold-standard method, the "hyperglycemic clamp." Participants will come in for a two-day (overnight) visit in which they will first undergo a "hyperglycemic clamp," in which they receive an intravenous (into the vein) infusion of glucose (sugar) in order to measure the maximum amount of insulin their body produces in response. They will then consume a series of three standardized meals throughout the rest of the day. At 23:00, they will take a single dose of alpelisib, a drug that interferes within insulin's actions in the body. Then, the following morning, they will undergo a "Mixed Meal Tolerance Test" in which they consume a standardized liquid nutritional beverage and have blood drawn periodically before and during the test.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Adults aged 18-70 years

Able to understand wrifen and spoken English and/or Spanish

Body mass index of 18-45 kg/m2 (or 18-42 kg/m2 for those of Asian ancestry)

For Lean group: BMI 18.0-24.9 kg/m2 (or 18.0-22.9 kg/m2 for those of Asian ancestry)

Disqualifiers

Inability to provide informed consent in English or Spanish

Unwillingness to fast (except water) for up to 18 hours

Unwillingness not to get out of bed and to use bedpan/urinal to void for up to 15 hours

Documented weight change of ≥ 5.0% of baseline within the previous 3 months

Trial design

Design model

Parallel

Treatments tested in this trial

Alpelisib 300 mg
Drug
All participants will ingest one dose of alpelisib 300 mg (2 x 150-mg tablets) at 23:00 on Study Day 1
Alpelisib Challenge Test (ACT): Mixed Meal Tolerance Test (MMTT) after taking alpelisib
Diagnostic test
All participants will ingest standardized mixed meals of Nestlé BOOST Plus on the morning of Study Day 2 after taking alpelisib the previous evening
Hyperglycemic clamp
Diagnostic test
All participants will undergo a two-hour hyperglycemic clamp procedure to measure pancreatic insulin reserve on the morning of Study Day 1, prior to taking alpelisib. This procedure involves an infusion of dextrose 20% solution.

Treatment groups

15 Participants

are divided into 3 treatment groups

Group A: Lean (healthy control) groupExperimental treatment 3 interventions

Group B: Overweight groupExperimental treatment 3 interventions

Group C: Obesity groupExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

Correlation coefficient between clamp and ACT/MMTT

Determination of utility of Alpelisib Challenge Test as measure of pancreatic beta-cell reserve based on correlation of insulin/C-peptide levels and/or insulin secretion rates during MMTT portion of ACT versus gold-standard hyperglycemic clamp

Time frame

Up to 17 hours after dosing alpelisib

Secondary outcomes

Serum insulin level

Serum insulin levels during steady-state period of hyperglycemic clamp and in response to alpelisib following an overnight fast and MMTT

Time frame