Alpelisib Challenge Test (ACT)

NCT07778524 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: ACYY1444K23DK140614
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Insulin Resistance; Type 2 Diabetes; Obesity & Overweight; Healthy Adult Participants

Keywords

Insulin resistance; Type 2 diabetes; Hyperinsulinemia; Obesity; Overweight; Healthy volunteers

Outcome Measures

Primary Outcomes (1)

• 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

  Up to 17 hours after dosing alpelisib

Secondary Outcomes (4)

• Serum insulin level

  After 2-3 hours of hyperglycemic clamp and up to 17 hours after alpelisib dose

• Serum C-peptide level

  After 2-3 hours of hyperglycemic clamp and up to 17 hours after alpelisib dose

• Insulin secretion rate (ISR)

  After 2-3 hours of hyperglycemic clamp and up to 17 hours after alpelisib dose

• Insulin clearance rate (ICR)

  After 2-3 hours of hyperglycemic clamp and up to 17 hours after alpelisib dose

Other Outcomes (2)

• Plasma glucose level

  After 2-3 hours of hyperglycemic clamp and up to 17 hours after alpelisib dose

• Plasma alpelisib level

  10 hours after alpelisib dose

Study Arms (3)

Lean (healthy control) group

EXPERIMENTAL

Healthy volunteers with body mass index of 18.0-24.9 kg/m2, hemoglobin A1c \< 6.5%, and fasting plasma glucose \< 126 mg/dL

Drug: Alpelisib 300 mg; Diagnostic Test: Alpelisib Challenge Test (ACT): Mixed Meal Tolerance Test (MMTT) after taking alpelisib; Diagnostic Test: Hyperglycemic clamp

Overweight group

EXPERIMENTAL

Volunteers with body mass index of 25.0-29.9 kg/m2, hemoglobin A1c \< 6.5%, and fasting plasma glucose \< 126 mg/dL

Drug: Alpelisib 300 mg; Diagnostic Test: Alpelisib Challenge Test (ACT): Mixed Meal Tolerance Test (MMTT) after taking alpelisib; Diagnostic Test: Hyperglycemic clamp

Obesity group

EXPERIMENTAL

Volunteers with body mass index of 30.0-45.0 kg/m2, hemoglobin A1c \< 6.5%, and fasting plasma glucose \< 126 mg/dL

Drug: Alpelisib 300 mg; Diagnostic Test: Alpelisib Challenge Test (ACT): Mixed Meal Tolerance Test (MMTT) after taking alpelisib; Diagnostic Test: Hyperglycemic clamp

Interventions

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

Also known as: Piqray

Lean (healthy control) group; Obesity group; Overweight group

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.

Lean (healthy control) group; Obesity group; Overweight group

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

Lean (healthy control) group; Obesity group; Overweight group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• For Overweight group: BMI 25.0-29.9 kg/m2 (or 23.0-27.4 kg/m2 for those of Asian ancestry)
• For Obesity group: BMI 30.0-45.0 kg/m2 (or 27.5-42 kg/m2 for those of Asian ancestry)

You may not qualify if:

• 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
• Abnormal blood pressure
• Systolic blood pressure \< 90 mm Hg or \> 160 mm Hg, and/or
• Diastolic blood pressure \< 55 mm Hg or \> 100 mm Hg
• Abnormal resting heart rate \< 55 bpm or ≥ 110 bpm
• Sinus tachycardia that has been extensively worked up and considered benign by the recruit's personal physician may be permitted at the PI's discretion
• Sinus bradycardia between heart rates of 45 and 54 bpm may be permitted at the PI's discretion if in a clinically appropriate setting (e.g., toned athlete, taking beta blockers)
• Abnormal (i.e., non-regular) heart rhythm detected on physical exam
• Abnormal screening serum electrolytes judged by the PI to be potentially clinically significant
• Liver function abnormalities (either of the following)
• Transaminases (AST or ALT) \> 3.0 x the upper limit of normal
• Total bilirubin \> 1.25 x the upper limit of normal

Sponsors & Collaborators

• Columbia University: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• University of Pisa: collaborator

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Insulin Resistance; Diabetes Mellitus, Type 2; Obesity; Overweight; Hyperinsulinism

Interventions

Alpelisib

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Joshua R Cook, MD, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joshua R Cook, MD, PhD

CONTACT

2123052663; jrc2175@cumc.columbia.edu

Ishwari Nagnur

CONTACT

2123059336; imn2113@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: August 18, 2026
• First Posted: August 21, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2028
• Last Updated: August 21, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Will be available within 1 year of study completion and will be available indefinitely
• Access Criteria: Public access allowed

Locations

US (1)