- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05733455
Effect of Alpelisib in Healthy Volunteers
Insulin Resistance in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: Alpelisib Pilot & Feasibility Study
The goal of this clinical trial is to test a single dose of the phosphoinositide-3-kinase (PI3K) inhibitor alpelisib versus placebo in healthy volunteers. The main questions it aims to answer are the impact of acute alpelisib-induced insulin resistance on parameters of glucose and lipid metabolism (how healthy people respond to temporary insulin resistance so that the investigators can see what happens to how the liver handles fat and sugar).
Participants will:
- Consume their total calculated daily caloric needs in nutritional supplements, divided in three meals, and otherwise fast for 24 hours
- Take a dose of alpelisib 300 mg or placebo at bedtime
- Wear a continuous glucose monitor for 72 hours
- Participate in an oral glucose tolerance test (OGTT)
Researchers will compare blood tests before and during OGTT in participants randomized (like the flip of a coin) to alpelisib versus placebo to see how the drug treatment affects plasma glucose, serum insulin, and serum lipid parameters (triglycerides, free fatty acids, and apolipoprotein B).
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Zachary Sone
- Phone Number: 212-305-9336
- Email: zds2120@cumc.columbia.edu
Study Locations
-
-
New York
-
New York, New York, United States, 10032
- Columbia University Irving Medical Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Adults aged 18-65 years, using highly effective contraception if of childbearing potential
- Able to understand written and spoken English and/or Spanish
- Body mass index of 18.0-26.9 kg/m2
- Healthy, as determined by screening assessments and Principal Investigator's (PI's) clinical/scientific judgment. "Healthy" status is defined by the absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead EKG, and laboratory tests on blood and urine.
Exclusion Criteria:
- Inability to provide informed consent in English or Spanish
Concerns arising at screening visit (any of the following):
i. Unwillingness to fast (except water) for up to 15 hours
ii. Documented weight change of ≥ 3.0% of baseline within the previous 6 months
iii. Abnormal blood pressure
- Systolic blood pressure < 90 mm Hg or > 160 mm Hg, and/or
- Diastolic blood pressure < 60 mm Hg or > 100 mm Hg
iv. Abnormal resting heart rate ≤ 60 bpm or ≥ 100 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
v. Abnormal screening electrocardiogram (or if on file, performed within previous 90 d)
- Non-sinus rhythm
- Significant QTc prolongation (≥ 480 ms)
- New or previously unknown ischaemic changes that persist on repeat EKG:
- ST elevations
- T-wave inversions
vi. Abnormal screening serum electrolytes and/or liver function tests
vii. Laboratory evidence of prediabetic state or diabetes mellitus:
- Hemoglobin A1c ≥ 5.7%, and/or
- Fasting plasma glucose ≥ 100 mg/dL
viii. Abnormal fasting lipids at screening (either of the following)
- Triglycerides ≥ 150 mg/dL
- LDL-cholesterol ≥ 160 mg/dL
ix. Positive qualitative human chorionic gonadotropin beta subunit (β-hCG) (i.e., pregnancy test) in women of childbearing potential
COVID-19 precautions
i. Unwillingness to comply with masking requirements per hospital policy
ii. Active, documented COVID-19 at any time after screening through study completion
Reproductive concerns
i. Women of childbearing potential not using highly effective contraception, defined as:
- Surgical sterilization (e.g., bilateral tubal occlusion, bilateral oophorectomy and/or salpingectomy, hysterectomy)
- Combined oral contraceptive pills taken daily, including during the study
- Intrauterine device (levonorgestrel-eluting or copper) active at the time of the study
- Medroxyprogesterone acetate (Depo-Provera®) injection active at the time of the study
- Etonogestrel implants (e.g., Implanon®, etc.) active at the time of the study
- Norelgestromin/ethinyl estradiol transdermal system (e.g., Ortho-Evra®) active at the time of the study
ii. Women currently pregnant
iii. Women currently breastfeeding
Any clinically relevant history or the presence of any active or chronic disease, including respiratory, renal, hepatic, gastrointestinal, hematological, lymphatic, neurological, cardiovascular, psychiatric, etc. disease or diseases except for:
- Osteoarthritis, not using chronic anti-inflammatory medications
- Non-melanoma skin cancer, localized and not receiving systemic therapy
- N.B. Minor chronic health problems that do not impair overall health/functional status and are judged unlikely to interfere with study conduct or data analysis may be permitted at the discretion of the PI
Currently taking any prescription medications other than vitamins or other nutritional supplements, subject to review by the PI
o Any participant using biotin (vitamin B7) at >1000 international units per day must not take it for 3 d prior to any study blood draw due to interference with laboratory assays
Dermatologic concerns
- History of cutaneous and/or mucosal eruptive reactions to food or drugs, including, but not limited to, rash or urticaria
- Active skin conditions requiring ongoing care by a dermatologist except for localized non-melanoma skin cancer (not receiving systemic therapy)
- Clinical concern for alcohol overuse at screening and/or by participant's report of consuming more than 14 standard drinks per week for males or more than 7 standard drinks per week for females
- Current use of illicit drugs
- Tobacco smoking currently or within the previous 6 months
- History of or ongoing febrile illness within 30 days of screening
- Any other disease or condition or laboratory value that, in the opinion of the investigator, would place the participant at an unacceptable risk and/or interfere with the analysis of study data.
- Known allergy/hypersensitivity to any component of the medicinal product formulations (including soy or cow dairy), other biologics, venipuncture materials, plastics, adhesive or silicone, or ongoing clinically important allergy/hypersensitivity as judged by the investigator.
- Dietary restrictions (e.g.., vegan, kosher, halal) on gelatin present in overencapsulation
- Concurrent enrollment in another clinical study of any investigational drug therapy or use of any biologicals within 6 months prior to screening or within 5 half-lives of an investigational agent or biologic, whichever is longer.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Alpelisib treatment
Participants will ingest a single dose of alpelisib 300 mg (two overencapsulated 150-mg tablets)
|
Participants will ingest two overencapsulated tablets of alpelisib at 23:00, along with a saltine cracker.
Other Names:
Continuous glucose monitoring for 24 hours (double blinded)
Participants will drink Trutol glucose beverage (D-glucose 75 g in 10 fl oz) and blood will be sampled at baseline and at 15, 30, 60, 90, 120, 150, and 180 minutes.
Participants will consume a quantity of BOOST Plus calculated to match their daily caloric needs, divided over three liquid meals.
|
Placebo Comparator: Placebo treatment
Participants will ingest a single dose of placebo (two capsules filled with microcrystalline cellulose)
|
Continuous glucose monitoring for 24 hours (double blinded)
Participants will drink Trutol glucose beverage (D-glucose 75 g in 10 fl oz) and blood will be sampled at baseline and at 15, 30, 60, 90, 120, 150, and 180 minutes.
Participants will consume a quantity of BOOST Plus calculated to match their daily caloric needs, divided over three liquid meals.
Participants will ingest two capsules filled with microcrystalline cellulose at 23:00, along with a saltine cracker.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Fasting plasma glucose
Time Frame: Day 4 (10 hours after dose)
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Fasting plasma glucose (units: mg/dL) after a single dose of alpelisib vs placebo.
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Day 4 (10 hours after dose)
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Fasting serum insulin
Time Frame: Day 4 (10 hours after dose)
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Fasting serum insulin (units: micro-international units per milliliter, µIU/mL) levels after a single dose of alpelisib vs placebo.
|
Day 4 (10 hours after dose)
|
Fasting serum C-peptide
Time Frame: Day 4 (10 hours after dose)
|
Fasting serum C-peptide (units: ng/mL) after a single dose of alpelisib vs placebo.
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Day 4 (10 hours after dose)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overnight glucose profile
Time Frame: Days 3-4 (Approximately 24 hours)
|
Glucose levels (units: mg/dL) serially sampled in interstitial fluid by continuous glucose monitor
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Days 3-4 (Approximately 24 hours)
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Plasma glucose levels during OGTT
Time Frame: Day 4 (Up to 180 minutes from the start of the procedure)
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Measurement of plasma glucose levels (units: mg/dL) during OGTT in alpelisib vs placebo
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Day 4 (Up to 180 minutes from the start of the procedure)
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Plasma glucose area under the curve (AUC) during OGTT
Time Frame: Day 4 (Up to 180 minutes from the start of the procedure)
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Plasma glucose AUC (units: arbitrary units) during OGTT in alpelisib vs placebo
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Day 4 (Up to 180 minutes from the start of the procedure)
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Serum insulin levels during OGTT
Time Frame: Day 4 (Up to 180 minutes from the start of the procedure)
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Measurement of serum insulin levels (units: µIU/mL) during OGTT in alpelisib vs placebo
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Day 4 (Up to 180 minutes from the start of the procedure)
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Serum insulin area under the curve (AUC) during OGTT
Time Frame: Day 4 (Up to 180 minutes from the start of the procedure)
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Serum insulin AUC (units: arbitrary units) during OGTT in alpelisib vs placebo
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Day 4 (Up to 180 minutes from the start of the procedure)
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Serum triglyceride levels during OGTT
Time Frame: Day 4 (Up to 180 minutes from the start of the procedure)
|
Measurement of serum triglyceride levels (units: mg/dL) during OGTT in alpelisib vs placebo
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Day 4 (Up to 180 minutes from the start of the procedure)
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Serum free fatty acid levels during OGTT
Time Frame: Day 4 (Up to 180 minutes from the start of the procedure)
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Measurement of serum free fatty acid levels (units: mmol/L) during OGTT in alpelisib vs placebo
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Day 4 (Up to 180 minutes from the start of the procedure)
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Fasting serum total cholesterol levels
Time Frame: Day 4 (10 hours after dose)
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Measurement of fasting serum total cholesterol (units: mg/dL) in alpelisib vs placebo
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Day 4 (10 hours after dose)
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Fasting serum high-density lipoprotein (HDL) cholesterol levels
Time Frame: Day 4 (10 hours after dose)
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Measurement of fasting serum HDL cholesterol (units: mg/dL) in alpelisib vs placebo
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Day 4 (10 hours after dose)
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Fasting serum low-density lipoprotein (LDL) cholesterol levels
Time Frame: Day 4 (10 hours after dose)
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Measurement of fasting serum LDL cholesterol (units: mg/dL) in alpelisib vs placebo
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Day 4 (10 hours after dose)
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Fasting serum or plasma apolipoprotein B levels
Time Frame: Day 4 (10 hours after dose)
|
Measurement of serum or plasma apolipoprotein B (units: mg/dL) in alpelisib vs placebo
|
Day 4 (10 hours after dose)
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Joshua R Cook, MD, PhD, Columbia University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- AAAU3423
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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