A Phase 1 interventional study of Alpelisib 150 mg [Piqray], 2 overencapsulated tablets (total: 300 mg) and Placebo (microcrystalline cellulose), 2 capsules in Insulin Resistance, Hyperinsulinemia and Dyslipidemias, sponsored by Columbia University. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-12-21.
Sponsored by Columbia University · Phase 1, Interventional, and Basic science
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:
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).
Non-alcoholic fatty liver disease (NAFLD) is an under-appreciated complication of lipid dysmetabolism in type 2 diabetes (T2DM). Although it appears that insulin resistance (IR) is a mechanism common to both, the mechanisms linking IR to unhealthy fat accumulation in liver remains unclear. "Pure" IR would be expected to disinhibit hepatic glucose production while dampening hepatic triglyceride (TG) biosynthesis, but the excessive hepatic de novo lipogenesis (DNL) of IR-associated NAFLD (IR-NAFLD) suggests that hepatic IR is "selective." However, the concept of IR selectivity is controversial, and because of clinical heterogeneity, lead-time discrepancies, co-morbidities, and medication effects, parsing out this pathophysiologic conundrum in humans is challenging. The investigators ultimately plan to test whether the multifactorial IR in patients with NAFLD is selective by determining if inducing a discrete, "pure" form of IR, via pharmacologic inhibition of phosphoinositide-3-kinase (PI3K) with alpelisib, attenuates excessive DNL. However, because of the potential toxicities of alpelisib, the investigators first must test whether they can induce IR with a single dose. In order to ensure participants' safety, the investigators propose herein to perform a randomized, placebo-controlled, pilot \& feasibility study of a single dose of alpelisib in healthy volunteers. Following a baseline blood draw on Day 1, participants will be fitted with a continuous glucose monitor. Once lab test results are confirmed as non-exclusionary, randomized participants will be instructed on Day 3 to consume their calculated total daily caloric needs in the form of a nutritional beverage, divided evenly over three meals, and otherwise will fast. On the evening of Day 3, participants will ingest a single dose either of placebo or alpelisib. The following morning (Day 4), about 10 hours later, blood will be drawn to check fasting levels of glucose, insulin, and certain lipid/lipoprotein parameters; the continuous glucose monitor will be removed at that point. Participants will then undergo an oral glucose tolerance test (OGTT) during which investigators will measure glucose, insulin, and lipid (triglycerides, free fatty acids) levels. If the investigators are able to determine reliable induction after a single dose of alpelisib, they will be able to move on to test its effect on volunteers with IR-NAFLD.
2,969 studies on the registry are indexed under Insulin Resistance; 338 are open to participants now.
This study's enrollment of 23 is below the median of 40 across 2,369 interventional studies indexed under Insulin Resistance.
Browse Insulin Resistance studies →Columbia University is the lead sponsor of 1,136 studies on the registry; 195 are open to participants now.
Of its 180 completed or terminated interventional studies of FDA-regulated products, 148 (82%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
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
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 (or if on file, performed within previous 90 d)
vi. Abnormal screening serum electrolytes and/or liver function tests
vii. Laboratory evidence of prediabetic state or diabetes mellitus:
viii. Abnormal fasting lipids at screening (either of the following)
ix. Positive qualitative human chorionic gonadotropin beta subunit (β-hCG) (i.e., pregnancy test) in women of
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 , defined as:
ii. Women currently pregnant
iii. Women currently breastfeeding
Any 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:
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
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will ingest a single dose of alpelisib 300 mg (two overencapsulated 150-mg tablets)
Drug: Alpelisib 150 mg [Piqray], 2 overencapsulated tablets (total: 300 mg) · Device: FreeStyle Libre Pro · Diagnostic Test: Oral glucose tolerance test (OGTT) with Trutol glucose beverage · Dietary Supplement: BOOST Plus nutritional beverage
Participants will ingest a single dose of placebo (two capsules filled with microcrystalline cellulose)
Drug: Placebo (microcrystalline cellulose), 2 capsules · Device: FreeStyle Libre Pro · Diagnostic Test: Oral glucose tolerance test (OGTT) with Trutol glucose beverage · Dietary Supplement: BOOST Plus nutritional beverage
Participants will ingest two overencapsulated tablets of alpelisib at 23:00, along with a saltine cracker.
Also known as: Piqray
Participants will ingest two capsules filled with microcrystalline cellulose at 23:00, along with a saltine cracker.
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.
Fasting plasma glucose
Fasting plasma glucose (units: mg/dL) after a single dose of alpelisib vs placebo.
Time frame: Day 4 (10 hours after dose)
Fasting serum insulin
Fasting serum insulin (units: micro-international units per milliliter, µIU/mL) levels after a single dose of alpelisib vs placebo.
Time frame: Day 4 (10 hours after dose)
Fasting serum C-peptide
Fasting serum C-peptide (units: ng/mL) after a single dose of alpelisib vs placebo.
Time frame: Day 4 (10 hours after dose)
Overnight glucose profile
Glucose levels (units: mg/dL) serially sampled in interstitial fluid by continuous glucose monitor
Time frame: Days 3-4 (Approximately 24 hours)
Plasma glucose levels during OGTT
Measurement of plasma glucose levels (units: mg/dL) during OGTT in alpelisib vs placebo
Time frame: Day 4 (Up to 180 minutes from the start of the procedure)
Plasma glucose area under the curve (AUC) during OGTT
Plasma glucose AUC (units: arbitrary units) during OGTT in alpelisib vs placebo
Time frame: Day 4 (Up to 180 minutes from the start of the procedure)
Serum insulin levels during OGTT
Measurement of serum insulin levels (units: µIU/mL) during OGTT in alpelisib vs placebo
Time frame: Day 4 (Up to 180 minutes from the start of the procedure)
Serum insulin area under the curve (AUC) during OGTT
Serum insulin AUC (units: arbitrary units) during OGTT in alpelisib vs placebo
Time frame: Day 4 (Up to 180 minutes from the start of the procedure)
Serum triglyceride levels during OGTT
Measurement of serum triglyceride levels (units: mg/dL) during OGTT in alpelisib vs placebo
Time frame: Day 4 (Up to 180 minutes from the start of the procedure)
Serum free fatty acid levels during OGTT
Measurement of serum free fatty acid levels (units: mmol/L) during OGTT in alpelisib vs placebo
Time frame: Day 4 (Up to 180 minutes from the start of the procedure)
Fasting serum or plasma apolipoprotein B levels
Measurement of serum or plasma apolipoprotein B (units: mg/dL) in alpelisib vs placebo
Time frame: Day 4 (10 hours after dose)
Fasting serum total cholesterol levels
Measurement of fasting serum total cholesterol (units: mg/dL) in alpelisib vs placebo
Time frame: Day 4 (10 hours after dose)
Fasting serum high-density lipoprotein (HDL) cholesterol levels
Measurement of fasting serum HDL cholesterol (units: mg/dL) in alpelisib vs placebo
Time frame: Day 4 (10 hours after dose)
Fasting serum low-density lipoprotein (LDL) cholesterol levels
Measurement of fasting serum LDL cholesterol (units: mg/dL) in alpelisib vs placebo
Time frame: Day 4 (10 hours after dose)
Plan to share: Yes — Blood samples will be banked in our Insulin Resistance Biobank and will be made available to other researchers for legitimate research purposes upon request. Associated data will be shared along with specimens in the smallest possible quantity and on a need-to-know basis. No Protected Health Information (PHI) will ever be disclosed to other researchers. All requests will be reviewed by the PI for scientific merit and samples/data will be transferred only upon completion of an Institutional Review Board-approved Material Transfer Agreement (MTA) and/or Data Use Agreement (DUA), as appropriate.
Supporting information: Study protocol
Time frame: Indefinitely following study completion.
No publications or documents are linked to this record.
Ran from May 2023 to primary completion in Dec 2023, 6 months.
Of 51 non-industry phase 1 interventional studies under Insulin Resistance, half reached primary completion within 26 months of starting (the median), counting those still running; a quarter within 14 and three quarters within 80. This study's 6 months is below that.
Counting every sponsor, half of 65 studies reached it within 24 months; a quarter within 13 and three quarters within 67.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Dec 2023. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Alpelisib