protocolSection identificationModule nctId: NCT06354088, orgStudyIdInfo id: AAAU9636, briefTitle: Human Models of Selective Insulin Resistance: Alpelisib, Part I, statusModule overallStatus: RECRUITING, startDateStruct date: 2024-04-24, primaryCompletionDateStruct date: 2026-05, completionDateStruct date: 2026-12, studyFirstPostDateStruct date: 2024-04-09, lastUpdatePostDateStruct date: 2024-04-29, sponsorCollaboratorsModule leadSponsor name: Columbia University, class: OTHER, collaborators name: University of California, Berkeley, descriptionModule briefSummary: 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., conditionsModule conditions: Insulin Resistance, conditions: Prediabetic State, conditions: Overweight and Obesity, conditions: Non-Alcoholic Fatty Liver Disease, designModule studyType: INTERVENTIONAL, phases: PHASE1, designInfo allocation: RANDOMIZED, interventionModel: CROSSOVER, primaryPurpose: BASIC_SCIENCE, maskingInfo masking: DOUBLE, whoMasked: PARTICIPANT, whoMasked: INVESTIGATOR, enrollmentInfo count: 32, type: ESTIMATED, armsInterventionsModule interventions name: Alpelisib 300 mg, interventions name: Placebo, interventions name: [1-13C] sodium acetate, interventions name: [6,6-2H2] D-glucose, interventions name: Nestlé BOOST Plus, outcomesModule primaryOutcomes measure: Hepatic de novo lipogenesis (DNL) (absolute value), primaryOutcomes measure: Hepatic de novo lipogenesis (DNL) (relative value), primaryOutcomes measure: Endogenous glucose production (EGP) (absolute value), primaryOutcomes measure: Endogenous glucose production (EGP) (relative value), primaryOutcomes measure: Serum insulin level, primaryOutcomes measure: Plasma glucose level, secondaryOutcomes measure: Triglycerides level, secondaryOutcomes measure: Free fatty acids level, secondaryOutcomes measure: Glucose kinetics: rate of appearance (absolute value), secondaryOutcomes measure: Glucose kinetics: rate of appearance (relative value), secondaryOutcomes measure: Glucose kinetics: rate of disappearance (absolute value), secondaryOutcomes measure: Glucose kinetics: rate of disappearance (relative value), otherOutcomes measure: Apolipoprotein B level, eligibilityModule sex: ALL, minimumAge: 18 Years, maximumAge: 70 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: Columbia University Irving Medical Center, status: RECRUITING, city: New York, state: New York, zip: 10032, country: United States, contacts name: Joshua R Cook, MD, PhD, role: CONTACT, phone: 212-305-6289, email: jrc2175@cumc.columbia.edu, contacts name: Zachary D Sone, role: CONTACT, phone: 2123059336, email: zds2120@cumc.columbia.edu, contacts name: Joshua R Cook, MD, PhD, role: PRINCIPAL_INVESTIGATOR, contacts name: Blandine Laferrère, MD, PhD, role: SUB_INVESTIGATOR, contacts name: Henry N Ginsberg, MD, role: SUB_INVESTIGATOR, contacts name: Julia J Wattacheril, MD, role: SUB_INVESTIGATOR, geoPoint lat: 40.71427, lon: -74.00597, hasResults: False