[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100543301":3},{"organization":4,"armGroups":7,"interventions":30,"overallOfficials":64,"centralContacts":68,"locations":78,"responsibleParty":105,"collaborators":108,"id":116,"slug":72,"hasResults":117,"nctId":118,"briefTitle":119,"officialTitle":119,"acronym":72,"eligibilityCriteria":120,"healthyVolunteers":121,"sex":122,"minAge":123,"maxAge":124,"enrollmentInfo":125,"targetDuration":72,"studyType":128,"phases":129,"briefSummary":131,"conditions":132,"keywords":137,"overallStatus":81,"whyStopped":72,"lastUpdateSubmitDate":143,"lastUpdatePostDateStruct":144,"startDateStruct":147,"completionDateStruct":149,"leadSponsor":151,"locationsCount":152},{"fullName":5,"class":6},"Columbia University","OTHER",[8,18,22,26],{"label":9,"type":10,"description":11,"interventionNames":12},"Placebo then alpelisib (Insulin Sensitive group)","EXPERIMENTAL","On Study Visit 1, participants in the Insulin Sensitive (IS) group will undergo fasting and refed measurement of de novo lipogenesis (DNL) and endogenous glucose production (EGP) following a single dose of placebo. Then, 2-8 weeks later on Study Visit 2, participants will undergo measurement of DNL and EGP after a single dose of alpelisib 300 mg.",[13,14,15,16,17],"Drug: Alpelisib 300 mg","Drug: Placebo","Drug: [1-13C] sodium acetate","Drug: [6,6-2H2] D-glucose","Dietary Supplement: Nestlé BOOST Plus",{"label":19,"type":10,"description":20,"interventionNames":21},"Alpelisib then placebo (Insulin Sensitive group)","On Study Visit 1, participants in the Insulin Sensitive (IS) group will undergo fasting and refed measurement of de novo lipogenesis (DNL) and endogenous glucose production (EGP) following a single dose of alpelisib 300 mg. Then, 2-8 weeks later on Study Visit 2, participants will undergo measurement of DNL and EGP after a single dose of placebo.",[13,14,15,16,17],{"label":23,"type":10,"description":24,"interventionNames":25},"Placebo then alpelisib (Insulin Resistant group)","On Study Visit 1, participants in the Insulin Resistant (IR) group will undergo fasting and refed measurement of de novo lipogenesis (DNL) and endogenous glucose production (EGP) following a single dose of placebo. Then, 2-8 weeks later on Study Visit 2, participants will undergo measurement of DNL and EGP after a single dose of alpelisib 300 mg.",[13,14,15,16,17],{"label":27,"type":10,"description":28,"interventionNames":29},"Alpelisib then placebo (Insulin Resistant group)","On Study Visit 1, participants in the Insulin Resistant (IR) group will undergo fasting and refed measurement of de novo lipogenesis (DNL) and endogenous glucose production (EGP) following a single dose of alpelisib 300 mg. Then, 2-8 weeks later on Study Visit 2, participants will undergo measurement of DNL and EGP after a single dose of placebo.",[13,14,15,16,17],[31,38,44,50,57],{"type":32,"name":33,"description":34,"armGroupLabels":35,"otherNames":36},"DRUG","Alpelisib 300 mg","All participants will ingest one dose of alpelisib 300 mg (2 x 150-mg overencapsulated tablets) on one of two study admissions.",[27,19,23,9],[37],"Piqray",{"type":32,"name":39,"description":40,"armGroupLabels":41,"otherNames":42},"Placebo","All participants will ingest one dose of placebo (2 overencapuslated doses of microcrystalline cellulose) on one of two study admissions.",[27,19,23,9],[43],"Placebo capsules",{"type":32,"name":45,"description":46,"armGroupLabels":47,"otherNames":48},"[1-13C] sodium acetate","All participants will receive continuous infusions of \\[1-13C\\] sodium acetate for up to 23 hours on both study visits in order to quantify de novo lipogenesis (DNL). (non-experimental)",[27,19,23,9],[49],"C13A",{"type":32,"name":51,"description":52,"armGroupLabels":53,"otherNames":54},"[6,6-2H2] D-glucose","All participants will receive continuous infusions of \\[6,6-2H2\\] D-glucose for up to 15 hours on both study visits in order to quantify de novo lipogenesis (DNL). (non-experimental)",[27,19,23,9],[55,56],"D2-glucose","D2G",{"type":58,"name":59,"description":60,"armGroupLabels":61,"otherNames":62},"DIETARY_SUPPLEMENT","Nestlé BOOST Plus","All participants will ingest standardized mixed meals of Nestlé BOOST Plus on Study Day 1 and then smaller portions hourly x 8 hours on Study Day 2 of each study visit. (non-experimental)",[27,19,23,9],[63],"Boost drink",[65],{"name":66,"affiliation":5,"role":67},"Joshua R Cook, MD, PhD","PRINCIPAL_INVESTIGATOR",[69,74],{"name":66,"role":70,"phone":71,"phoneExt":72,"email":73},"CONTACT","2123056289",null,"jrc2175@cumc.columbia.edu",{"name":75,"role":70,"phone":76,"phoneExt":72,"email":77},"Ishwari Nagnur","2123059336","imn2113@cumc.columbia.edu",[79],{"facility":80,"status":81,"city":82,"state":82,"zip":83,"country":84,"countryCode":85,"cosmosGeoPoint":86,"geoPoint":91,"contacts":92},"Columbia University Irving Medical Center","RECRUITING","New York","10032","United States","US",{"type":87,"coordinates":88},"Point",[89,90],-74.00597,40.71427,{"lat":90,"lon":89},[93,95,97,98,101,103],{"name":66,"role":70,"phone":94,"phoneExt":72,"email":73},"212-305-6289",{"name":75,"role":70,"phone":76,"phoneExt":72,"email":96},"zds2120@cumc.columbia.edu",{"name":66,"role":67,"phone":72,"phoneExt":72,"email":72},{"name":99,"role":100,"phone":72,"phoneExt":72,"email":72},"Blandine Laferrère, MD, PhD","SUB_INVESTIGATOR",{"name":102,"role":100,"phone":72,"phoneExt":72,"email":72},"Henry N Ginsberg, MD",{"name":104,"role":100,"phone":72,"phoneExt":72,"email":72},"Julia J Wattacheril, MD",{"type":67,"investigatorFullName":106,"investigatorTitle":107,"investigatorAffiliation":5,"oldNameTitle":72,"oldOrganization":72},"Joshua Cook","Assistant Professor of Medicine",[109,111,114],{"name":110,"class":6},"University of California, Berkeley",{"name":112,"class":113},"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","NIH",{"name":115,"class":6},"Stanford University","100543301",false,"NCT06354088","Human Models of Selective Insulin Resistance: Alpelisib, Part I","Inclusion Criteria:\n\n1. Adults aged 18-70 years\n2. Able to understand written and spoken English and\u002For Spanish\n3. Body mass index of:\n\n   * For Group IS: BMI 18-25 kg\u002Fm2\n   * For Group IR: BMI 30-45 kg\u002Fm2\n4. Evidence of insulin sensitivity or insulin resistance:\n\n   * Insulin sensitive (for Group IS) defined as all of the following: (1) Fasting serum insulin ≤ 10 µIU\u002FmL, (2) Absence of dysglycemia (fasting plasma glucose \\\u003C 100 mg\u002FdL and hemoglobin A1c \\\u003C 5.7%), (3) Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) score \\\u003C 2.5, and (4) Fibrosis-4 (FIB-4) score \\\u003C 1.3\n   * Insulin resistant (for Group IR) defined as fasting serum insulin ≥ 13 µIU\u002FmL plus at least one of the following: (1) Presence of prediabetic state (fasting plasma glucose 100-125 mg\u002FdL and\u002For hemoglobin A1c 5.7-6.4%), and\u002For HOMA-IR ≥ 2.5\n\nExclusion Criteria:\n\n1. Inability to provide informed consent in English or Spanish\n2. Concerns arising at screening visit:\n\n   * Abnormal vital signs: (1) Systolic blood pressure \\\u003C 90 mm Hg or \\> 160 mm Hg and\u002For (2) Diastolic blood pressure \\\u003C 55 mm Hg or \\> 100 mm Hg and\u002For (3) Abnormal resting heart rate \\\u003C 55 bpm (except at PI's discretion) or ≥ 110 bpm\n   * Abnormal screening serum electrolytes judged by the PI to be potentially clinically significant, including liver function abnormalities (either of the following): (1) Transaminases (AST or ALT) \\> 3.0 x the upper limit of normal and\u002For (2) Total bilirubin \\> 1.25 x the upper limit of normal\n   * Laboratory evidence of diabetes mellitus: (1) Hemoglobin A1c ≥ 6.5%, and\u002For (2) Fasting plasma glucose ≥ 126 mg\u002FdL\n3. Reproductive concerns i. Positive qualitative β-hCG (i.e., pregnancy test) in women of childbearing potential ii. Women currently pregnant iii. Women currently breastfeeding\n4. Concerns related to glucose metabolism\n\n   * History of having met any of the American Diabetes Association's definitions of diabetes mellitus (i.e., overt diabetes)\n   * History of gestational diabetes mellitus within the previous 5 years\n   * Use of most antidiabetic medications (other than metformin) within the 90 days prior to screening: thiazolidinediones, sulfonylureas, meglitinides, dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, amylin mimetics, acarbose, insulin iv. Clinical concern for absolute insulin deficiency (e.g., type 1 diabetes, pancreatic disease)\n5. Concerns related to lipid metabolism\n\n   * Known diagnoses of familial hypercholesterolemia, familial combined hyperlipidemia, or familial hyperchylomicronemia in the participant or a first-degree relative\n   * Use of certain lipid-lowering drugs within 14 d prior to screening visit: fibrates (e.g., fenofibrate, gemfibrozil), prescription-strength omega-3 fatty acids (e.g., icosapent ethyl), high-dose niacin (\\>100 mg daily)\n6. Known, documented history, at the time of screening, of any of the following medical conditions:\n\n   * Significant cardiovascular diseases (N.B. uncomplicated hypertension is not exclusionary)\n   * Severe liver disease, including advanced fibrosis (e.g., fibrosis score F3-F4 by vibration-controlled transient elastography) and cirrhosis\n   * Psychiatric diseases causing functional impairment that: (1) Are or have been decompensated within 1 year of screening, and\u002For (2) Require use of anti-dopaminergic antipsychotic drugs associated with significant weight gain\u002Fmetabolic dysfunction (e.g., clozapine, olanzapine)\n   * Venous thromboembolic disease (deep vein thrombosis or pulmonary embolism) or any required use of therapeutic anticoagulation\n   * Bleeding disorders, including due to anticoagulation, or significant anemia (see above)\n   * Active malignancy, or hormonally active benign neoplasm, except allowances for non-melanoma skin cancer and differentiated thyroid cancer (Stage I only)\n7. Clinical concern for increased risk of volume overload, including due to medications and\u002For heart\u002Fliver\u002Fkidney problems, as listed above\n8. Use of oral or parenteral corticosteroids (at greater than prednisone 5 mg daily, or equivalent) for more than 3 days within the previous 30 days; topical and inhaled formulations are permitted\n9. History of certain weight-loss (bariatric) surgery, including:\n\n   * Roux-en-Y gastric bypass\n   * Biliopancreatic diversion\n   * Restrictive procedures (lap band, sleeve gastrectomy) performed within the past 6 months\n10. Clinical concern for alcohol overuse based on chart review and\u002For by recruit's report of more than 14 standard drinks per week for males or more than 7 standard drinks per week for females\n11. Regular use of tobacco, either daily or an average of at least 1 cigarette per day, and\u002For nicotine vaping more than 1 day per week\n12. Clinical concern for use of illicit drugs other than marijuana or lawfully prescribed medications based on recruit's report, chart review, and point-of-care urine drug test at screening\n13. History of or ongoing febrile illness within 30 days of screening\n14. Any other disease or condition or laboratory value that, in the opinion of the investigator, would place the participant at an unacceptable risk and\u002For interfere with the analysis of study data.\n15. Known allergy\u002Fhypersensitivity to any component of the medicinal product formulations (including soy, cow dairy, or gluten), other biologics, venipuncture materials, plastics, adhesive or silicone, or ongoing clinically important allergy\u002Fhypersensitivity as judged by the investigator.\n16. Dietary restrictions (e.g., vegan, kosher, halal) on gelatin present in overencapsulation\n17. Concurrent enrollment in another clinical study of any investigational drug\u002Fbiologic therapy within 6 months prior to screening or within 5 half-lives of an investigational agent or biologic, whichever is longer.\n\n    * Prior participation in other studies led by Dr. Cook (PI) is excluded from this prohibition according to his medical\u002Fscientific judgment.",true,"ALL","18 Years","70 Years",{"count":126,"type":127},32,"ESTIMATED","INTERVENTIONAL",[130],"PHASE1","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.\n\nThe objective is to evaluate the effect of lowering insulin levels, while maintaining constant mild hyperglycemia, on plasma glucose and lipid levels.",[133,134,135,136],"Insulin Resistance","Prediabetic State","Overweight and Obesity","Non-Alcoholic Fatty Liver Disease",[138,139,136,140,141,142],"Insulin resistance","Hyperinsulinemia","Hepatic steatosis","De novo lipogenesis","Glucose production","2026-04-06",{"date":145,"type":146},"2026-04-09","ACTUAL",{"date":148,"type":146},"2024-04-24",{"date":150,"type":127},"2026-12-31",{"name":5,"class":6},1]