[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100558999":3},{"organization":4,"armGroups":7,"interventions":28,"overallOfficials":88,"centralContacts":92,"locations":101,"responsibleParty":128,"collaborators":131,"id":137,"slug":138,"hasResults":139,"nctId":140,"briefTitle":141,"officialTitle":141,"acronym":40,"eligibilityCriteria":142,"healthyVolunteers":139,"sex":143,"minAge":144,"maxAge":145,"enrollmentInfo":146,"targetDuration":40,"studyType":149,"phases":150,"briefSummary":152,"conditions":153,"keywords":160,"overallStatus":165,"whyStopped":40,"lastUpdateSubmitDate":166,"lastUpdatePostDateStruct":167,"startDateStruct":170,"completionDateStruct":172,"leadSponsor":174,"locationsCount":175},{"fullName":5,"class":6},"Columbia University","OTHER",[8,24],{"label":9,"type":10,"description":11,"interventionNames":12},"Maintenance hyperinsulinemia (MH) Protocol then Reduction toward Euinsulinemia (RE) Protocol","EXPERIMENTAL","On Pancreatic Clamp Visit 1 (MH Protocol), the insulin infusion rate (IIR) will be set to approximately replicate participants' endogenous fasting serum insulin levels based on screening visit data for the duration of the pancreatic clamp. On Pancreatic Clamp Visit 2 (RE Protocol), the IIR will be set to reduce serum insulin levels to roughly 50% of the screening fasting serum insulin for the duration of the pancreatic clamp. In both cases, plasma glucose will be clamped to approximately 140 mg\u002FdL +\u002F- 10%.",[13,14,15,16,17,18,19,20,21,22,23],"Drug: Insulin human","Drug: Octreotide Acetate","Drug: Glucagon","Drug: Growth Hormone, Human","Drug: 20% D-glucose (aq)","Diagnostic Test: [6,6-2H2] D-glucose","Diagnostic Test: [1-13C1] sodium acetate","Dietary Supplement: Nestle BOOST Plus","Dietary Supplement: KIND Bar","Device: Harvard Apparatus PHD ULTRA CP syringe pump","Device: Yellow Springs Instruments (YSI) 2500 Biochemistry Glucose\u002FLactate Analyzer",{"label":25,"type":10,"description":26,"interventionNames":27},"Reduction toward euinsulinemia (RE) protocol","On Pancreatic Clamp Visit 1 (RE Protocol), the insulin infusion rate (IIR) will be set to produce serum insulin levels of approximately 50% that of the screening fasting serum insulin level for the full duration of the pancreatic clamp. On Pancreatic Clamp Visit 2 (MH Protocol), the IIR will be set to approximately replicate the full fasting serum insulin for the duration of the pancreatic clamp. In both cases, plasma glucose will be clamped to approximately 140 mg\u002FdL +\u002F- 10%.",[13,14,15,16,17,18,19,20,21,22,23],[29,36,41,45,51,57,64,70,75,79,84],{"type":30,"name":31,"description":32,"armGroupLabels":33,"otherNames":34},"DRUG","Insulin human","Insulin infusion rate (IIR) will be determined either to maintain fasting serum insulin levels (MH protocol) or to reduce fasting serum insulin levels by approximately 50% toward euinsulinemia (RE protocol).",[9,25],[35],"Novolin-R, Humulin-R",{"type":30,"name":37,"description":38,"armGroupLabels":39,"otherNames":40},"Octreotide Acetate","Octreotide will be infused at 30 ng\u002Fkg\u002Fmin to suppress endogenous insulin, glucagon, and growth hormone secretion. Co-administered with glucagon and rhGH.",[9,25],null,{"type":30,"name":42,"description":43,"armGroupLabels":44,"otherNames":40},"Glucagon","Glucagon will be replaced at a constant rate of up to 0.65 ng\u002Fkg\u002Fmin to maintain baseline counterregulatory response. Co-administered with octreotide and rhGH.",[9,25],{"type":30,"name":46,"description":47,"armGroupLabels":48,"otherNames":49},"Growth Hormone, Human","Recombinant human growth hormone (rhGH) will be replaced at a constant rate of up to 3 ng\u002Fkg\u002Fmin to maintain baseline counterregulatory response. Co-administered with octreotide and glucagon.",[9,25],[50],"Omnitrope, Zomacton",{"type":30,"name":52,"description":53,"armGroupLabels":54,"otherNames":55},"20% D-glucose (aq)","20% D-glucose (aq) (D20W) will be administered to counteract hypoglycemia or strongly downward blood glucose trends, as needed.",[9,25],[56],"D20W",{"type":58,"name":59,"description":60,"armGroupLabels":61,"otherNames":62},"DIAGNOSTIC_TEST","[6,6-2H2] D-glucose","Stable isotope tracer administered to calculate glucose kinetics during pancreatic clamp.",[9,25],[63],"D2-glucose, D2G",{"type":58,"name":65,"description":66,"armGroupLabels":67,"otherNames":68},"[1-13C1] sodium acetate","Stable isotope tracer administered to calculate de novo lipogenesis during pancreatic clamp.",[9,25],[69],"13C-acetate, C13A",{"type":71,"name":72,"description":73,"armGroupLabels":74,"otherNames":40},"DIETARY_SUPPLEMENT","Nestle BOOST Plus","Nutritional supplement will be administered to provide standardized \"mixed meals\" prior to the pancreatic clamp.",[9,25],{"type":71,"name":76,"description":77,"armGroupLabels":78,"otherNames":40},"KIND Bar","Energy bar snack will be administered the evening before the pancreatic clamp.",[9,25],{"type":80,"name":81,"description":82,"armGroupLabels":83,"otherNames":40},"DEVICE","Harvard Apparatus PHD ULTRA CP syringe pump","Syringe pump used for highly precise administration of insulin, octreotide\u002Fglucagon\u002FrhGH, and D20W (as needed) even at low infusion rates.",[9,25],{"type":80,"name":85,"description":86,"armGroupLabels":87,"otherNames":40},"Yellow Springs Instruments (YSI) 2500 Biochemistry Glucose\u002FLactate Analyzer","Glucose oxidase analyzer used to detect plasma glucose levels at the point of care. YSI have been the gold standard in clamp studies for many years. Two machines will run in parallel to ensure accuracy of results.",[9,25],[89],{"name":90,"affiliation":5,"role":91},"Joshua R Cook, MD, PhD","PRINCIPAL_INVESTIGATOR",[93,97],{"name":90,"role":94,"phone":95,"phoneExt":40,"email":96},"CONTACT","2123056289","jrc2175@cumc.columbia.edu",{"name":98,"role":94,"phone":99,"phoneExt":40,"email":100},"Ishwari Nagnur","2123059336","imn2113@cumc.columbia.edu",[102],{"facility":103,"status":40,"city":104,"state":104,"zip":105,"country":106,"countryCode":107,"cosmosGeoPoint":108,"geoPoint":113,"contacts":114},"Columbia University Irving Medical Center","New York","10032","United States","US",{"type":109,"coordinates":110},"Point",[111,112],-74.00597,40.71427,{"lat":112,"lon":111},[115,118,119,122,124,126],{"name":116,"role":94,"phone":117,"phoneExt":40,"email":96},"Joshua R. Cook, MD, PhD","212-305-6289",{"name":116,"role":91,"phone":40,"phoneExt":40,"email":40},{"name":120,"role":121,"phone":40,"phoneExt":40,"email":40},"Julia J. Wattacheril, MD","SUB_INVESTIGATOR",{"name":123,"role":121,"phone":40,"phoneExt":40,"email":40},"Lindsey A Bordone, MD",{"name":125,"role":121,"phone":40,"phoneExt":40,"email":40},"Henry N Ginsberg, MD",{"name":127,"role":121,"phone":40,"phoneExt":40,"email":40},"Blandine Laferrere, MD, PhD",{"type":91,"investigatorFullName":129,"investigatorTitle":130,"investigatorAffiliation":5,"oldNameTitle":40,"oldOrganization":40},"Joshua Cook","Assistant Professor of Medicine",[132,134],{"name":133,"class":6},"University of California, Berkeley",{"name":135,"class":136},"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","NIH","100558999","phase-1-human-models-of-selective-insulin-resistance-pancreatic-clamp-100558999",false,"NCT06558422","Human Models of Selective Insulin Resistance: Pancreatic Clamp","Inclusion Criteria:\n\n* Men and women, ages 18-65 years\n* Body mass index of 27-50 kg\u002Fm2\n* Able to understand written and spoken English and\u002For Spanish\n* Evidence of insulin resistance, represented by any or all of the following criteria:\n\n  * Meeting either of the American Diabetes Association's definitions for prediabetes or Impaired fasting glucose (IFG) within the previous year and on screening labs:\n\n    1. Prediabetes: Hemoglobin A1c 5.7-6.4%\n    2. IFG: plasma glucose of 100-125 mg\u002FdL after 8-h fast\n* Homeostasis Model of Insulin Resistance (HOMA-IR) score ≥ 2.73\n* Fasting hyperinsulinemia (fasting insulin level ≥ 13 µU\u002FmL) on screening labs\n* Presence of uncomplicated MASLD, defined by vibration-controlled transient elastography (VCTE) as a steatosis score S1-S3 + fibrosis score F0-F2\n* Written informed consent (in English or Spanish) and any locally required authorization (e.g., Health Insurance Portability and Accountability Act) obtained from the participant prior to performing any protocol-related procedures, including screening evaluations.\n\nExclusion Criteria:\n\n* Unable to provide informed consent in English or Spanish\n* Unwillingness to use only bedpan or urinal to void or to refrain from non-emergent mobile device use during the clamp\n* Documented weight loss of ≥ 5% of baseline within the previous 3 months\n* Abnormal blood pressure (including on treatment, if prescribed)\n\n  * Systolic blood pressure \\\u003C 90 mm Hg or \\> 160 mm Hg, and\u002For\n  * Diastolic blood pressure \\\u003C 60 mm Hg or \\> 100 mm Hg\n* Abnormal resting heart rate: \\\u003C 60 or ≥ 110 bpm\n\n  * Sinus brady- or tachycardia that has been worked up and considered benign by the recruit's personal physician may be permitted at the PI's discretion\n* Abnormal screening electrocardiogram (or if on file, performed within previous 90 days)\n* Laboratory evidence of diabetes mellitus:\n\n  * Hemoglobin A1c ≥ 6.5%, and\u002For\n  * Fasting plasma glucose ≥ 126 mg\u002FdL\n* Positive qualitative β-hCG (Human chorionic gonadotropin, β subunit) (i.e., pregnancy test) in women of childbearing potential\n* Positive urine drug screen, except for lawfully prescribed medications and\u002For marijuana\n* Liver function abnormalities (either of the following)\n\n  * Transaminases (AST or ALT) \\> 3.0 x the upper limit of normal\n  * Total bilirubin \\> 1.25 x the upper limit of normal\n* Fasting serum triglycerides at screening ≥ 400 mg\u002FdL\n* Abnormal screening serum electrolytes that are considered potentially significant according to the clinical judgment of the PI\n* Abnormal complete blood count (CBC) (any of the following)\n\n  * Hemoglobin \\\u003C 10 g\u002FdL or hematocrit \\\u003C 30%\n  * Platelet count \\\u003C 100,000\u002FµL\n* Women currently pregnant, measured by serum and\u002For urine β-hCG, or trying to become pregnant\n* Women currently breastfeeding\n* History of having met any of the American Diabetes Association's definitions of diabetes mellitus (i.e., overt diabetes):\n\n  * Hemoglobin A1c ≥ 6.5%, or rapid rise in documented HbA1c values causing clinical concern for evolving insulin deficiency\n  * Plasma glucose ≥ 126 mg\u002FdL after 8-h fast\n  * Plasma glucose of ≥ 200 mg\u002FdL at 2 h after ingestion of a 75-g glucose load\n  * Random plasma glucose ≥ 200 mg\u002FdL associated with typical hyperglycemic symptoms, diabetic ketoacidosis, or hyperglycemic-hyperosmolar state\n* History of gestational diabetes mellitus within the previous 5 years\n* Use of most antidiabetic medications within the 30 days prior to screening\n\n  * Excluded: thiazolidinediones, sulfonylureas, meglitinides, DPP4 inhibitors, GLP-1 receptor agonists, SGLT2 inhibitors, amylin mimetics, acarbose, insulin\n  * Metformin is acceptable provided that recruits meet all of the inclusion criteria at screening\n* Clinical concern for absolute insulin deficiency (e.g., type 1 diabetes, pancreatic disease)\n* Known diagnoses of familial combined hyperlipidemia or familial chylomicronemia syndrome\n* Use of certain lipid-lowering drugs within 30 d prior to screening visit:\n\n  * Fibrates (e.g., fenofibrate, clofibrate, gemfibrozil)\n  * Prescription-strength omega-3 fatty acids (e.g., Lovaza®, Vascepa®)\n* Known, documented history, at the time of screening, of any of the following medical conditions:\n\n  * Pancreatic pathology\n  * Cardiovascular diseases (N.B. uncomplicated hypertension is not exclusionary)\n  * Chronic kidney disease, Stage 3 or higher (estimated glomerular filtration rate \\\u003C 60 mL min-1 1.73 m-2), of any cause\n  * Advanced or severe liver disease (including fibrosis scores of F3-F4 on screening VCTE)\n  * Gallstone disease\n  * Chronic viral illness\n  * Malabsorptive conditions (active)\n  * Active seizure disorder (including controlled with antiepileptic drugs)\n  * Psychiatric diseases causing functional impairment and\u002For requiring use of anti-dopaminergic antipsychotic drugs associated with significant weight gain\u002Fmetabolic dysfunction (e.g., clozapine, olanzapine), monoamine oxidase inhibitors, tricyclic antidepressants, or lithium\n  * Known adrenal disease\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\n* Clinical concern for increased risk of volume overload, including due to medications and\u002For heart\u002Fliver\u002Fkidney problems, as listed above\n* Clinical concern for increased risk of hypokalemia, including low potassium on screening labs (i.e., below lower limit of normal), use of certain medications, or any medical conditions listed above\n* Use of certain medications currently or within 30 d prior to screening:\n\n  * Prescribed medications used for any of the indications in the preceding list of excluded conditions, or their use within 30 d prior to screening, except allowances for:\n  * Use of drugs prescribed for indications other than the exclusionary diagnoses\u002Fpurposes listed above, e.g., antiepileptic drugs used for non-seizure indications, ACEi (angiotensin-converting enzyme inhibitor) \u002F ARB (angiotensin receptor blocker) used for uncomplicated hypertension rather than for congestive heart failure, etc. Note, as above, that antidiabetic drugs except metformin within 30 days of screening are excluded.\n  * Loop diuretics (furosemide, torsemide, ethacrynic acid)\n  * 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\n  * Fludrocortisone\n  * Beta blockers or non-dihydropyridine calcium channel blockers (verapamil or diltiazem)\n* 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\n* Clinical concern for alcohol overuse, including recent documented history during screening and\u002For participant report of regularly consuming more than 2 drinks per day for males or 1 drink per day for females.\n* Positive urine drug screen, with exceptions for:\n\n  * Lawfully prescribed medications\n  * Marijuana\u002FTHC positivity, provided that the participant agrees not to use it during the same period that they will abstain from alcohol\n* History of severe infection or ongoing febrile illness within 14 days of screening\n* Any other disease, 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.\n* Known allergy\u002Fhypersensitivity to any component of the medicinal product formulations, foods (including soy, dairy, peanuts, tree nuts, or egg), IV infusion equipment, plastics, adhesive or silicone, history of infusion site reactions with IV administration of other medicines, or ongoing clinically important allergy\u002Fhypersensitivity as judged by the investigator.\n* Concurrent enrollment in another clinical study of any investigational drug therapy within 30 days prior to screening or within 5 half-lives of an investigational agent, whichever is longer.","ALL","18 Years","65 Years",{"count":147,"type":148},36,"ESTIMATED","INTERVENTIONAL",[151],"PHASE1","This is a single-center, prospective, randomized, controlled (crossover) clinical study designed to investigate the impact of lowering insulin levels on hepatic glucose production (HGP) vs de novo lipogenesis (DNL) in people with insulin resistance. The investigators will recruit participants with a history of overweight\u002Fobesity and evidence of insulin resistance (i.e., fasting hyperinsulinemia plus prediabetes and\u002For impaired fasting glucose and\u002For Homeostasis Model Assessment of Insulin Resistance \\[HOMA-IR\\] score \\>=2.73), and with evidence of metabolic dysfunction-associated steatotic liver disease (MASLD). Participants will undergo two pancreatic clamp procedures -- one in which serum insulin levels are maintained near hyperinsulinemic baseline (Maintenance Hyperinsulinemia or \"MH\" Protocol) and the other in which serum insulin levels are lowered by 50% (Reduction toward Euinsulinemia or \"RE\" Protocol). In both clamps the investigators will use stable-isotope tracers to monitor hepatic glucose and triglyceride metabolism. The primary outcome will be the impact of steady-state clamp insulinemia on HGP vs DNL.",[154,155,156,157,158,159],"Insulin Resistance","Hyperinsulinemia","Metabolic Dysfunction Associated Steatotic Liver Disease","Non-Alcoholic Fatty Liver Disease","Prediabetic State","Obesity",[161,155,162,163,164],"Insulin resistance","Diabetes","Non-alcoholic fatty liver disease","Metabolic dysfunction associated steatotic liver disease","NOT_YET_RECRUITING","2026-02-04",{"date":168,"type":169},"2026-02-06","ACTUAL",{"date":171,"type":148},"2027-01-01",{"date":173,"type":148},"2029-02-28",{"name":5,"class":6},1]