[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100610188":3},{"organization":4,"outcomesModule":7,"designInfo":19,"detailedDescription":28,"studyPopulation":18,"armGroups":29,"interventions":62,"overallOfficials":79,"centralContacts":83,"locations":93,"responsibleParty":112,"collaborators":116,"id":120,"slug":121,"hasResults":122,"nctId":123,"briefTitle":124,"officialTitle":125,"acronym":126,"eligibilityCriteria":127,"healthyVolunteers":128,"sex":129,"minAge":130,"maxAge":131,"enrollmentInfo":132,"targetDuration":18,"studyType":135,"phases":136,"briefSummary":138,"conditions":139,"keywords":141,"overallStatus":96,"whyStopped":18,"lastUpdateSubmitDate":146,"lastUpdatePostDateStruct":147,"startDateStruct":150,"completionDateStruct":152,"leadSponsor":154,"locationsCount":155},{"fullName":5,"class":6},"Duke University","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":18},[9],{"measure":10,"description":11,"timeFrame":12},"Insulin secretion with and without exendin-9: Aims 2A and 2B","Insulin secretion rates derived from deconvolution of C-peptide concentrations will be the primary outcome for insulin secretion. This measure will be compared within subjects in Aim 2A with the difference between the saline and exendin-9 clamps on each day used as the measure of fasting GLP-1 receptor mediated insulin secretion. Comparison of GLP-1 receptor mediated insulin secretion between the placebo and dexamethasone studies will be used to determine the effect of insulin resistance. Comparison of insulin secretion during the two sequential saline clamps in Aim 2A (revised 8\u002F2026) and Aim 2A sub-study will be used to determine a time-of-day effect of subsequent glucose clamps.\n\nInsulin secretion rates will also be compared within subjects in Aim 2B. Here the two different study days, one with saline and one with exendin-9 will be used.","4-8 weeks",[14],{"measure":15,"description":16,"timeFrame":17},"Insulin sensitivity: Aim 2B","Insulin sensitivity will be measured directly in subjects in Aim 2B during the hyperinsulinemic, euglycemic clamp. The glucose infusion rate necessary to maintain blood glucose at 6 mM divided by steady-state plasma insulin will be used as the index of insulin sensitivity.","Insulin sensitivity will be measured in subjects participating in Aim 2B during the hyperinsulinemic clamp in each of the two days of study. The two experiments will be completed in a 4-6 week period.",null,{"allocation":20,"interventionModel":21,"interventionModelDescription":22,"primaryPurpose":23,"observationalModel":18,"timePerspective":18,"maskingInfo":24},"NON_RANDOMIZED","PARALLEL","Subjects in Aim 2A will have paired, single-day experiments and a single-day control experiment performed within 6-8 weeks. Each subject in Aim 2B will have paired, single-day experiments performed within 4-6 weeks.","BASIC_SCIENCE",{"masking":25,"maskingDescription":18,"whoMasked":26},"SINGLE",[27],"PARTICIPANT","Subjects will undergo screening for medical history, medication usage, and blood work; those who qualify will be offered participation. Study participation will last approximately 4-8 weeks depending on the study protocol enrolled and appointment availability.\n\nAim 2A (Aim 1 of the protocol): Each participant will have two 5-hour hyperglycemic clamp procedures to test the effect of fasting glucagon-like peptide 1 (GLP-1) action before and after experimental insulin resistance. The effect of endogenous proglucagon peptides (glucagon and GLP-1) to stimulate insulin secretion will be determined by blockade of the GLP-1 receptor with the antagonist exendin-9 (Ex-9) during glucose infusions. Insulin secretion experiments will be repeated before and after induction of insulin resistance. To induce insulin resistance, subjects will take dexamethasone, a synthetic glucocorticoid that has been shown in published studies and in a pilot study by our group to reduce insulin sensitivity by \\~30%.\n\nEffective following a protocol revision in August 2026, participants in Aim 2A will also complete a third study visit that consists of two identical, sequential hyperglycemic clamps to evaluate time-of-day effects on insulin response independent of Ex-9. This protocol revision is a result of observations from the Aim 2A sub-study.\n\nAim 2A sub-study (Aim 1a of the protocol): Implemented in July 2026, a small subset of participants completed a single study visit to undergo two identical, sequential hyperglycemic clamps to examine potential time-of-day effects on glucose-stimulated insulin secretion.\n\nAim 2B (Aim 2 of the protocol): This study will recruit non-diabetic subjects with obesity. They will be studied on two occasions using a 4.5-hour procedure with a hyperglycemic clamp to measure insulin secretion, followed by a hyperinsulinemic, euglycemic clamp to measure insulin sensitivity. This procedure will be done 2 times, once with saline infused during hyperglycemia as a control, and once with exendin-9 given during hyperglycemia to determine the role of GLP-1 receptor action.",[30,38,42,46,50,54,58],{"label":31,"type":32,"description":33,"interventionNames":34},"2A [revised 8\u002F2026]: Glucose-stimulated insulin secretion with and without GLP-1 receptor blockade","EXPERIMENTAL","Aim 2A \\[revised AUG 2026\\]: Each subject will have a 5 hr experiment with sequential hyperglycemic clamps separated by a 90-minute washout. Plasma glucose will be increased with an intravenous (IV) infusion of 20% dextrose and maintained at \\~140 mg\u002FdL for 90 minutes. Following the washout, a second, identical hyperglycemic clamp will be performed. Subjects will receive an infuson of saline during the first clamp and receive exendin-9 (600 pmol\u002Fkg\u002Fmin) during the second clamp. Intervention: The interventions here are the experimental hyperglycemia with and without exendin-9.",[35,36,37],"Drug: Exendin-9 is a 30 amino acid peptide that is an established competitive antagonist of the GLP-1 receptor. Subjects will receive exendin-9 by intravenous infusion at a rate of 600 pmol\u002Fkg\u002Fmin","Drug: Dexamethasone","Drug: Dextrose 20% solution",{"label":39,"type":32,"description":40,"interventionNames":41},"Aim 2A [revised 8\u002F2026]: Sequential glucose-stimulated insulin secretion","Aim 2A \\[revised AUG 2026\\]: Each subject will have a 5 hr experiment with sequential hyperglycemic clamps separated by a 90-minute washout. Plasma glucose will be increased with an intravenous (IV) infusion of 20% dextrose and maintained at \\~140 mg\u002FdL for 90 minutes. Following the washout, a second, identical hyperglycemic clamp will be performed. Subjects will receive an infusion of saline during both clamps and the procedure will align with the temporal pattern applied during all procedures in Aim 2A. Experiment: The experiment in this arm is the examination of potential time of day effects on glucose-stimulated insulin secretion.",[37],{"label":43,"type":32,"description":44,"interventionNames":45},"2A [discont'd 8\u002F2026]: Glucose-stimulated insulin secretion with and without GLP-1 receptor blockade","Aim 2A \\[discontinued AUG 2026\\]: Each subject will have a 5 hr experiment with sequential hyperglycemic clamps separated by a 90-minute washout. Plasma glucose will be increased with an intravenous (IV) infusion of 20% dextrose and maintained stable at \\~140 mg\u002FdL for 90 minutes. Following the washout, a second, identical hyperglycemic clamp will be performed. Subjects will receive either saline or exendin-9 (600 pmol\u002Fkg\u002Fmin) during the clamps; in 10 subjects the saline\u002Fclamp will be first and in 10 subjects the exendin-9\u002Fclamp will be first; this will be assigned in alternating order as individuals are enrolled. Intervention: The interventions here are the experimental hyperglycemia with and without exendin-9.",[35,37],{"label":47,"type":32,"description":48,"interventionNames":49},"2A: Glucose-stimulated insulin secretion with\u002Fwithout GLP-1 receptor blockade and insulin resistance","Aim 2A: Subjects will be treated with 6 mg dexamethasone once daily for 7 days to induce insulin resistance before repeating the 5 hr glucose clamp study. The infusion of glucose with saline and exendin-9 will be performed identically to the first study. Intervention: The intervention in this arm is the induction of insulin resistance with dexamethasone treatment.",[35,37],{"label":51,"type":32,"description":52,"interventionNames":53},"2B: Glucose-stimulated insulin secretion and insulin sensitivity","Aim 2B: Each subject will have a 4.5 hr experiment with a 90-minute hyperglycemic clamp at a level of 2.5 mM above fasting glucose followed by a 60-minute gradual reduction in glucose infusion that leads to a 90-minute hyperinsulinemic (80 units\u002Fmeter2 Body Surface Area\u002Fminute), euglycemic clamp at a level of 6 mM.",[37],{"label":55,"type":32,"description":56,"interventionNames":57},"2B: Glucose-stimulated insulin secretion with GLP-1 receptor blockade and insulin sensitivity","Aim 2B: Subjects will receive an infusion of exendin-9 (600 pmol\u002Fkg\u002Fmin) or saline during the 90-minute hyperglycemic clamp period of the procedure. Subjects receiving exendin-9 during their first procedure will receive saline during their second procedure and vice versa; in 10 subjects the saline\u002Fclamp will be administered first and in 10 subjects the exendin-9\u002Fclamp will be administered first; this will be assigned in alternating order as individuals are enrolled. The hyperinsulinemic, euglycemic clamp during the second portion of the procedure will be conducted identically to the control arm.\n\nIntervention: The intervention in this study is the administration of exendin-9 during experimental hyperglycemia.",[35,37],{"label":59,"type":32,"description":60,"interventionNames":61},"Aim 2A sub-study [discont'd 8\u002F2026]: Sequential glucose-stimulated insulin secretion","Aim 2A control sub-study \\[discontinued AUG 2026\\]: Each subject will have a 5 hr experiment with sequential hyperglycemic clamps separated by a 90-minute washout. Plasma glucose will be increased with an intravenous (IV) infusion of 20% dextrose and maintained at \\~140 mg\u002FdL for 90 minutes. Following the washout, a second, identical hyperglycemic clamp will be performed. Subjects will receive an infusion of saline during both clamps and the procedure will align with the temporal pattern applied during all procedures in Aim 2A. Experiment: The experiment in this arm is the examination of potential time of day effects on glucose-stimulated insulin secretion.",[37],[63,68,72,76],{"type":64,"name":65,"description":66,"armGroupLabels":67,"otherNames":18},"DRUG","Exendin-9 is a 30 amino acid peptide that is an established competitive antagonist of the GLP-1 receptor. Subjects will receive exendin-9 by intravenous infusion at a rate of 600 pmol\u002Fkg\u002Fmin","Subjects in Aim 2A will receive exendin-9 on two experimental days; Subjects in Aim 2B will receive exendin-9 on one of their two experimental days.",[43,31,47,55],{"type":64,"name":69,"description":70,"armGroupLabels":71,"otherNames":18},"Dexamethasone","Dexamethasone 6 mg daily; administered for 7 days leading up to the second exendin-9 experiment in Aim 2A",[31],{"type":64,"name":73,"description":74,"armGroupLabels":75,"otherNames":18},"Dextrose 20% solution","Administered intravenously to maintain a stable blood glucose level of basal + 2.5 mM",[43,31,47,51,55,39,59],{"type":64,"name":73,"description":77,"armGroupLabels":78,"otherNames":18},"Administered intravenously to maintain a stable blood glucose level of 6.0 mM",[51,55],[80],{"name":81,"affiliation":5,"role":82},"David D'Alessio, MD","PRINCIPAL_INVESTIGATOR",[84,89],{"name":85,"role":86,"phone":87,"phoneExt":18,"email":88},"Johanna Johnson, MS","CONTACT","919-660-6766","johanna.johnson@duke.edu",{"name":90,"role":86,"phone":91,"phoneExt":18,"email":92},"Alyssa Sudnick, MS","919-660-6769","alyssa.sudnick@duke.edu",[94],{"facility":95,"status":96,"city":97,"state":98,"zip":99,"country":100,"countryCode":101,"cosmosGeoPoint":102,"geoPoint":107,"contacts":108},"Duke Center for Living","RECRUITING","Durham","North Carolina","27705","United States","US",{"type":103,"coordinates":104},"Point",[105,106],-78.89862,35.99403,{"lat":106,"lon":105},[109,110,111],{"name":85,"role":86,"phone":87,"phoneExt":18,"email":88},{"name":90,"role":86,"phone":91,"phoneExt":18,"email":92},{"name":81,"role":82,"phone":18,"phoneExt":18,"email":18},{"type":113,"investigatorFullName":114,"investigatorTitle":115,"investigatorAffiliation":5,"oldNameTitle":18,"oldOrganization":18},"SPONSOR_INVESTIGATOR","David D'Alessio, M.D.","Professor of Medicine Duke University, Director Division of Endocrinology",[117],{"name":118,"class":119},"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","NIH","100610188","phase-1-role-of-alpha-to-beta-cell-communication-to-adapt-insulin-secretion-to-insulin-resistance-100610188",false,"NCT07224334","Role of Alpha-to-beta Cell Communication to Adapt Insulin Secretion to Insulin Resistance.","Alpha to Beta Cell Communication in Health and Disease","UPGRADE","Aim 2A and 2A sub-study: Inclusion Criteria:\n\n* Age 18-45\n* Body Mass Index (BMI) \\\u003C 27.0\n* Fasting plasma glucose of ≤ 95 mg\u002FdL or HbA1c value ≤ 5.8% as measured at screening visit\n\nExclusion Criteria:\n\n* Active medical disease: e.g. active infectious, inflammatory, neurodegenerative or mental health disorders\n* Personal history of diabetes or pancreatitis\n* Personal history of cardiac, gastrointestinal, renal or liver disease\n* Immediate family history of diabetes\n* Renal insufficiency (eGFR \\\u003C 60 mL\u002Fkg\u002Fmin)\n* Anemia (hematocrit \\\u003C 34%) as measured at screening visit\n* Pregnant females\n* Poor vein access\n* Consumption of daily medications that alter glucose metabolism of GI function (glucocorticoids, psychotropics, narcotics, metoclopramide)\n* Apparent sensitivity to the study peptide as determined by the skin test\n\nAim 2B: Inclusion Criteria:\n\n* Age 35-60\n* Body Mass Index (BMI) ≥ 27.0\n* Fasting plasma glucose of \\\u003C 126 mg\u002FdL or HbA1c value \\\u003C 6.5% as measured at screening visit\n\nExclusion Criteria:\n\n* Active medical disease: e.g. active infectious, inflammatory, neurodegenerative or mental health disorders\n* Personal history of diabetes or pancreatitis\n* Personal history of cardiac, gastrointestinal, renal or liver disease\n* Immediate family history of diabetes\n* Renal insufficiency (eGFR \\\u003C 60 mL\u002Fkg\u002Fmin)\n* AST and\u002For ALT levels \\> 3x the upper limit of the normal range\n* Anemia (hematocrit \\\u003C 34%) as measured at screening visit\n* Pregnant females\n* Poor vein access\n* Consumption of daily medications that alter glucose metabolism of GI function (glucocorticoids, psychotropics, narcotics, metoclopramide)\n* Apparent sensitivity to the study peptide as determined by the skin test",true,"ALL","18 Years","60 Years",{"count":133,"type":134},30,"ESTIMATED","INTERVENTIONAL",[137],"PHASE1","Glucagon secretion from α-cells has long been viewed as primarily a counterregulatory mechanism - e.g. an agent with a role to prevent blood sugar from decreasing to levels that compromise function. Our group, along with other researchers, have begun to identify a much more complex role for α-cells, raising questions about when and how glucagon may influence blood glucose levels. This proposal looks to detail proglucagon peptide secretion from α-cells and the impact this has on β-cell function and glucose tolerance, in preclinical studies of human islets and translational studies in human subjects. This protocol registration describes Aim 2 from this NIH grant which involves 2 study populations and separate protocols but addresses a common question. Aim 3 in the grant is focused on a separate hypothesis and will be conducted and published separately from Aim 2.",[140],"Diabetes (DM)",[142,143,144,145],"insulin secretion","insulin sensitivity","GLP-1","alpha- to beta-cell communication","2026-09-28",{"date":148,"type":149},"2026-10-01","ACTUAL",{"date":151,"type":149},"2025-12-30",{"date":153,"type":134},"2027-12",{"name":114,"class":6},1]