How alpha‑cell signals change beta‑cell insulin release during insulin resistance
Official title: Alpha to Beta Cell Communication in Health and Disease
Run by Duke University · NCT07224334 · Data updated 2026-11-12
This project tests whether blocking GLP‑1 signaling changes how alpha‑cell hormones affect insulin release in non‑diabetic adults with and without obesity, before and after short‑term insulin resistance.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Ages | 18 Years to 60 Years |
| Sex | All |
| Enrollment | 30 (estimated) |
| Sponsor | Duke University Academic / other |
| Locations | 1 site (Durham, North Carolina) |
| Status | Recruiting |
| Started | December 30, 2025 |
| Main results expected | December 2027 |
| Study ends | December 2027 |
| Registry record updated | October 1, 2026 |
| Trial ID | NCT07224334 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Non‑diabetic adults who meet the age, BMI, and glucose/A1c criteria for either arm (Aim 2A: ages 18–45, BMI <27 and normal glucose; Aim 2B: ages 35–60, BMI ≥27 and non‑diabetic) and who have no major medical conditions or interfering medications are ideal candidates.
✕Probably not a fit
People with diagnosed diabetes, pancreatitis, significant cardiac/renal/hepatic disease, pregnancy, poor venous access, or who take medications that alter glucose or gut function are excluded and unlikely to benefit from participation.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
Participants are screened for medical history, medications, and blood work and then complete one to two multi‑hour metabolic clamp visits depending on the study arm. In Aim 2A, lean adults undergo two 5‑hour hyperglycemic clamps with GLP‑1 receptor blockade (exendin‑9) before and after short‑term dexamethasone‑induced insulin resistance. In Aim 2B, adults with obesity undergo paired hyperglycemic clamps (with saline control and with exendin‑9) plus a hyperinsulinemic‑euglycemic clamp to measure insulin sensitivity. The primary measures are insulin secretion responses to glucose with and without GLP‑1 receptor blockade and changes in insulin sensitivity.
Why it matters
Potential benefit: If successful, the work could clarify how alpha‑cell peptides regulate beta‑cell insulin output and point to new targets for preventing or treating early metabolic dysfunction.
How similar studies have gone: Previous preclinical and human physiology studies using GLP‑1 receptor blockade and steroid‑induced insulin resistance have shown effects on insulin secretion, but combining exendin‑9 with paired hyperglycemic clamps before and after induced insulin resistance is a relatively novel translational approach.
Who can join: the full rules
Show full inclusion / exclusion criteria
Aim 2A and 2A sub-study: Inclusion Criteria: * Age 18-45 * Body Mass Index (BMI) \< 27.0 * Fasting plasma glucose of ≤ 95 mg/dL or HbA1c value ≤ 5.8% as measured at screening visit Exclusion Criteria: * Active medical disease: e.g. active infectious, inflammatory, neurodegenerative or mental health disorders * Personal history of diabetes or pancreatitis * Personal history of cardiac, gastrointestinal, renal or liver disease * Immediate family history of diabetes * Renal insufficiency (eGFR \< 60 mL/kg/min) * Anemia (hematocrit \< 34%) as measured at screening visit * Pregnant females * Poor vein access * Consumption of daily medications that alter glucose metabolism of GI function (glucocorticoids, psychotropics, narcotics, metoclopramide) * Apparent sensitivity to the study peptide as determined by the skin test Aim 2B: Inclusion Criteria: * Age 35-60 * Body Mass Index (BMI) ≥ 27.0 * Fasting plasma glucose of \< 126 mg/dL or HbA1c value \< 6.5% as measured at screening visit Exclusion Criteria: * Active medical disease: e.g. active infectious, inflammatory, neurodegenerative or mental health disorders * Personal history of diabetes or pancreatitis * Personal history of cardiac, gastrointestinal, renal or liver disease * Immediate family history of diabetes * Renal insufficiency (eGFR \< 60 mL/kg/min) * AST and/or ALT levels \> 3x the upper limit of the normal range * Anemia (hematocrit \< 34%) as measured at screening visit * Pregnant females * Poor vein access * Consumption of daily medications that alter glucose metabolism of GI function (glucocorticoids, psychotropics, narcotics, metoclopramide) * Apparent sensitivity to the study peptide as determined by the skin test
Where it's running
-
Duke Center for Living
Durham, North Carolina, United States Recruiting
Study contacts
- Principal investigator: David D'Alessio, MD — Duke University
- Study coordinator: Johanna Johnson, MS
- Email: johanna.johnson@duke.edu
- Phone: 919-660-6766
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.