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Recruiting Phase 1 NCT07224334

NCT07224334 Role of Alpha-to-beta Cell Communication to Adapt Insulin Secretion to Insulin Resistance.

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Clinical Trial Summary
NCT ID NCT07224334
Status Recruiting
Phase Phase 1
Sponsor David D'Alessio, M.D.
Condition Diabetes (DM)
Study Type INTERVENTIONAL
Enrollment 30 participants
Start Date 2025-12-30
Primary Completion 2027-12

Trial Parameters

Condition Diabetes (DM)
Sponsor David D'Alessio, M.D.
Study Type INTERVENTIONAL
Phase Phase 1
Enrollment 30
Sex ALL
Min Age 18 Years
Max Age 60 Years
Start Date 2025-12-30
Completion 2027-12
Interventions
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/kg/minDexamethasone

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Brief Summary

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.

Eligibility Criteria

Aim 2A: 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: * Act

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