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

Part of paid clinical trials in Durham, North Carolina.

Sponsor
David D'Alessio, M.D.
Study ID
NCT07224334
Phase
PHASE1
Status
Recruiting
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Conditions

  • Diabetes (DM)

Eligibility Criteria

Sex
ALL
Age
18 Years - 60 Years
Healthy Volunteers
Accepted

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/min — DRUG
    Subjects in Aim 2A will receive exendin-9 on both experimental days and dexamethasone for one week before their second experimental day. Subjects in Aim 2B will receive exendin-9 on one of their two experimental days.
  • Dexamethasone — DRUG
    Dexamethasone 6 mg daily

Study Details

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.

Key Dates

Start date
Dec 30, 2025
Status verified
Feb 2026
Primary completion
Dec 31, 2027
Completion
Dec 31, 2027

Study Design

Enrollment
30 participants (estimated)
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE

Arms

  • Placebo Comparator: Aim 2A: Glucose-stimulated insulin secretion with and without GLP-1 receptor blockade
    Aim 2A: Each subject will have a 5 hr experiment with sequential hyperglycemic clamps separated by a 90-minute washout. Blood glucose will be increased with an intravenous (IV) infusion of 20% dextrose and maintained stable at a level of 2.5-3.0 mM above fasting glucose for 90 minutes. Following the washout, a second, identical hyperglycemic clamp will be performed. Subjects will receive either saline or exendin-9 (600 pmol/kg/min) during the clamps; in 10 subjects the saline/clamp will be first and in 10 subjects the exendin-9/clamp will be first; the orders will be assigned randomly. Intervention: The interventions here are the experimental hyperglycemia with and without exendin-9
  • Active Comparator: Glucose stimulated insulin secretion with or without 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.
  • Placebo Comparator: Aim 2B: Glucose stimulated insulin secretion and insulin sensitivity
    Aim 2B: Each subject will have a 3-hour experiment with a 90-minute hyperglycemic clamp at a level of 2.5-3.0 mM above fasting glucose followed by a 60 minute hyperinsulinemic (80 units/meter2 Body Surface Area/minute), euglycemic clamp.
  • Active Comparator: Aim 2B: Glucose stimulated insulin secretion with GLP-1 receptor blockade and insulin sensitivity
    Aim 2B: Subjects will have an identical hyperglycemic clamp but with infusion of exendin-9 (600 pmol/kg/min). Exendin-9 infusion will be stopped before the following hyperinsulinemic clamp that will be conducted identically to the control arm. Allocation of subjects in Aim 2B to the study with and without exendin-9 will be randomized. Intervention: The intervention in this study is the administration of exendin-9 during experimental hyperglycemia.

Primary Outcome Measure

Insulin secretion [ Time Frame: Insulin secretion rates will be measured on both days of study in subjects participating in Aims 2A and 2B. Studies will be completed over a period of 4-5 weeks ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Duke Center for LivingDurhamNorth Carolina27705
Johanna Johnson, MS
[email protected]
919-660-6766
Alyssa Sudnick, MS
[email protected]
919-660-6769
David D'Alessio, MD (PRINCIPAL_INVESTIGATOR)

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Duke Center for Living· Durham, NC

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