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Trial record 16 of 667 for:    Recruiting, Not yet recruiting, Available Studies | "Insulins"

Regulation of Insulin Secretion by the GLP-1 Receptor

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ClinicalTrials.gov Identifier: NCT02844907
Recruitment Status : Not yet recruiting
First Posted : July 26, 2016
Last Update Posted : May 15, 2018
Sponsor:
Collaborator:
Durham VA Medical Center
Information provided by (Responsible Party):
David D'Alessio, M.D., Duke University

Brief Summary:

The purpose of this study is to determine the role of basal GLP-1 action on the β-cell response to insulin resistance. Healthy subjects will have fasting GLP-1 action determined with GLP-1r blockade before and after induction of experimental insulin resistance. We hypothesize that fasting GLP-1 action will increase to compensate for experimental insulin resistance.

The study will enroll up to 40 healthy participants and while it is anticipated that the screening blood draw will yield a number of screen failures, it is estimated that 10-15 subjects will complete the entire study protocol. Enrolled participants will be asked to complete three study visits including the consent visit and two infusion study visits that will include hyperglycemic clamp procedures with the addition of the GLP-1 receptor antagonist Exendin (9-39) to determine the fasting GLP-1 effect. Each infusion procedure will last 2 hours. Subjects will be asked to take dexamethasone daily for approximately one week between Visit-2 and Visit-3 to induce insulin resistance.

We will enroll 6-10 additional subjects as controls for effects of time and repeat testing. These individuals will have identical clamps with no dexamethasone at approximately 1 week intervals and will be determined at random by study staff.

The primary outcome for visits 2-3 will be to measure the effects of Ex-9 on fasting glucose-stimulated insulin secretion before and after experimentally induced insulin resistance. The primary experimental variable for analysis will be C-peptide during the clamp. Mean values will be compared between the period of glucose only stimulation and glucose with Ex-9. For each subject in the active treatment arm data will be analyzed using 2-way ANOVA for repeated measures using time (0-60 vs 60-120 min) and treatment (Dex vs no Dex) as the two factors. Based on our previous studies we expect a significant time effect due to Ex-9. If there is an interaction with treatment we would conclude that experimental insulin resistance influences the fasting GLP-1 effect. Data from control subjects will be analyzed identically; here we expect no interaction, indicating that the fasting GLP-1 is a stable measure. In our previous study using Ex-9 during a glucose clamp, the average coefficient of variation in insulin concentrations at the conclusion of each step in the ramp was 30%. Using this estimate of between subject variation, detecting a 20% difference between subsequent steps in the GLP-1 ramp with a power of 80% and significance level of 0.05 will require 8 subjects.


Condition or disease Intervention/treatment Phase
Insulin Secretion Drug: Exendin (9-39) Drug: Dexamethasone Other: Hyperglycemic Clamp Phase 4

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Regulation of Insulin Secretion by the GLP-1 Receptor
Estimated Study Start Date : June 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Dextrose

Arm Intervention/treatment
Experimental: Hyperglycemic clamp
During the 2-hour procedure, a variable infusion of 20% dextrose and blood glucose will be clamped at basal + 3mM.
Other: Hyperglycemic Clamp
A variable infusion of 20% dextrose will begin to clamp the blood glucose at basal +3 mM.

Experimental: Hyperglycemic clamp + Exendin (9-39)
During the 2-hour procedure, a variable infusion of 20% dextrose and blood glucose will be clamped at basal + 3mM. Participants will receive an infusion of the GLP-1 receptor antagonist Exendin (9-39) between the 60-120 minute time-points of the clamp. The amount of Ex-9 infused will be 750 pmol/kg/min for 60 minutes.
Drug: Exendin (9-39)
Upon establishing a hyperglycemic clamp (target blood glucose at basal +3 mM) Exendin (9-39) will be infused.
Other Name: Dextrose

Experimental: Dexamethasone
Subjects will be asked to take 4 mg once daily between Visit-2 and Visit-3.
Drug: Dexamethasone
Between Visit-2 and Visit-3, Dexamethasone (4 mg tablet) once daily for 5-7 days.




Primary Outcome Measures :
  1. Beta-cell sensitivity [ Time Frame: 20-30 minute infusion periods ]
    Beta-cell sensitivity for each incretin will equal the slope of the insulin secretion



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Ages Eligible for Study:   20 Years to 35 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Body Mass Index (BMI) < 25 kg/m2
  • HbA1c ≤ 5.7%
  • Ability to speak and understand English

Exclusion Criteria:

  • Rheumatoid arthritis
  • Diabetes or immediate family history of diabetes
  • Coronary artery disease
  • Congestive heart failure
  • Pulmonary disorders, including COPD and asthma
  • Malabsorptive GI disease, such as celiac disease, or gastric bypass
  • Significant hepatic disease
  • Renal insufficiency (eGFR < 60 mL/kg/min)
  • Anemia (hematocrit < 34%) as measured at screening visit
  • Pregnant females
  • Consumption of daily medications that alter glucose metabolism of GI function (glucocorticoids, psychotropics, narcotics, metoclopramide)
  • Consumption or injection of insulin
  • Apparent sensitivity to any of the study peptides as determined by the skin test

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02844907


Contacts
Contact: Lucy W Piner, MS 919-660-6781 lucy.piner@duke.edu

Sponsors and Collaborators
David D'Alessio, M.D.
Durham VA Medical Center

Responsible Party: David D'Alessio, M.D., Professor, Division Chief of Endocrinology, Duke University
ClinicalTrials.gov Identifier: NCT02844907     History of Changes
Other Study ID Numbers: Pro00070325
01992 ( Other Identifier: Durham VA Medical Center )
First Posted: July 26, 2016    Key Record Dates
Last Update Posted: May 15, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by David D'Alessio, M.D., Duke University:
Incretins
GLP-1
Exendin-9
Insulin Resistance

Additional relevant MeSH terms:
Insulin
Dexamethasone acetate
Dexamethasone
Glucagon-Like Peptide 1
BB 1101
Hypoglycemic Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Incretins