Effect of Pulsatile Hormone Administration on Insulin Action

In humans, insulin is secreted in pulses from the pancreatic beta-cells, and these oscillations help to maintain fasting plasma glucose levels within a narrow normal range. Given the fluctuations in insulin concentrations, oscillations enhance precision of control. The hyperinsulinemic euglycemic clamp test (clamp) involves a continuous infusion of insulin and is the gold standard for measuring insulin sensitivity. In this study, insulin sensitivity measured using the standard clamp will be compared with a clamp in which the same total amount of insulin as the standard clamp is infused every five minutes instead of continuously.

Study Overview

• Status: Recruiting
• Conditions: Insulin Sensitivity
• Intervention / Treatment: Other: Continuous Insulin administration during hyperinsulinemic euglycemic clamp test; Other: Pulsatile Insulin administration during hyperinsulinemic euglycemic clamp test

Detailed Description

Participants with obesity and insulin resistance completing a randomized, controlled, two-arm parallel trial (Motivate) will be enrolled in this cross-sectional study. Twelve participants from the Motivate study will return within two weeks to complete two clamp tests within a week of each other. At these clamps, the insulin will be infused continuously at a dose of 40mU/m2/min during the first clamp test and the same total amount of insulin will be infused every five minutes at the second clamp. The day following the clamps, participants will return to the clinic in a fasted state and blood will be drawn for measurement of glucose and insulin.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Candida J Rebello, Ph.D.; Phone Number: 225-763-3159; Email: Candida.Rebello@pbrc.edu
• Study Contact Backup: Name: Frank L Greenway, MD; Phone Number: 225-763-2578; Email: Frank.Greenway@pbrc.edu

Study Locations

• United States
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Recruiting
      • Pennington Biomedical Research Center
      • Contact: Candida Rebello, PhD; Phone Number: 225-763-3159; Email: Candida.Rebello@pbrc.edu
      • Contact: Sara L Goff; Phone Number: 2257630910
      • Sub-Investigator: Frank L Greenway, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Completion of the Motivate Study (NCT05649176)

Exclusion Criteria:

• Non-completion of the end-of-study hyperinsulinemic euglycemic clamp test of the Motivate study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Continuous insulin at 40mU/m2/min; Paricipants will receive insulin infused continuously during the hyperinsulinemic euglycemic clamp test of insulin sensitivity.	Other: Continuous Insulin administration during hyperinsulinemic euglycemic clamp test; Participants will receive insulin delivered continuously during the hyperinsulinemic euglycemic clamp test
Experimental: Pulsatile insulin at 40mU/m2/min; Participants will receive insulin infused every five minutes during the hyperinsulinemic euglycemic clamp test of insulin sensitivity	Other: Pulsatile Insulin administration during hyperinsulinemic euglycemic clamp test; Participants will receive insulin delivered every five minutes during the hyperinsulinemic euglycemic clamp test

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin sensitivity	Glucose infusion rate during the hyperinsulinemic euglycemic clamp test	One day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin resistance	Homeostasis Model Assessment of Insulin Resistance	24 hours

Collaborators and Investigators

• Sponsor: Pennington Biomedical Research Center
• Investigators: Principal Investigator: Candida Rebello, PhD, Pennington Biomedical Research Center

Publications and helpful links

General Publications

• Rebello CJ, Morales TS, Chuon K, Dong S, Lam VT, Purner D, Lewis S, Lakey J, Beyl RA, Greenway FL. Physiologic hormone administration improves HbA1C in Native Americans with type 2 diabetes: A retrospective study and review of insulin secretion and action. Obes Rev. 2023 Dec;24(12):e13625. doi: 10.1111/obr.13625. Epub 2023 Aug 14.

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: January 11, 2024
• First Submitted That Met QC Criteria: January 11, 2024
• First Posted (Actual): January 22, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 14, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Glucose Metabolism Disorders; Hyperinsulinism; Insulin Resistance; Physiological Effects of Drugs; Hypoglycemic Agents; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: PBRC 2023-018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No