Evaluating Glial Acetate Metabolism as a Biomarker of Hypoglycemic Counterregulation (E-VAL)

Evaluating Glial Acetate Metabolism as a Biomarker of Hypoglycemic Counterregulation Using 13C Magnetic Resonance Spectroscopy.

Hypoglycemic complications are a major impediment to the maintenance of healthy glucose levels in persons with diabetes. The investigators recently completed a clinical pilot and feasibility study (GLIMPSE, NCT02690168), which identified a novel biomarker, glial acetate metabolism, that appears to predict the susceptibility to hypoglycemia. By providing an assay to predict hypoglycemic events and therefore diabetic complications, the development of this biomarker could significantly improve the treatment of persons with diabetes.

The goal of this study is to determine the efficacy of our biomarker for predicting susceptibility to insulin-induced hypoglycemia. In order to accomplish this goal the investigatiors will pair our 13C magnetic resonance spectroscopy procedure to assess glial acetate metabolism, developed in the GLIMPSE study, with a hyperinsulinemic-hypoglycemic clamp procedure, developed in the HYPOCLAMP study (NCT03839511). The two procedures will be separated by a three day interval. The investigators will then correlate the participants' rates of glial acetate metabolism with their neuroendocrine responses to the hypoglycemic clamp. This proof of concept study will test the hypothesis that glial acetate metabolism is inversely proportional to the neuroendocrine response to hypoglycemia, that is, as glial acetate metabolism increases the neuroendocrine response will decrease.

Study Overview

• Status: Recruiting
• Conditions: Hypoglycemia; Diabetes
• Intervention / Treatment: Other: hyperinsulinemic-hypoglycemic clamp; Other: 13C-MRS procedure/Acetate infusion

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Amber Dragg; Phone Number: 225-763-3050; Email: amber.dragg@pbrc.edu
• Study Contact Backup: Name: Bethany Gildersleeve; Phone Number: 225-763-2709; Email: Bethany.Gildersleeve@pbrc.edu

Study Locations

• United States
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808-4124
      • Recruiting
      • Pennington Biomedical Research Center
      • Contact: Department of Recruiting; Phone Number: 225-763-3000; Email: recruiters@pbrc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy male or female
• Ages 18-40 years
• BMI between 20 kg/m2 and 30 kg/m2 (±0.5 kg/m2 will be accepted)
• Medically cleared for participation in the study

Exclusion Criteria:

• Contraindication to MRI
• Consume >10 alcoholic drinks/week
• History of chronic smoking or have quit less than 10 years ago
• History of clinically diagnosed diabetes or a fasting blood glucose >126 mg/dL
• Average screening blood pressure >140/90 mmHg
• History of cardiovascular disease
• Pregnant, planning to become pregnant, or breastfeeding
• Use of medications affecting glucose metabolism, e.g., benzodiazepines, thiazide diuretics, cortisone, and prednisone.
• Use of beta-adrenergic antagonists.
• Based on the investigative team's clinical judgement, a subject may not be appropriate for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Arm 1; Participants will have their glial acetate metabolism measured by carbon-13 magnetic resonance spectroscopy as well as their neuroendocrine response to hypoglycemia 3 days later.

Other: hyperinsulinemic-hypoglycemic clamp; An intravenous catheter will be placed in an antecubital vein for infusion of insulin and glucose. A second catheter will be placed retrograde in a dorsal vein of the contra-lateral hand for blood withdrawal. The hand will be placed in a heating box or pad at 70°C for arterialization of venous blood. A primed infusion of regular insulin (120 mU/min/m2) will be initiated and continued for approximately 2 hours. Beginning 20 minutes prior to the start of the insulin infusion, arterialized venous blood glucose will be measured at 5 minute intervals via a Hemocue or YSI analyzer. Following initiation of insulin infusion, blood glucose will be allowed to fall to 50 mg/dL and then maintained at this level using a variable infusion of exogenous dextrose (20% solution). Our goal is to achieve steady-state (blood glucose stabilized at 50 +/- 5 mg/dL) within the first 45 minutes following the start of insulin infusion.; Other: 13C-MRS procedure/Acetate infusion; Glial metabolism will be measured via MRS utilizing a simultaneous intravenous infusion of 13C labeled acetate. An intravenous catheter will be placed in a vein of each arm, one to infuse 13C-acetate and the other to draw blood samples

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent 13C enrichment of bicarbonate measured via carbon-13 magnetic resonance spectroscopy (13C-MRS)	Glial acetate metabolism	Every ten minutes for 120 minutes following administration of 1-13C acetate

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum epinephrine levels	The change is serum epinephrine during the hypoglycemic clamp will be determined relative to baseline levels	epinephrine will be measured every 15 minutes for 135 minutes.

Collaborators and Investigators

• Sponsor: Pennington Biomedical Research Center
• Investigators: Principal Investigator: David McDougal, PhD, PBRC

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2020
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: December 17, 2019
• First Submitted That Met QC Criteria: December 17, 2019
• First Posted (Actual): December 23, 2019

Study Record Updates

• Last Update Posted (Actual): August 23, 2023
• Last Update Submitted That Met QC Criteria: August 22, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hypoglycemia; Physiological Effects of Drugs; Hypoglycemic Agents
• Other Study ID Numbers: 2019-047-PBRC E-VAL

Drug and device information, study documents

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