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

Sponsor

Pennington Biomedical Research Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04207619

Collaborator

(none)

Enrollment

Location

Arm

36.3

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Hypoglycemia	Other: hyperinsulinemic-hypoglycemic clamp Other: 13C-MRS procedure/Acetate infusion	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Feb 19, 2020

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Percent 13C enrichment of bicarbonate measured via carbon-13 magnetic resonance spectroscopy (13C-MRS) [Every ten minutes for 120 minutes following administration of 1-13C acetate]
Glial acetate metabolism

Secondary Outcome Measures

Change in serum epinephrine levels [epinephrine will be measured every 15 minutes for 135 minutes.]
The change is serum epinephrine during the hypoglycemic clamp will be determined relative to baseline levels

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pennington Biomedical Research Center	Baton Rouge	Louisiana	United States	70808-4124

Sponsors and Collaborators

Pennington Biomedical Research Center

Investigators

Principal Investigator: David McDougal, PhD, PBRC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

David McDougal, Assistant Professor, Pennington Biomedical Research Center

ClinicalTrials.gov Identifier:

NCT04207619

Other Study ID Numbers:

2019-047-PBRC E-VAL

First Posted:

Dec 23, 2019

Last Update Posted:

Apr 19, 2022

Last Verified:

Apr 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Hypoglycemia

Hypoglycemic Agents

Study Results

No Results Posted as of Apr 19, 2022