Evaluating Glial Acetate Metabolism as a Biomarker of Hypoglycemic Counterregulation

Diabetes Clinical Trial

— E-VAL  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04207619
• Other study ID #: 2019-047-PBRC E-VAL
• Status: Recruiting
• Phase: N/A
• Start date: February 19, 2020
• Est. completion date: September 2024

Study information

• Verified date: August 2023
• Source: Pennington Biomedical Research Center
• Contact: Amber Dragg
• Phone: 225-763-3050
• Email: amber.dragg[@]pbrc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: September 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes
• Hypoglycemia

Intervention

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.
• 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

Locations

Country	Name	City	State
United States	Pennington Biomedical Research Center	Baton Rouge	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
Pennington Biomedical Research Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.