Evaluating Glial Acetate Metabolism as a Biomarker of Hypoglycemic Complications in Diabetic Patients (GLEAM)

Evaluating Glial Acetate Metabolism as a Biomarker of Hypoglycemic Complications in Diabetic Patients: A Proof of Concept Study.

A recent pilot study, GLIMPSE (NCT02690168), was recently completed which demonstrated that the rate of glial acetate metabolism (GAM) is closely associated with susceptibility to fasting-induced hypoglycemia in healthy adults. Insulin-induced hypoglycemia is a common complication of diabetes treatment and is a major barrier to the maintenance of healthy glucose levels in individuals with diabetes. The primary purpose of the study is to test the proof-of-concept that there is an association between the rate of GAM and susceptibility to insulin-induced hypoglycemia. In order to observe such a relationship the rate of GAM will be measured in a patient population known to frequently experience hypoglycemia, i.e., individuals with type 1 diabetes mellitus (T1DM).

Study Overview

• Status: Completed
• Conditions: Hypoglycemia; Diabetes
• Intervention / Treatment: Other: 13C-MRS procedure/Acetate infusion; Device: Continuous glucose monitoring

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808-4124
      • Pennington Biomedical Research Center
    • New Orleans, Louisiana, United States, 70112
      • Tulane Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female
• Ages 18-40 years
• Diagnosed with type 1 diabetes with positive antibodies or dependent on insulin therapy
• HbA1c of ≤8.5%
• Modified Clarke's Hypoglycemia Questionnaire score of 12-24
• Willing to participate in continuous glucose monitoring (CGM)

Exclusion Criteria:

• Contraindication to MRI
• Consume >10 alcoholic drinks/week
• Current use of CGM
• Current use of insulin pump
• Current use of any diabetes medication other than insulin, e.g. SGLT1/2 inhibitors.
• Current use of steroids, e.g. cortisone, and prednisone.
• History of chronic smoking or have quit less than 10 years ago
• History of cancer in the past 5 years (individuals with basal cell or squamous cell skin cancer would be allowed)
• History of seizures
• Significant, cardiac, vascular, pulmonary, gastrointestinal, neurologic, hematologic, rheumatologic, or psychiatric disease
• Significant liver disease as defined as more than twice the upper limit of normal for liver enzymes
• Significant renal disease as defined as a estimated glomerular filtration rate less than 30
• Pregnant, planning to become pregnant, or breastfeeding
• Have been hospitalized or treated in the past 3 months for severe hypoglycemia
• 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

Other: Arm 1; Participants will have there glial acetate metabolism assessed via 13C MRS at baseline and then again 14 days later. Participants will wear blinded continuous glucose monitoring devices for ~4 weeks.

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.; Device: Continuous glucose monitoring; Participants will wear blinded continuous glucose monitoring devices (dexcom, G6) for approximately 4 weeks. Sensors will be replaced every 7-10 days.; Other Names: CGM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in percent 13C enrichment of bicarbonate measured via carbon-13 magnetic resonance spectroscopy (13C-MRS)	Once at Study Visit 1 day and 1 day at Study Visit 3, 14 days apart

Collaborators and Investigators

• Sponsor: Pennington Biomedical Research Center

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2020
• Primary Completion (Actual): March 29, 2022
• Study Completion (Actual): May 4, 2022

Study Registration Dates

• First Submitted: January 16, 2020
• First Submitted That Met QC Criteria: June 11, 2020
• First Posted (Actual): June 12, 2020

Study Record Updates

• Last Update Posted (Estimate): March 9, 2023
• Last Update Submitted That Met QC Criteria: March 7, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hypoglycemia
• Other Study ID Numbers: PBRC 2018-060

Drug and device information, study documents

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