Mechanisms for Restoration of Hypoglycemia Awareness

To assess if using the hypoglycemic clamp and functional magnetic resonance imaging (fMRI) scanning in hypoglycemia unaware and aware T1DM patients and healthy controls have showed distinct differences in patterns of brain responses. In particular, T1DM patients who are aware of hypoglycemia (T1DM-Aware) have greater activity in sensory integration brain regions (e.g. parietal lobe and caudate nucleus) in response to hypoglycemia, whereas hypoglycemia unaware T1DM patients (T1DM-Unaware) show no detectable changes in brain reward regions during hypoglycemia.

Study Overview

• Status: Completed
• Conditions: Type1 Diabetes Mellitus
• Intervention / Treatment: Device: Continuous Glucose Monitor (CGM); Drug: Insulin

Detailed Description

To assess the following: 1) if these differences are driven purely by recurrent hypoglycemia or by other closely linked factors (e.g. glycemic variability); 2) the molecular and metabolic mechanisms by which unawareness leads to the suppression of central nervous system (CNS) activity in the context of hypoglycemia; and 3) whether hypoglycemia avoidance using continuous glucose monitor restores central nervous system (CNS) activation and metabolism toward normal levels and offers a therapeutic approach to more effectively combat neurocognitive dysfunction associated with intensive treatment of T1DM patients.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale Center for Clinical Investigation (YCCI) Church Street Research Unit (CSRU)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Ages > 18 years
• Healthy, non-diabetic control or T1DM
• BMI > 18.0

Exclusion Criteria:

• Creatinine > 1.5 mg/dL
• Hct < 35% for females, < 39% for males
• ALT > 2.5 X ULN
• untreated thyroid disease
• uncontrolled hypertension
• neurologic disorders
• untreated depression or change in antidepressant regimen in last 3 months
• use of any anxiolytic medications (benzodiazepine) or antipsychotic medications
• greater than 5% change in weight in last 3 months
• malignancy
• current or recent steroid use in last 3 months
• illicit drug use
• significant complications related to diabetes (peripheral neuropathy, proliferative retinopathy)
• inability to enter MRI (per standard MRI safety guidelines)
• for women: pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aim 3: Type 1 diabetes mellitus user unaware subjects 3 months; Continuous Glucose Monitor for 3 months duration	Device: Continuous Glucose Monitor (CGM); Continuous Glucose Monitor (CGM); Other Names: Dexcom G6; Drug: Insulin; standard insulin regimen
Experimental: Aim 1: Impact of hypoglycemia on brain connectivity Type 1; Healthy controls, T1 aware, and T1 unawares	Drug: Insulin; standard insulin regimen
Experimental: Aim 2: Impact of hypoglycemia on brain glucose transports in Type 1; Healthy controls, T1 aware, and T1 unawares	Drug: Insulin; standard insulin regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain glucose levels	Brain glucose will be lower and brain activation higher in those receiving continuous glucose monitor Rx.	3 months

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Janice Hwang, Hwang, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2018
• Primary Completion (Actual): August 14, 2023
• Study Completion (Actual): August 14, 2023

Study Registration Dates

• First Submitted: November 8, 2018
• First Submitted That Met QC Criteria: November 8, 2018
• First Posted (Actual): November 13, 2018

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: 2000023189; 2R01DK020495-42 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No