Mechanisms for Restoration of Hypoglycemia Awareness
Primary Purpose
Type1 Diabetes Mellitus
Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Continuous Glucose Monitor (CGM)
Insulin
Sponsored by
About this trial
This is an interventional treatment trial for Type1 Diabetes Mellitus
Eligibility Criteria
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
Sites / Locations
- Yale Center for Clinical Investigation (YCCI) Church Street Research Unit (CSRU)Recruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Aim 3: Type 1 diabetes mellitus user unaware subjects 3 months
Aim 1: Impact of hypoglycemia on brain connectivity Type 1
Aim 2: Impact of hypoglycemia on brain glucose transports in Type 1
Arm Description
Continuous Glucose Monitor for 3 months duration
Healthy controls, T1 aware, and T1 unawares
Healthy controls, T1 aware, and T1 unawares
Outcomes
Primary Outcome Measures
Brain glucose levels
Brain glucose will be lower and brain activation higher in those receiving continuous glucose monitor Rx.
Secondary Outcome Measures
Full Information
NCT ID
NCT03738852
First Posted
November 8, 2018
Last Updated
February 10, 2023
Sponsor
Yale University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1. Study Identification
Unique Protocol Identification Number
NCT03738852
Brief Title
Mechanisms for Restoration of Hypoglycemia Awareness
Official Title
Mechanisms for Restoration of Hypoglycemia Awareness
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 7, 2018 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
4. Oversight
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
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type1 Diabetes Mellitus
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
Participant
Masking Description
blinded
Allocation
Randomized
Enrollment
54 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Aim 3: Type 1 diabetes mellitus user unaware subjects 3 months
Arm Type
Experimental
Arm Description
Continuous Glucose Monitor for 3 months duration
Arm Title
Aim 1: Impact of hypoglycemia on brain connectivity Type 1
Arm Type
Experimental
Arm Description
Healthy controls, T1 aware, and T1 unawares
Arm Title
Aim 2: Impact of hypoglycemia on brain glucose transports in Type 1
Arm Type
Experimental
Arm Description
Healthy controls, T1 aware, and T1 unawares
Intervention Type
Device
Intervention Name(s)
Continuous Glucose Monitor (CGM)
Other Intervention Name(s)
Dexcom G6
Intervention Description
Continuous Glucose Monitor (CGM)
Intervention Type
Drug
Intervention Name(s)
Insulin
Intervention Description
standard insulin regimen
Primary Outcome Measure Information:
Title
Brain glucose levels
Description
Brain glucose will be lower and brain activation higher in those receiving continuous glucose monitor Rx.
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Janice Hwang, MD
Phone
203-785-6222
Email
janice.hwang@yale.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janice Hwang, Hwang
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale Center for Clinical Investigation (YCCI) Church Street Research Unit (CSRU)
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519
Country
United States
Individual Site Status
Recruiting
12. IPD Sharing Statement
Learn more about this trial
Mechanisms for Restoration of Hypoglycemia Awareness
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