Recurrent Hypoglycemia in Type 1 Diabetes (Aim 1)
Primary Purpose
Diabetes Mellitus, Type 1
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Experimental hypoglycemia
Sponsored by
About this trial
This is an interventional basic science trial for Diabetes Mellitus, Type 1
Eligibility Criteria
Inclusion Criteria:
- Type 1 diabetes diagnosed on clinical or laboratory grounds
- Diabetes duration 2 - 30 years
- Hemoglobin A1C <8.5%
Exclusion Criteria:
- Impaired awareness of hypoglycemia as determined by the Cox and Gold questionnaires
- Pregnant or plan to become pregnant during the study period
- Uncontrolled hypertension (blood pressure > 145/95 mmHg at screening)
- Evidence of autonomic neuropathy (presence of orthostatic hypotension or history of gastroparesis)
- Proliferative retinopathy
- Impaired kidney function (GFR < 45)
- History of myocardial infarction, stroke, seizures, neurosurgical procedures, major depression requiring hospitalization within the last 5 years, arrhythmias
- Current substance abuse
- Use of drugs that can alter glucose metabolism including but not limited to glucocorticoids and niacin, and excluding insulin and glucose lowering drugs used to treat diabetes, as determined by a clinician
- Inability to undergo MRI scanning, including but not limited to unable to remain still in an MRI scanner for more than 30 minutes, claustrophobia, presence of paramagnetic substances or pacemakers in body, weight over 300 lbs
Sites / Locations
- University of MinnesotaRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
All Subjects
Arm Description
Experimental hypoglycemia
Outcomes
Primary Outcome Measures
Neurochemical response to HG before and after induction of IAH
The difference in neurochemical response (GABA, glutamate, and glucose) to HG during the first clamp study compared to the neurochemical response to HG after the induction of IAH as determined by the last clamp.
Secondary Outcome Measures
Antecedent glycemia concentration
The difference in antecedent glycemia concentration associated with the differences seen in the primary outcome.
Antecedent physical activity
The difference in antecedent physical activity associated with the differences seen in the primary outcome.
Full Information
NCT ID
NCT03410277
First Posted
January 18, 2018
Last Updated
October 2, 2023
Sponsor
University of Minnesota
1. Study Identification
Unique Protocol Identification Number
NCT03410277
Brief Title
Recurrent Hypoglycemia in Type 1 Diabetes (Aim 1)
Official Title
Measurement of Glucose Homeostasis in Human Brain by NMR: Effect of Recurrent Hypoglycemia on Type 1 Diabetes (Aim 1)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 24, 2018 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will explore the cerebral mechanisms of impaired awareness of hypoglycemia (IAH) in type 1 diabetics following exposure to experimental recurrent hypoglycemia (HG). To induce IAH, patients with T1D identified to have normal awareness of hypoglycemia (NAH) will undergo three 2-hour long hypoglycemic clamps. Neurochemical profiles will be measured by high field MRS before and after induction of IAH. Subject glycemic variability for 2 weeks and activity/sleep for 1 week before each study will be monitored as all factors have been shown to alter responses to HG.
Detailed Description
The long-term goal of this project is to identify how recurrent hypoglycemia (HG) leads to the clinical syndrome of impaired awareness of hypoglycemia (IAH) in type 1 diabetes (T1D). This study will test the hypothesis that recurrent HG in T1D leads to an upregulation in brain glucose transport and alterations in glutamatergic and GABAergic tone. The investigators will use MRS methodology that permits evaluation of cerebral cortex and hypothalamus in the same session to simultaneously evaluate the cerebral correlates/mediators of impaired awareness and impaired counterregulatory hormone responses (CRR). High MR data quality and reproducibility will be ensured by using high field MR scanners and technical advances (automated voxel placement, real-time voxel position, frequency, shim updates). Continuous glucose monitoring and actigraphy will be used to chronicle glucose variability and activity/exercise/sleep in the weeks before each experiment to assess the impact of these variables on IAH.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 1
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
All Subjects
Arm Type
Experimental
Arm Description
Experimental hypoglycemia
Intervention Type
Other
Intervention Name(s)
Experimental hypoglycemia
Intervention Description
Experimental hypoglycemia with and without MRI
Primary Outcome Measure Information:
Title
Neurochemical response to HG before and after induction of IAH
Description
The difference in neurochemical response (GABA, glutamate, and glucose) to HG during the first clamp study compared to the neurochemical response to HG after the induction of IAH as determined by the last clamp.
Time Frame
240 Minutes
Secondary Outcome Measure Information:
Title
Antecedent glycemia concentration
Description
The difference in antecedent glycemia concentration associated with the differences seen in the primary outcome.
Time Frame
16 days
Title
Antecedent physical activity
Description
The difference in antecedent physical activity associated with the differences seen in the primary outcome.
Time Frame
16 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Type 1 diabetes diagnosed on clinical or laboratory grounds
Diabetes duration 2 - 30 years
Hemoglobin A1C <8.5%
Exclusion Criteria:
Impaired awareness of hypoglycemia as determined by the Cox and Gold questionnaires
Pregnant or plan to become pregnant during the study period
Uncontrolled hypertension (blood pressure > 145/95 mmHg at screening)
Evidence of autonomic neuropathy (presence of orthostatic hypotension or history of gastroparesis)
Proliferative retinopathy
Impaired kidney function (GFR < 45)
History of myocardial infarction, stroke, seizures, neurosurgical procedures, major depression requiring hospitalization within the last 5 years, arrhythmias
Current substance abuse
Use of drugs that can alter glucose metabolism including but not limited to glucocorticoids and niacin, and excluding insulin and glucose lowering drugs used to treat diabetes, as determined by a clinician
Inability to undergo MRI scanning, including but not limited to unable to remain still in an MRI scanner for more than 30 minutes, claustrophobia, presence of paramagnetic substances or pacemakers in body, weight over 300 lbs
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anjali Kumar, PA-C
Phone
612-301-7040
Email
studydiabetes@umn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elizabeth R Seaquist, MD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elizabeth R Seaquist, MD
Phone
612-624-9176
Email
studydiabetes@umn.edu
First Name & Middle Initial & Last Name & Degree
Elizabeth R Seaquist, MD
First Name & Middle Initial & Last Name & Degree
Gulin Oz, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
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Recurrent Hypoglycemia in Type 1 Diabetes (Aim 1)
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