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Recurrent Hypoglycemia in Type 1 Diabetes (Aim 2)

Primary Purpose

Diabetes Mellitus, Type 1

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Experimental hyperglycemia
Sponsored by
University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Diabetes Mellitus, Type 1

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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
  • Unable to complete all study visits or procedures, as determined by the investigator

Sites / Locations

  • University of MinnesotaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

150 mg/dL

225 mg/dL

300 mg/dL

Arm Description

Hyperglycemia target of 150 mg/dL

Hyperglycemia target of 225 mg/dL

Hyperglycemia target of 300 mg/dL

Outcomes

Primary Outcome Measures

Glucose kinetics during hyperglycemic clamps before and after induction of IAH
A kinetic model of glucose transport through the blood-brain-barrier (BBB) via reversible symmetric Michaelis-Menten kinetics and irreversible utilization in brain tissue will be utilized. The kinetics of glucose transport into and utilization in the frontal cortex will be quantified using dynamic modeling to extract the Michaelis-Menten constants and the maximal rate for glucose transport and utilization. The ratio of maximal transport rate to cerebral metabolic rate of glucose will be estimated for the hypothalamus by steady-state modeling.

Secondary Outcome Measures

Antecedent glycemia concentration
Antecedent glycemia will be evaluated using continuous glucose monitors with particular attention to the percentage of time a participant is above, at, or below target of 80-180 mg/dl and to measures of glycemic variability.
Antecedent physical activity - moderate to vigorous physical activity
Antecedent physical activity and sleep will be evaluated using the data collected by the ActiGraph Link monitors. Activity counts will be set at 15-second epochs and classified into sedentary, light, moderate, and vigorous categories based on Troiano et al. cut points. Participants' average minutes engaged in moderate to vigorous physical activity levels per day will be reported.
Antecedent physical activity - light physical activity
Antecedent physical activity and sleep will be evaluated using the data collected by the ActiGraph Link monitors. Activity counts will be set at 15-second epochs and classified into sedentary, light, moderate, and vigorous categories based on Troiano et al. cut points. Participants' average minutes engaged in light physical activity per day will be reported.
Antecedent physical activity - sedentary time
Antecedent physical activity and sleep will be evaluated using the data collected by the ActiGraph Link monitors. Activity counts will be set at 15-second epochs and classified into sedentary, light, moderate, and vigorous categories based on Troiano et al. cut points. Participants' average minutes engaged in sedentary time per day will be reported.
Antecedent physical activity - energy expenditure
Antecedent physical activity and sleep will be evaluated using the data collected by the ActiGraph Link monitors. Activity counts will be set at 15-second epochs and classified into sedentary, light, moderate, and vigorous categories based on Troiano et al. cut points. Participants' average daily energy expenditure (kilocalories) will be reported.
Antecedent physical activity - sleep quality
Antecedent physical activity and sleep will be evaluated using the data collected by the ActiGraph Link monitors. Activity counts will be set at 15-second epochs and classified into sedentary, light, moderate, and vigorous categories based on Troiano et al. cut points. Participants' average sleep quality will be reported.

Full Information

First Posted
January 31, 2020
Last Updated
October 2, 2023
Sponsor
University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT04387422
Brief Title
Recurrent Hypoglycemia in Type 1 Diabetes (Aim 2)
Official Title
Measurement of Glucose Homeostasis in Human Brain by NMR: Effect of Recurrent Hypoglycemia on Type 1 Diabetes (Aim 2)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 12, 2020 (Actual)
Primary Completion Date
December 2028 (Anticipated)
Study Completion Date
December 2028 (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 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
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
150 mg/dL
Arm Type
Experimental
Arm Description
Hyperglycemia target of 150 mg/dL
Arm Title
225 mg/dL
Arm Type
Experimental
Arm Description
Hyperglycemia target of 225 mg/dL
Arm Title
300 mg/dL
Arm Type
Experimental
Arm Description
Hyperglycemia target of 300 mg/dL
Intervention Type
Other
Intervention Name(s)
Experimental hyperglycemia
Intervention Description
Experimental hyperglycemia with MRI
Primary Outcome Measure Information:
Title
Glucose kinetics during hyperglycemic clamps before and after induction of IAH
Description
A kinetic model of glucose transport through the blood-brain-barrier (BBB) via reversible symmetric Michaelis-Menten kinetics and irreversible utilization in brain tissue will be utilized. The kinetics of glucose transport into and utilization in the frontal cortex will be quantified using dynamic modeling to extract the Michaelis-Menten constants and the maximal rate for glucose transport and utilization. The ratio of maximal transport rate to cerebral metabolic rate of glucose will be estimated for the hypothalamus by steady-state modeling.
Time Frame
240 Minutes
Secondary Outcome Measure Information:
Title
Antecedent glycemia concentration
Description
Antecedent glycemia will be evaluated using continuous glucose monitors with particular attention to the percentage of time a participant is above, at, or below target of 80-180 mg/dl and to measures of glycemic variability.
Time Frame
14 days
Title
Antecedent physical activity - moderate to vigorous physical activity
Description
Antecedent physical activity and sleep will be evaluated using the data collected by the ActiGraph Link monitors. Activity counts will be set at 15-second epochs and classified into sedentary, light, moderate, and vigorous categories based on Troiano et al. cut points. Participants' average minutes engaged in moderate to vigorous physical activity levels per day will be reported.
Time Frame
14 days
Title
Antecedent physical activity - light physical activity
Description
Antecedent physical activity and sleep will be evaluated using the data collected by the ActiGraph Link monitors. Activity counts will be set at 15-second epochs and classified into sedentary, light, moderate, and vigorous categories based on Troiano et al. cut points. Participants' average minutes engaged in light physical activity per day will be reported.
Time Frame
14 days
Title
Antecedent physical activity - sedentary time
Description
Antecedent physical activity and sleep will be evaluated using the data collected by the ActiGraph Link monitors. Activity counts will be set at 15-second epochs and classified into sedentary, light, moderate, and vigorous categories based on Troiano et al. cut points. Participants' average minutes engaged in sedentary time per day will be reported.
Time Frame
14 days
Title
Antecedent physical activity - energy expenditure
Description
Antecedent physical activity and sleep will be evaluated using the data collected by the ActiGraph Link monitors. Activity counts will be set at 15-second epochs and classified into sedentary, light, moderate, and vigorous categories based on Troiano et al. cut points. Participants' average daily energy expenditure (kilocalories) will be reported.
Time Frame
14 days
Title
Antecedent physical activity - sleep quality
Description
Antecedent physical activity and sleep will be evaluated using the data collected by the ActiGraph Link monitors. Activity counts will be set at 15-second epochs and classified into sedentary, light, moderate, and vigorous categories based on Troiano et al. cut points. Participants' average sleep quality will be reported.
Time Frame
14 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 Unable to complete all study visits or procedures, as determined by the investigator
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 2)

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