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Recurrent Hypoglycemia in Type 1 Diabetes (Aim 1)

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ClinicalTrials.gov Identifier: NCT03410277
Recruitment Status : Recruiting
First Posted : January 25, 2018
Last Update Posted : September 21, 2022
Information provided by (Responsible Party):
University of Minnesota

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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Other: Experimental hypoglycemia Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Measurement of Glucose Homeostasis in Human Brain by NMR: Effect of Recurrent Hypoglycemia on Type 1 Diabetes (Aim 1)
Actual Study Start Date : May 24, 2018
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: All Subjects
Experimental hypoglycemia
Other: Experimental hypoglycemia
Experimental hypoglycemia with and without MRI

Primary Outcome Measures :
  1. Neurochemical response to HG before and after induction of IAH [ Time Frame: 240 Minutes ]
    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 :
  1. Antecedent glycemia concentration [ Time Frame: 16 days ]
    The difference in antecedent glycemia concentration associated with the differences seen in the primary outcome.

  2. Antecedent physical activity [ Time Frame: 16 days ]
    The difference in antecedent physical activity associated with the differences seen in the primary outcome.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03410277

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Contact: Anjali Kumar, PA-C 612-301-7040 studydiabetes@umn.edu

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United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Elizabeth R Seaquist, MD    612-624-9176    studydiabetes@umn.edu   
Principal Investigator: Elizabeth R Seaquist, MD         
Sub-Investigator: Gulin Oz, PhD         
Sponsors and Collaborators
University of Minnesota
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Principal Investigator: Elizabeth R Seaquist, MD University of Minnesota
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Responsible Party: University of Minnesota
ClinicalTrials.gov Identifier: NCT03410277    
Other Study ID Numbers: MED-2017-26317
First Posted: January 25, 2018    Key Record Dates
Last Update Posted: September 21, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases