Recurrent Hypoglycemia in Type 1 Diabetes (Aim 1)

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

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.

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.

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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.

Eligibility Criteria

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

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

Contacts and Locations

Contacts

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

Locations

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

Investigators

• Principal Investigator: Elizabeth R Seaquist, MD; University of Minnesota

More Information

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT03410277
• Other Study ID Numbers: MED-2017-26317
• First Posted: January 25, 2018
• Last Update Posted: September 21, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases