Recurrent Hypoglycemia in Type 1 Diabetes (Aim 2)

NCT ID: NCT04387422

Last Updated: 2025-04-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-12
• Study Completion Date: 2028-12-31

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.

Conditions

Diabetes Mellitus, Type 1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

150 mg/dL

Hyperglycemia target of 150 mg/dL

Group Type: EXPERIMENTAL

Experimental hyperglycemia

Intervention Type: OTHER

Experimental hyperglycemia with MRI

225 mg/dL

Hyperglycemia target of 225 mg/dL

Group Type: EXPERIMENTAL

Experimental hyperglycemia

Intervention Type: OTHER

Experimental hyperglycemia with MRI

300 mg/dL

Hyperglycemia target of 300 mg/dL

Group Type: EXPERIMENTAL

Experimental hyperglycemia

Intervention Type: OTHER

Experimental hyperglycemia with MRI

Interventions

Experimental hyperglycemia

Experimental hyperglycemia with MRI

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elizabeth R Seaquist, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

University of Minnesota

Minneapolis, Minnesota, United States

Countries

United States

Other Identifiers

MED-2019-28365

Identifier Type: -

Identifier Source: org_study_id