NCT04387422

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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P25-P50 for not_applicable

Timeline
31mo left

Started Aug 2020

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress70%
Aug 2020Dec 2028

First Submitted

Initial submission to the registry

January 31, 2020

Completed
3 months until next milestone

First Posted

Study publicly available on registry

May 13, 2020

Completed
3 months until next milestone

Study Start

First participant enrolled

August 12, 2020

Completed
8.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2028

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2028

Last Updated

April 8, 2026

Status Verified

April 1, 2026

Enrollment Period

8.3 years

First QC Date

January 31, 2020

Last Update Submit

April 2, 2026

Conditions

Diabetes Mellitus, Type 1

Outcome Measures

Primary Outcomes (1)

  • 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.

    240 Minutes

Secondary Outcomes (6)

  • Antecedent glycemia concentration

    14 days

  • Antecedent physical activity - moderate to vigorous physical activity

    14 days

  • Antecedent physical activity - light physical activity

    14 days

  • Antecedent physical activity - sedentary time

    14 days

  • Antecedent physical activity - energy expenditure

    14 days

  • +1 more secondary outcomes

Study Arms (3)

150 mg/dL

EXPERIMENTAL

Hyperglycemia target of 150 mg/dL

Other: Experimental hyperglycemia

225 mg/dL

EXPERIMENTAL

Hyperglycemia target of 225 mg/dL

Other: Experimental hyperglycemia

300 mg/dL

EXPERIMENTAL

Hyperglycemia target of 300 mg/dL

Other: Experimental hyperglycemia

Interventions

Experimental hyperglycemiaOTHER

Experimental hyperglycemia with MRI

150 mg/dL225 mg/dL300 mg/dL

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Type 1 diabetes diagnosed on clinical or laboratory grounds
  • Diabetes duration 2 - 30 years
  • Hemoglobin A1C \<8.5%

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesAutoimmune DiseasesImmune System Diseases

Study Officials

  • Elizabeth R Seaquist, MD

    University of Minnesota

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 31, 2020

First Posted

May 13, 2020

Study Start

August 12, 2020

Primary Completion (Estimated)

December 1, 2028

Study Completion (Estimated)

December 1, 2028

Last Updated

April 8, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will not share

Locations

US(1)