Recurrent Hypoglycemia in Type 1 Diabetes (Aim 2)

Diabetes Mellitus, Type 1 Clinical Trial

Official title:

Measurement of Glucose Homeostasis in Human Brain by NMR: Effect of Recurrent Hypoglycemia on Type 1 Diabetes (Aim 2)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04387422
• Other study ID #: MED-2019-28365
• Status: Active, not recruiting
• Phase: N/A
• Start date: August 12, 2020
• Est. completion date: December 2028

Study information

• Verified date: May 2024
• Source: University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: December 2028
• Est. primary completion date: December 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Hypoglycemia

Intervention

Other:
• Experimental hyperglycemia
Experimental hyperglycemia with MRI

Locations

Country	Name	City	State
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	14 days
Secondary	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.	14 days
Secondary	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.	14 days
Secondary	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.	14 days
Secondary	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.	14 days
Secondary	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.	14 days