Mechanisms for Restoration of Hypoglycemia Awareness

NCT ID: NCT03738852

Last Updated: 2025-02-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-07
• Study Completion Date: 2023-08-14

Brief Summary

To assess if using the hypoglycemic clamp and functional magnetic resonance imaging (fMRI) scanning in hypoglycemia unaware and aware T1DM patients and healthy controls have showed distinct differences in patterns of brain responses. In particular, T1DM patients who are aware of hypoglycemia (T1DM-Aware) have greater activity in sensory integration brain regions (e.g. parietal lobe and caudate nucleus) in response to hypoglycemia, whereas hypoglycemia unaware T1DM patients (T1DM-Unaware) show no detectable changes in brain reward regions during hypoglycemia.

Detailed Description

To assess the following: 1) if these differences are driven purely by recurrent hypoglycemia or by other closely linked factors (e.g. glycemic variability); 2) the molecular and metabolic mechanisms by which unawareness leads to the suppression of central nervous system (CNS) activity in the context of hypoglycemia; and 3) whether hypoglycemia avoidance using continuous glucose monitor restores central nervous system (CNS) activation and metabolism toward normal levels and offers a therapeutic approach to more effectively combat neurocognitive dysfunction associated with intensive treatment of T1DM patients.

Conditions

Type1 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Aim 3: Type 1 diabetes mellitus user unaware subjects 3 months

Continuous Glucose Monitor for 3 months duration

Group Type: EXPERIMENTAL

Continuous Glucose Monitor (CGM)

Intervention Type: DEVICE

Continuous Glucose Monitor (CGM)

Insulin

Intervention Type: DRUG

standard insulin regimen

Aim 1: Impact of hypoglycemia on brain connectivity Type 1

Healthy controls, T1 aware, and T1 unawares

Group Type: EXPERIMENTAL

Insulin

Intervention Type: DRUG

standard insulin regimen

Aim 2: Impact of hypoglycemia on brain glucose transports in Type 1

Healthy controls, T1 aware, and T1 unawares

Group Type: EXPERIMENTAL

Insulin

Intervention Type: DRUG

standard insulin regimen

Interventions

Continuous Glucose Monitor (CGM)

Continuous Glucose Monitor (CGM)

Intervention Type: DEVICE

Insulin

standard insulin regimen

Intervention Type: DRUG

Other Intervention Names

Dexcom G6

Eligibility Criteria

Inclusion Criteria

• Ages > 18 years
• Healthy, non-diabetic control or T1DM
• BMI > 18.0

Exclusion Criteria

• Creatinine > 1.5 mg/dL
• Hct < 35% for females, < 39% for males
• ALT > 2.5 X ULN
• untreated thyroid disease
• uncontrolled hypertension
• neurologic disorders
• untreated depression or change in antidepressant regimen in last 3 months
• use of any anxiolytic medications (benzodiazepine) or antipsychotic medications
• greater than 5% change in weight in last 3 months
• malignancy
• current or recent steroid use in last 3 months
• illicit drug use
• significant complications related to diabetes (peripheral neuropathy, proliferative retinopathy)
• inability to enter MRI (per standard MRI safety guidelines)
• for women: pregnancy or breastfeeding

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janice Hwang, Hwang

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale Center for Clinical Investigation (YCCI) Church Street Research Unit (CSRU)

New Haven, Connecticut, United States

Countries

United States

References

Akingbesote ND, Leitner BP, Jovin DG, Desrouleaux R, Owusu D, Zhu W, Li Z, Pollak MN, Perry RJ. Gene and protein expression and metabolic flux analysis reveals metabolic scaling in liver ex vivo and in vivo. Elife. 2023 May 23;12:e78335. doi: 10.7554/eLife.78335.

Reference Type: DERIVED

PMID: 37219930 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

2R01DK020495-42

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2000023189

Identifier Type: -

Identifier Source: org_study_id