Reversibility of Brain Glucose Transport in Type 2 Diabetes Mellitus (T2DM)

Reversibility of Brain Glucose Transport and Metabolism in T2DM

The goal of this clinical trial is to learn about the effects of high blood glucose levels in the brain and assess if the changes seen in individuals with poorly control T2DM can be reversed with good glucose control.

The main question[s] it aims to answer are:

• To determine, whether abnormalities in brain glucose transport seen in individuals with uncontrolled diabetes, can be improved with better glucose control.
• Assess which factors, (duration of diabetes mellitus (DM) and glycemic control) contribute to changes in glucose transport

Participants will have:

• A screening visit
• placement of a continuous glucose monitor (CGM) 2 weeks before the first magnetic resonance spectroscopy (MRS) at week 0
• Additional visits/phone calls for intensification of diabetes management and nutrition visits
• Second magnetic resonance spectroscopy (MRS) at week 12

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Behavioral: Nutrition visits; Other: Intensification of diabetes regimen; Other: Continuous glucose monitor (CGM)

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elizabeth Sanchez Rangel, MD; Phone Number: 203-785-6430; Email: elizabeth.sanchezrangel@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale New Haven Hospital (YNHH) Research Unit (HRU)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 18-60
• medical history for Type 2 diabetes
• HbA1c > 7.5%, BMI ≥18 kg/m2
• Be willing to adhere to the intensification of their diabetes regimen

Exclusion Criteria:

• Creatinine > 1.5 mg/dL
• Hgb < 10 mg/dL, hematocrit of 37 % for males participants and 33 % for female participants
• ALT >3 x ULN
• untreated thyroid disease,
• uncontrolled hypertension
• known neurological disorders
• untreated psychiatric disorders
• malignancy
• bleeding disorders
• current or recent steroid use in last 3 months
• illicit drug use
• for women: pregnancy, actively seeking pregnancy, or breastfeeding
• inability to enter MRI/MRS (as per standard MRI safety guidelines).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Aim 1; Intervention before and after study with subjects with uncontrolled T2DM to measured brain glucose transport specifically in the occipital lobe during acute hyperglycemia

Behavioral: Nutrition visits; Participants will receive exercise and dietary counseling from a nutritionist and registered dietician with extensive experience with diabetes and obesity every 2 weeks during the 12 wee; Other: Intensification of diabetes regimen; Patient will meet every 2 weeks in person or have regular phone calls with an endocrinologist to review glucose control and intensification of the diabetes regimens. Will follow the general strategies outlined in the Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes.; Other: Continuous glucose monitor (CGM); Individuals with uncontrolled T2DM will be asked use a CGM during the 12 week intervention, to monitor glucose control. Target blood glucose levels will be between 80-130 mg/dl before meals and < 180 mg/dl at bedtime. Individuals not at goal with glycemic targets will undergo intensification of their regimen. Throughout the study, individuals will be contacted via telephone, email or through additional clinic visits as deemed necessary for maintenance of glycemic control.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain glucose concentration in the occipital cortex week 0	Intracerebral concentrations of glucose across the occipital cortex , as measured by MRS will be compared following hyperglycemic clamp in T2DM individuals at baseline (week0).	week 0
Brain glucose concentration in the occipital cortex week 12	Intracerebral concentrations of glucose across the occipital cortex will be compared between T2DM patients before and after 12 weeks of intensification of their diabetes management.	week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CGM metrics	Glycemic variability, time above range, time in range and time below range will be assessed by using EasyGV between groups at baseline and after 12 weeks of intervention	weeks 12

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Elizabeth Sanchez Rangel, MD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2024
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: March 6, 2023
• First Submitted That Met QC Criteria: March 8, 2023
• First Posted (Actual): March 20, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 10, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Diabetes Mellitus
• Other Study ID Numbers: 2000034676; 1K23DK132517-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No