Investigating the Role of the Polyol Pathway in the Central Nervous System

Investigating the Role of Polyol Pathway in the Central Nervous System

Patients will undergo magnetic resonance spectroscopy (MRS) scanning to noninvasively measure intracerebral and plasma metabolite levels at baseline and following 2 and 4 hours of hyperglycemia. Subjects will also undergo a lumbar puncture at a separate occasion to assess cerebrospinal fluid levels of metabolites.

Study Overview

• Status: Completed
• Conditions: Hyperglycemia
• Intervention / Treatment: Other: Brain MRS during hyperglycemic clamp; Other: Analysis of Metabolites in cerebrospinal fluid

• Study Type: Interventional
• Enrollment (Actual): 138
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 2 DM with HbA1C treated with metformin, sulfonylurea, insulin, or combination OR age-matched, non-diabetic obese (BMI > 30 kg/m^2) OR age-matched lean, healthy control subjects (BMI < 25 kg/m^2)
• Age 18-55
• BMI 18-45 kg/m^2

Exclusion Criteria:

• Creatinine > 1.5 mg/dL
• Hgb < 10 mg/dL
• ALT > 2.5 x ULN
• Untreated thyroid disease
• Uncontrolled Hypertension
• Known Neurological Disorders
• Untreated Psychiatric Disorders
• Malignancy
• Bleeding Disorders
• Smoking
• Current or recent steroid use in last 3 months
• Illicit drug use
• Pregnancy, actively seeking pregnancy, or breastfeeding
• Inability to enter MRI/MRS

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Subjects with Type 2 Diabetes; Type 2 DM subjects with HbA1C > 7.5% treated with metformin, sulfonylurea, insulin or combination	Other: Brain MRS during hyperglycemic clamp; All patients will undergo brain MRS at baseline and following 2 and 4 hours of hyperglycemia using the clamp technique; Other: Analysis of Metabolites in cerebrospinal fluid; All patients will have the option to undergo a lumbar puncture for analysis of metabolites in cerebrospinal fluid
Active Comparator: Non-Diabetic Obese; Age-matched, non-diabetic obese (BMI > 30 kg/m^3) individuals	Other: Brain MRS during hyperglycemic clamp; All patients will undergo brain MRS at baseline and following 2 and 4 hours of hyperglycemia using the clamp technique; Other: Analysis of Metabolites in cerebrospinal fluid; All patients will have the option to undergo a lumbar puncture for analysis of metabolites in cerebrospinal fluid
Active Comparator: Lean, healthy control subjects; Age-matched, lean, healthy control subjects (BMI < 25 kkg/m^3)	Other: Brain MRS during hyperglycemic clamp; All patients will undergo brain MRS at baseline and following 2 and 4 hours of hyperglycemia using the clamp technique; Other: Analysis of Metabolites in cerebrospinal fluid; All patients will have the option to undergo a lumbar puncture for analysis of metabolites in cerebrospinal fluid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolite Measurements by MRS	metabolite levels will be measured by MRS	4 hours post hyperglycemia

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hunger Ratings	Hunger will be measured using a visual analog scale	4 hours post hyperglycemia
Satiety Ratings	Satiety will be measured using a visual analog scale	4 hours post hyperglycemia
Cognitive State	Participants will be asked to complete basic cognitive testing using the mini-mental status exam and the Montreal cognitive assessment	4 hours post hyperglycemia

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebrospinal fluid cell count	Metabolite levels will be measure in collected spinal fluid	2 weeks post MRS testing
protein levels	Metabolite levels will be measure in collected spinal fluid	2 weeks post MRS testing

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: American Diabetes Association
• Investigators: Principal Investigator: Robert Sherwin, MD, Yale University

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): May 18, 2022
• Study Completion (Actual): May 18, 2022

Study Registration Dates

• First Submitted: October 20, 2014
• First Submitted That Met QC Criteria: October 20, 2014
• First Posted (Estimate): October 23, 2014

Study Record Updates

• Last Update Posted (Actual): August 18, 2022
• Last Update Submitted That Met QC Criteria: August 15, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia
• Other Study ID Numbers: 1408014461