Investigating the Role of the Polyol Pathway in the Central Nervous System
Primary Purpose
Hyperglycemia
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Brain MRS during hyperglycemic clamp
Analysis of Metabolites in cerebrospinal fluid
Sponsored by
About this trial
This is an interventional basic science trial for Hyperglycemia
Eligibility Criteria
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
Sites / Locations
- Yale University
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Active Comparator
Arm Label
Subjects with Type 2 Diabetes
Non-Diabetic Obese
Lean, healthy control subjects
Arm Description
Type 2 DM subjects with HbA1C > 7.5% treated with metformin, sulfonylurea, insulin or combination
Age-matched, non-diabetic obese (BMI > 30 kg/m^3) individuals
Age-matched, lean, healthy control subjects (BMI < 25 kkg/m^3)
Outcomes
Primary Outcome Measures
Metabolite Measurements by MRS
metabolite levels will be measured by MRS
Secondary Outcome Measures
Hunger Ratings
Hunger will be measured using a visual analog scale
Satiety Ratings
Satiety will be measured using a visual analog scale
Cognitive State
Participants will be asked to complete basic cognitive testing using the mini-mental status exam and the Montreal cognitive assessment
Full Information
NCT ID
NCT02272556
First Posted
October 20, 2014
Last Updated
August 15, 2022
Sponsor
Yale University
Collaborators
American Diabetes Association
1. Study Identification
Unique Protocol Identification Number
NCT02272556
Brief Title
Investigating the Role of the Polyol Pathway in the Central Nervous System
Official Title
Investigating the Role of Polyol Pathway in the Central Nervous System
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
February 2015 (undefined)
Primary Completion Date
May 18, 2022 (Actual)
Study Completion Date
May 18, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
Collaborators
American Diabetes Association
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperglycemia
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
138 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Subjects with Type 2 Diabetes
Arm Type
Active Comparator
Arm Description
Type 2 DM subjects with HbA1C > 7.5% treated with metformin, sulfonylurea, insulin or combination
Arm Title
Non-Diabetic Obese
Arm Type
Active Comparator
Arm Description
Age-matched, non-diabetic obese (BMI > 30 kg/m^3) individuals
Arm Title
Lean, healthy control subjects
Arm Type
Active Comparator
Arm Description
Age-matched, lean, healthy control subjects (BMI < 25 kkg/m^3)
Intervention Type
Other
Intervention Name(s)
Brain MRS during hyperglycemic clamp
Intervention Description
All patients will undergo brain MRS at baseline and following 2 and 4 hours of hyperglycemia using the clamp technique
Intervention Type
Other
Intervention Name(s)
Analysis of Metabolites in cerebrospinal fluid
Intervention Description
All patients will have the option to undergo a lumbar puncture for analysis of metabolites in cerebrospinal fluid
Primary Outcome Measure Information:
Title
Metabolite Measurements by MRS
Description
metabolite levels will be measured by MRS
Time Frame
4 hours post hyperglycemia
Secondary Outcome Measure Information:
Title
Hunger Ratings
Description
Hunger will be measured using a visual analog scale
Time Frame
4 hours post hyperglycemia
Title
Satiety Ratings
Description
Satiety will be measured using a visual analog scale
Time Frame
4 hours post hyperglycemia
Title
Cognitive State
Description
Participants will be asked to complete basic cognitive testing using the mini-mental status exam and the Montreal cognitive assessment
Time Frame
4 hours post hyperglycemia
Other Pre-specified Outcome Measures:
Title
Cerebrospinal fluid cell count
Description
Metabolite levels will be measure in collected spinal fluid
Time Frame
2 weeks post MRS testing
Title
protein levels
Description
Metabolite levels will be measure in collected spinal fluid
Time Frame
2 weeks post MRS testing
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Sherwin, MD
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519
Country
United States
12. IPD Sharing Statement
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Investigating the Role of the Polyol Pathway in the Central Nervous System
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