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

Primary Purpose

Hyperglycaemia (Diabetic)

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Insulin
exercise
Dietary counseling
Sponsored by
Yale University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hyperglycaemia (Diabetic)

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 15 Type 2 DM subjects with HbA1C > 7.5%
  • 15 Type 1 DM subjects with HbA1C > 7.5%
  • Age 18-60
  • BMI ≥18 kg/m2
  • Weight ≤ 285 pounds

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,
  • 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

Sites / Locations

  • The Anylan Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

type 2 diabetes mellitus

type 1 diabetes mellitus

Arm Description

Subjects with type 2 diabetes on insulin.

Subjects with type 1 diabetes on insulin.

Outcomes

Primary Outcome Measures

Change in HbA1c Levels
HbA1c levels measured by MRS scanning during a hyperglycaemic clamp. Result reported is the mean decrease in HbA1C. A decrease in HbA1c indicates improvement in brain glucose levels.

Secondary Outcome Measures

Gluthathione
baseline MRS scan to measure gluthathione
Gluthathione
MRS scan to measure gluthathione
Plasma Glucose
MRS scan to measure plasma glucose
Plasma Glucose
MRS scan to measure plasma glucose
Plasma Fructose
MRS scan to measure plasma fructose
Plasma Fructose
MRS scan to measure plasma fructose
Plasma Insulin
MRS scan to measure plasma insulin
Plasma Insulin
MRS scan to measure plasma insulin

Full Information

First Posted
January 11, 2018
Last Updated
January 18, 2023
Sponsor
Yale University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT03469492
Brief Title
Investigating the Role of the Polyol Pathway in the Central Nervous System Production of Fructose
Official Title
Investigating the Role of the Polyol Pathway in the Central Nervous System Production of Fructose: an Intervention Study
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
January 18, 2018 (Actual)
Primary Completion Date
March 20, 2020 (Actual)
Study Completion Date
March 20, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
To investigate whether longer-term improvement of glycemic control in poorly controlled diabetes patients with a 12-week intensified insulin treatment regimen will lead to decreased polyol pathway activity.
Detailed Description
Polyol pathway activity will decrease in diabetic individuals who undergo intensification of their insulin treatment regimens as reflected by lower baseline brain intracellular fructose levels and higher intracellular glutathione levels. Furthermore, following longer-term improved glycemic control, patients may also have down-regulation of the pathway as reflected by decreased production of intracellular fructose in response to hyperglycemic clamp.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperglycaemia (Diabetic)

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
type 2 diabetes mellitus
Arm Type
Active Comparator
Arm Description
Subjects with type 2 diabetes on insulin.
Arm Title
type 1 diabetes mellitus
Arm Type
Active Comparator
Arm Description
Subjects with type 1 diabetes on insulin.
Intervention Type
Drug
Intervention Name(s)
Insulin
Intervention Description
Insulin regimens will be adjusted on a weekly basis as needed to achieve a target blood glucose level.
Intervention Type
Behavioral
Intervention Name(s)
exercise
Intervention Description
Exercise in accordance to the guidelines established by the American Diabetes Association.
Intervention Type
Dietary Supplement
Intervention Name(s)
Dietary counseling
Intervention Description
Dietary counseling in accordance to the guidelines established by the American Diabetes Association.
Primary Outcome Measure Information:
Title
Change in HbA1c Levels
Description
HbA1c levels measured by MRS scanning during a hyperglycaemic clamp. Result reported is the mean decrease in HbA1C. A decrease in HbA1c indicates improvement in brain glucose levels.
Time Frame
Baseline and 12 weeks
Secondary Outcome Measure Information:
Title
Gluthathione
Description
baseline MRS scan to measure gluthathione
Time Frame
0 weeks
Title
Gluthathione
Description
MRS scan to measure gluthathione
Time Frame
12 weeks
Title
Plasma Glucose
Description
MRS scan to measure plasma glucose
Time Frame
0 weeks
Title
Plasma Glucose
Description
MRS scan to measure plasma glucose
Time Frame
12 weeks
Title
Plasma Fructose
Description
MRS scan to measure plasma fructose
Time Frame
0 weeks
Title
Plasma Fructose
Description
MRS scan to measure plasma fructose
Time Frame
12 weeks
Title
Plasma Insulin
Description
MRS scan to measure plasma insulin
Time Frame
0 weeks
Title
Plasma Insulin
Description
MRS scan to measure plasma insulin
Time Frame
12 weeks
Other Pre-specified Outcome Measures:
Title
Optional Hyperglycemic Clamp
Description
Hyperglycemic clamp administered to measure glucose levels. Data represented is the number of participants the clamp was used on successfully.
Time Frame
upon enrollment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 15 Type 2 DM subjects with HbA1C > 7.5% 15 Type 1 DM subjects with HbA1C > 7.5% Age 18-60 BMI ≥18 kg/m2 Weight ≤ 285 pounds 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, 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janice Hwang, MD
Organizational Affiliation
Section of Endocrinology
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Anylan Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
35247067
Citation
Sanchez-Rangel E, Gunawan F, Jiang L, Savoye M, Dai F, Coppoli A, Rothman DL, Mason GF, Hwang JJ. Reversibility of brain glucose kinetics in type 2 diabetes mellitus. Diabetologia. 2022 May;65(5):895-905. doi: 10.1007/s00125-022-05664-y. Epub 2022 Mar 5.
Results Reference
derived

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

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