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

Early Phase 1

Completed

• Conditions: Hyperglycaemia (Diabetic)
• Interventions: Drug: Insulin; Behavioral: exercise; Dietary Supplement: Dietary counseling

• Registration Number: NCT03469492
• Lead Sponsor: Yale University

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.

Study Timeline

• Study First Submitted: 2018-01-11
• Study Start: 2018-01-18
• Study First Submitted QC: 2018-03-16
• Study First Posted: 2018-03-19
• Primary Completion: 2020-03-20
• Study Completion: 2020-03-20
• Results First Submitted: 2022-11-18
• Results First Submitted QC: 2023-01-18
• Results First Posted: 2023-02-02
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-01
• Last Update Posted: 2024-02-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
type 2 diabetes mellitus	Insulin	Subjects with type 2 diabetes on insulin.
type 2 diabetes mellitus	Dietary counseling	Subjects with type 2 diabetes on insulin.
type 1 diabetes mellitus	Insulin	Subjects with type 1 diabetes on insulin.
type 2 diabetes mellitus	exercise	Subjects with type 2 diabetes on insulin.
type 1 diabetes mellitus	exercise	Subjects with type 1 diabetes on insulin.
type 1 diabetes mellitus	Dietary counseling	Subjects with type 1 diabetes on insulin.

Primary Outcome Measures

Name	Time	Method
Change in HbA1c Levels	Baseline and 12 weeks	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

Name	Time	Method
Gluthathione	12 weeks	MRS scan to measure gluthathione
Plasma Insulin	12 weeks	MRS scan to measure plasma insulin
Plasma Glucose	12 weeks	MRS scan to measure plasma glucose
Plasma Fructose	12 weeks	MRS scan to measure plasma fructose

Trial Locations

Locations (1)

The Anylan Center; 🇺🇸 New Haven, Connecticut, United States