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

Hyperglycaemia (Diabetic) Clinical Trial

Official title:

Investigating the Role of the Polyol Pathway in the Central Nervous System Production of Fructose: an Intervention Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03469492
• Other study ID #: 1602017151
• Secondary ID: 1K23DK109284-01
• Status: Completed
• Phase: Early Phase 1
• Start date: January 18, 2018
• Est. completion date: March 20, 2020

Study information

• Verified date: February 2024
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: March 20, 2020
• Est. primary completion date: March 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Hyperglycaemia (Diabetic)
• Hyperglycemia

Intervention

Drug:
• Insulin
Insulin regimens will be adjusted on a weekly basis as needed to achieve a target blood glucose level.

Behavioral:
• exercise
Exercise in accordance to the guidelines established by the American Diabetes Association.

Dietary Supplement:
• Dietary counseling
Dietary counseling in accordance to the guidelines established by the American Diabetes Association.

Locations

Country	Name	City	State
United States	The Anylan Center	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Optional Hyperglycemic Clamp	Hyperglycemic clamp administered to measure glucose levels. Data represented is the number of participants the clamp was used on successfully.	upon enrollment
Primary	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.	Baseline and 12 weeks
Secondary	Gluthathione	baseline MRS scan to measure gluthathione	0 weeks
Secondary	Gluthathione	MRS scan to measure gluthathione	12 weeks
Secondary	Plasma Glucose	MRS scan to measure plasma glucose	0 weeks
Secondary	Plasma Glucose	MRS scan to measure plasma glucose	12 weeks
Secondary	Plasma Fructose	MRS scan to measure plasma fructose	0 weeks
Secondary	Plasma Fructose	MRS scan to measure plasma fructose	12 weeks
Secondary	Plasma Insulin	MRS scan to measure plasma insulin	0 weeks
Secondary	Plasma Insulin	MRS scan to measure plasma insulin	12 weeks