Brain Ketone Metabolism in Type 1 Diabetes

Type 1 Diabetes Clinical Trial

Official title:

Impact of Recurrent Hypoglycemia on Brain Ketone Metabolism in Type 1 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02471040
• Other study ID #: 1208010648
• Secondary ID: 2R01DK101984-06
• Status: Completed
• Phase: Phase 1
• Start date: May 14, 2013
• Est. completion date: April 4, 2022

Study information

• Verified date: April 2023
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is designed to examine the value of infusing BHB in type 1 diabetic subjects during experimentally induced hypoglycemic episode in conjunction with testing of cognitive function. This will lay the basis for subsequent trials exploring the novel use of therapeutic doses of oral ketone formulations that are currently under commercial development, which could serve as adjunct therapies to protect the brain from hypoglycemia in type 1 diabetic subjects experiencing recurrent hypoglycemia.

Description:

Healthy controls as well as type 1 diabetic subjects will undergo a hyperinsulinemic-hypoglycemic clamp with concomitant BHB or saline (control) infusion in random order. During each experimental condition the participants will complete a battery of validated cognitive tests that are sensitive to the cognitive impairment typically caused by hypoglycemia. An additional healthy control arm was added to the study design after the initial registration as a 2 arm study, to provide imaging results of normal healthy responses to hypoglycemia.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: April 4, 2022
• Est. primary completion date: April 4, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Type 1 diabetes mellitus of > 5 years (C-peptide negative, age 18-60 years, on intensive insulin therapy (HbA1c <7.5%)

2. Non-diabetic volunteers, age 18-65 years that do not meet any of the exclusion criteria.

Exclusion Criteria:

1. Pregnancy

2. Significant baseline anemia (hemoglobin <11.0 or hematocrit < 33%)

3. A history of liver cirrhosis or porto-caval shunt surgery.

4. Any contraindications for MRI scanning.

5. Subjects that follow a vegetarian diet

6. Subjects that exercise heavily on a regular basis (i.e. marathon runners, body builders or other forms of excessive exercise as determined by the PI)

7. Subjects with a history of anxiety/ panic attacks

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Hypoglycemia
• Type 1 Diabetes

Intervention

Drug:
• Beta-hydroxybutyrate
Both healthy subjects and type 1 diabetic subjects will receive a bolus-continuous infusion of 40umol/min/kg of BHB for 5 min, followed by a 12µmol/min/kg of BHB or infusion of a comparable volume of normal saline (placebo) to control for possible volume effects for the remainder of the study.

Other:
• Normal Saline
Both healthy subjects and type 1 diabetic subjects will receive a bolus-continuous infusion of 40umol/min/kg of BHB for 5 min, followed by a 12µmol/min/kg of BHB or infusion of a comparable volume of normal saline (placebo) to control for possible volume effects for the remainder of the study.

Locations

Country	Name	City	State
United States	Yale New Haven Hospital	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
Primary	Cognitive Function	Subjects from all groups will be studied using the NIH Toolbox Cognition Battery, which includes measurements of Executive Function, Attention, Episodic Memory, Language, Processing Speed and Working Memory.	Under clamped hypoglycemia (50 min from start)