Brain Ketone Metabolism in Type 1 Diabetes

Yale University44 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

SINGLE

Enrollment

Conditions

Type 1 Diabetes Hypoglycemia

Interventions

Beta-hydroxybutyrateDRUG

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.

Normal SalineOTHER

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Yale New Haven Hospital

New Haven, Connecticut, United States

Outcomes

Primary Outcomes

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.

Time frame: Under clamped hypoglycemia (50 min from start)

Data from ClinicalTrials.gov

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