Impact of Recurrent Hypoglycemia on Brain Ketone Metabolism in Type 1 Diabetes
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Cognitive Function
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Diagnostic
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Type 1 diabetes mellitus of > 5 years (C-peptide negative, age 18-60 years, on intensive insulin therapy (HbA1c <7.5%)
- •Non-diabetic volunteers, age 18-65 years that do not meet any of the exclusion criteria.
排除标准
- •Significant baseline anemia (hemoglobin <11.0 or hematocrit < 33%)
- •A history of liver cirrhosis or porto-caval shunt surgery.
- •Any contraindications for MRI scanning.
- •Subjects that follow a vegetarian diet
- •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)
- •Subjects with a history of anxiety/ panic attacks
研究组 & 干预措施
Type 1 diabetic subjects
Subjects will undergo a hyperinsulinemic-hypoglycemic clamp with a target glucose level of 55mg/dl. Once a stable glycemic state is reached, subjects will receive a bolus-continuous infusion beta-hydroxybutyrate (BHB) or infusion of a comparable volume of normal saline (placebo) to control for possible volume effects for the remainder of the study. Throughout the BHB or saline infusion cognitive function will be tested via a standardized testing battery.
干预措施: Beta-hydroxybutyrate (Drug)
Type 1 diabetic subjects
Subjects will undergo a hyperinsulinemic-hypoglycemic clamp with a target glucose level of 55mg/dl. Once a stable glycemic state is reached, subjects will receive a bolus-continuous infusion beta-hydroxybutyrate (BHB) or infusion of a comparable volume of normal saline (placebo) to control for possible volume effects for the remainder of the study. Throughout the BHB or saline infusion cognitive function will be tested via a standardized testing battery.
干预措施: Normal Saline (Other)
Healthy Subjects
Healthy control subjects will undergo a hyperinsulinemic-hypoglycemic clamp with a target glucose level of 55mg/dl. Once a stable glycemic state is reached, subjects will receive a bolus-continuous infusion beta-hydroxybutyrate (BHB) or infusion of a comparable volume of normal saline (placebo) to control for possible volume effects for the remainder of the study. Throughout the BHB or saline infusion cognitive function will be tested via a standardized testing battery.
干预措施: Beta-hydroxybutyrate (Drug)
Healthy Subjects
Healthy control subjects will undergo a hyperinsulinemic-hypoglycemic clamp with a target glucose level of 55mg/dl. Once a stable glycemic state is reached, subjects will receive a bolus-continuous infusion beta-hydroxybutyrate (BHB) or infusion of a comparable volume of normal saline (placebo) to control for possible volume effects for the remainder of the study. Throughout the BHB or saline infusion cognitive function will be tested via a standardized testing battery.
干预措施: Normal Saline (Other)
Healthy Subjects CONTROL
Healthy control subjects will undergo a hyperinsulinemic-hypoglycemic clamp with a target glucose level of 55mg/dl. Once a stable glycemic state is reached, subjects will undergo an NMR test to characterize brain metabolism under hypoglycemia.
干预措施: Normal Saline (Other)
结局指标
主要结局
Cognitive Function
时间窗: Under clamped hypoglycemia (50 min from start)
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.
次要结局
未报告次要终点