- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02471040
Brain Ketone Metabolism in Type 1 Diabetes
April 25, 2023 updated by: Yale University
Impact of Recurrent Hypoglycemia on Brain Ketone Metabolism in Type 1 Diabetes
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Interventional
Enrollment (Actual)
44
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Connecticut
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New Haven, Connecticut, United States, 06510
- Yale New Haven Hospital
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- Pregnancy
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
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 Names:
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 Names:
|
Active Comparator: 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.
|
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 Names:
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 Names:
|
Active Comparator: 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.
|
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 Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cognitive Function
Time Frame: 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.
|
Under clamped hypoglycemia (50 min from start)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 14, 2013
Primary Completion (Actual)
April 4, 2022
Study Completion (Actual)
April 4, 2022
Study Registration Dates
First Submitted
May 28, 2015
First Submitted That Met QC Criteria
June 10, 2015
First Posted (Estimate)
June 12, 2015
Study Record Updates
Last Update Posted (Actual)
April 27, 2023
Last Update Submitted That Met QC Criteria
April 25, 2023
Last Verified
April 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1208010648
- 2R01DK101984-06 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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