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Brain Ketone Metabolism in Type 1 Diabetes

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ClinicalTrials.gov Identifier: NCT02471040
Recruitment Status : Recruiting
First Posted : June 12, 2015
Last Update Posted : August 21, 2018
Sponsor:
Information provided by (Responsible Party):
Yale University

Brief 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.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Hypoglycemia Drug: Beta-hydroxybutyrate Other: Normal Saline Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Supportive Care
Official Title: Impact of Recurrent Hypoglycemia on Brain Ketone Metabolism in Type 1 Diabetes
Study Start Date : November 2014
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


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.
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 Name: BHB

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.
Other Name: NaCl 0.9%

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.
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 Name: BHB

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.
Other Name: NaCl 0.9%




Primary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02471040


Contacts
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Contact: Claudia Moore 2037854707 claudia.moore@yale.edu
Contact: Jessica Leventhal, DNP, APRN (475) 331-8966 jessica.leventhal@yale.edu

Locations
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United States, Connecticut
Yale New Haven Hospital Recruiting
New Haven, Connecticut, United States, 06510
Sponsors and Collaborators
Yale University
Investigators
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Principal Investigator: Raimund Herzog, MD Yale School of Medicine

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Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT02471040     History of Changes
Other Study ID Numbers: 1208010648
First Posted: June 12, 2015    Key Record Dates
Last Update Posted: August 21, 2018
Last Verified: August 2018

Keywords provided by Yale University:
brain metabolism
cognitive function

Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases