Effect of Medium Chain Fatty Acids on Cognitive Function During Acute Hypoglycemia in Patients With Type 1 Diabetes

At present, there are no therapeutic agents that can minimize severe hypoglycemia (low blood sugar) and its effects on long-term brain function. The aim of this study is to determine whether the human brain is able to use medium chain fatty acids (MCFA) and/or their metabolites as an alternative fuel source during acute hypoglycemia in patients with Type 1 Diabetes Mellitus (T1DM). The hypothesis is that medium chain fatty acids will provide a rapidly absorbed, non-carbohydrate fuel that will improve cognitive performance during episodes of hypoglycemia (low blood sugar.)

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Dietary supplement: Medium chain fatty acid (Octanoic and Decanoic acid); Other: Splenda (Placebo Control)

Detailed Description

Twelve subjects between the ages of 18 years and 55 years who have had Type 1 Diabetes Mellitus for more than five years and have had tight control of their diabetes as determined by screening blood work will be invited to participate. Each study subject will undergo two hypoglycemic clamp studies (a procedure where the blood sugar is closely regulated with intravenous insulin and glucose.) In these hypoglycemic clamp studies, cognitive testing will be performed during 90 minutes of normal blood glucose followed by 90 minutes of hypoglycemia. During the hypoglycemic period, either the MCFA or a placebo will be administered. Each subject will experience both conditions. The order in which the MCFA is given will be randomized.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 1 Diabetes Mellitus for greater than 5 years (C-peptide negative)
• Age 18-55 years
• Subject is on intensive insulin therapy resulting in a Hemoglobin A1c of less than 7.5%
• History of frequent hypoglycemic events as defined as having at least one blood glucose of less than 60 mg/dl in the last four weeks

Exclusion Criteria:

• History of hypoglycemia induced seizures
• Pregnancy
• Significant baseline anemia (hemoglobin < 11.0g/dl or hematocrit < 33%)
• A history of liver cirrhosis or porto-caval shunt surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Medium chain fatty acid (Octanoic and Decanoic acid)	Dietary supplement: Medium chain fatty acid (Octanoic and Decanoic acid); Octanoic acid(67%) and Decanoic acid (27%); MCFA 50g total at 25 minute intervals with front loading of 20g then 10g for three administrations.; Other Names: Medium Chain Triglycerides; Octanoic and Decanoic acid; Fractionated coconut oil
Placebo Comparator: Splenda (Placebo Control)	Other: Splenda (Placebo Control); Placebo drink will consist of dietary sweetener Splenda mixed in water at a concentration of 1g/100mL. An unsweetened cherry flavor Koolaid mix will be added at a concentration of 0.3g/100mL of the Splenda drink to enhance flavor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immediate Verbal Memory	Results of cognitive function in diabetic patients using tests such as digit symbol substitution (a test of memory), tests of everyday attention, telephone book searching and map searching during either administration of medium chain triglyceride oil or a control solution. The goal was to determine whether the human brain is able to use medium-chain fatty acids (MCFA) and /or their metabolites as an alternative fuel source and thus improve brain function during acute hypoglycemia in patients with type 1 diabetes. The lowest score is 0 and the highest score is 25. A higher score is an improvement.	90 minutes
Delayed Verbal Memory	The highest score is 25 and the lowest score is 0. The higher scored indicate an improvement.	90 minutes
Verbal Memory Recognition	The highest score is 15. The lowest score is 0. Higher scores indicate an improvement.	90 minutes
Digit Span Backward	The highest score is 35. The lowest score is 0. The higher the score indicates an improvement.	90 minutes
Letter/Number Sequencing	The highest score is 21. The lowest score is 0. Higher scores indicate an improvement.	90 minutes
Digit Symbol Coding	The highest score is 133. The lowest score is 0. Higher scores indicate an improvement.	90 minutes
Map Search (2min)	The highest score is 80. The lowest score is 0. Higher scores indicate an improvement.	90 minutes
Map Search (1min)	The highest score is 80. The lowest score is 0. Higher scores indicate an improvement.	90 minutes
Telephone Search	This is a ratio of how many symbols are found during a certain period of time. The highest ratio is the best result.	90 minutes

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Juvenile Diabetes Research Foundation
• Investigators: Principal Investigator: Robert Sherwin, M.D., Yale University

Study record dates

Study Major Dates

• Study Start: July 1, 2005
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: December 26, 2007
• First Submitted That Met QC Criteria: December 26, 2007
• First Posted (Estimate): January 11, 2008

Study Record Updates

• Last Update Posted (Estimate): January 22, 2015
• Last Update Submitted That Met QC Criteria: January 8, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Hypoglycemia; Diabetes Mellitus, Type 1; Medium Chain Fatty Acid
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia; Anti-Infective Agents; Antifungal Agents; Decanoic acid
• Other Study ID Numbers: DK66108b_0505000079; R37DK020495 (U.S. NIH Grant/Contract); DK20495