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

Study Overview
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Brief Summary
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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.)

Detailed Description
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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.

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

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Dietary Supplement: Medium chain fatty acid (Octanoic and Decanoic acid)
* Other: Splenda (Placebo Control)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Medium chain fatty acid (Octanoic and Decanoic acid)<br> | Dietary Supplement: Medium chain fatty acid (Octanoic and Decanoic acid)<br>* Octanoic acid(67%) and Decanoic acid (27%); MCFA 50g total at 25 minute intervals with front loading of 20g then 10g for three administrations.<br>* Other names: Fractionated coconut oil;|
| Placebo Comparator: Splenda (Placebo Control)<br> | Other: Splenda (Placebo Control)<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, Type 1, Medium Chain Fatty Acid, Hypoglycemia