Diabetes Mellitus, Type 1
Conditions
Keywords
Diabetes Mellitus, Type 1, Medium Chain Fatty Acid, Hypoglycemia
Brief summary
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
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.
Interventions
DIETARY_SUPPLEMENTMedium 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.
OTHERSplenda (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.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Juvenile Diabetes Research Foundation
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immediate Verbal Memory | 90 minutes | 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. |
| Delayed Verbal Memory | 90 minutes | The highest score is 25 and the lowest score is 0. The higher scored indicate an improvement. |
| Verbal Memory Recognition | 90 minutes | The highest score is 15. The lowest score is 0. Higher scores indicate an improvement. |
| Digit Span Backward | 90 minutes | The highest score is 35. The lowest score is 0. The higher the score indicates an improvement. |
| Letter/Number Sequencing | 90 minutes | The highest score is 21. The lowest score is 0. Higher scores indicate an improvement. |
| Digit Symbol Coding | 90 minutes | The highest score is 133. The lowest score is 0. Higher scores indicate an improvement. |
| Map Search (2min) | 90 minutes | The highest score is 80. The lowest score is 0. Higher scores indicate an improvement. |
| Map Search (1min) | 90 minutes | The highest score is 80. The lowest score is 0. Higher scores indicate an improvement. |
| Telephone Search | 90 minutes | This is a ratio of how many symbols are found during a certain period of time. The highest ratio is the best result. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Number of Subjects 12 subjects started the study and 10 completed the study, however 11 subjects are reported in the baseline characteristics because one subjects withdrew before baseline data was collected. | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Wash Out Period | Lost to Follow-up | 1 | 1 |
Baseline characteristics
| Characteristic | Overall Number of Subjects |
|---|---|
| Age, Continuous | 34.8 years STANDARD_DEVIATION 8.9 |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Delayed Verbal Memory
The highest score is 25 and the lowest score is 0. The higher scored indicate an improvement.
Time frame: 90 minutes
Population: With the validation span test, a decrease in cognitive performance from euglycemia to hypoglycemia (22+/-2.3 vs 13.4+/-2.5) or a difference of 8.6 has been reported. Using this, a sample size of 12 will provide 80% power to detect a 23% (i.e. 2 unit) attenuation of the effect of hypoglycemia on cognitive performance.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Type 1 Diabetes With MCT Oil | Delayed Verbal Memory | Euglycemia | 14.82 units on a scale | Standard Error 1.25 |
| Type 1 Diabetes With MCT Oil | Delayed Verbal Memory | Hypoglycemia | 14.80 units on a scale | Standard Error 1.31 |
| Type 1 Diabetes Without MCT Oil | Delayed Verbal Memory | Euglycemia | 15.33 units on a scale | Standard Error 1.4 |
| Type 1 Diabetes Without MCT Oil | Delayed Verbal Memory | Hypoglycemia | 11.58 units on a scale | Standard Error 0.71 |
Primary
Digit Span Backward
The highest score is 35. The lowest score is 0. The higher the score indicates an improvement.
Time frame: 90 minutes
Population: With the validation span test, a decrease in cognitive performance from euglycemia to hypoglycemia (22+/-2.3 vs 13.4+/-2.5) or a difference of 8.6 has been reported. Using this, a sample size of 12 will provide 80% power to detect a 23% (i.e. 2 unit) attenuation of the effect of hypoglycemia on cognitive performance.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Type 1 Diabetes With MCT Oil | Digit Span Backward | Euglycemia | 0.60 units on a scale | Standard Error 0.05 |
| Type 1 Diabetes With MCT Oil | Digit Span Backward | Hypoglycemia | 0.58 units on a scale | Standard Error 0.05 |
| Type 1 Diabetes Without MCT Oil | Digit Span Backward | Euglycemia | 0.64 units on a scale | Standard Error 0.05 |
| Type 1 Diabetes Without MCT Oil | Digit Span Backward | Hypoglycemia | 0.54 units on a scale | Standard Error 0.05 |
Primary
Digit Symbol Coding
The highest score is 133. The lowest score is 0. Higher scores indicate an improvement.
Time frame: 90 minutes
Population: With the validation span test, a decrease in cognitive performance from euglycemia to hypoglycemia (22+/-2.3 vs 13.4+/-2.5) or a difference of 8.6 has been reported. Using this, a sample size of 12 will provide 80% power to detect a 23% (i.e. 2 unit) attenuation of the effect of hypoglycemia on cognitive performance.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Type 1 Diabetes With MCT Oil | Digit Symbol Coding | Euglycemia | 72.50 units on a scale | Standard Error 5.27 |
| Type 1 Diabetes With MCT Oil | Digit Symbol Coding | Hypoglycemia | 74.99 units on a scale | Standard Error 4.56 |
| Type 1 Diabetes Without MCT Oil | Digit Symbol Coding | Euglycemia | 74.04 units on a scale | Standard Error 4.59 |
| Type 1 Diabetes Without MCT Oil | Digit Symbol Coding | Hypoglycemia | 68.56 units on a scale | Standard Error 3.54 |
Primary
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.
Time frame: 90 minutes
Population: With the validation span test, a decrease in cognitive performance from euglycemia to hypoglycemia (22+/-2.3 vs 13.4+/-2.5) or a difference of 8.6 has been reported. Using this, a sample size of 12 will provide 80% power to detect a 23% (i.e. 2 unit) attenuation of the effect of hypoglycemia on cognitive performance.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Type 1 Diabetes With MCT Oil | Immediate Verbal Memory | Euglycemia | 15.85 units on a scale | Standard Error 0.66 |
| Type 1 Diabetes With MCT Oil | Immediate Verbal Memory | Hypoglycemia | 14.97 units on a scale | Standard Error 1.13 |
| Type 1 Diabetes Without MCT Oil | Immediate Verbal Memory | Euglycemia | 17.36 units on a scale | Standard Error 13.28 |
| Type 1 Diabetes Without MCT Oil | Immediate Verbal Memory | Hypoglycemia | 13.28 units on a scale | Standard Error 1.04 |
Primary
Letter/Number Sequencing
The highest score is 21. The lowest score is 0. Higher scores indicate an improvement.
Time frame: 90 minutes
Population: With the validation span test, a decrease in cognitive performance from euglycemia to hypoglycemia (22+/-2.3 vs 13.4+/-2.5) or a difference of 8.6 has been reported. Using this, a sample size of 12 will provide 80% power to detect a 23% (i.e. 2 unit) attenuation of the effect of hypoglycemia on cognitive performance.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Type 1 Diabetes With MCT Oil | Letter/Number Sequencing | Euglycemia | 12.04 units on a scale | Standard Error 0.81 |
| Type 1 Diabetes With MCT Oil | Letter/Number Sequencing | Hypoglycemia | 10.97 units on a scale | Standard Error 0.76 |
| Type 1 Diabetes Without MCT Oil | Letter/Number Sequencing | Euglycemia | 11.07 units on a scale | Standard Error 0.85 |
| Type 1 Diabetes Without MCT Oil | Letter/Number Sequencing | Hypoglycemia | 9.92 units on a scale | Standard Error 0.71 |
Primary
Map Search (1min)
The highest score is 80. The lowest score is 0. Higher scores indicate an improvement.
Time frame: 90 minutes
Population: With the validation span test, a decrease in cognitive performance from euglycemia to hypoglycemia (22+/-2.3 vs 13.4+/-2.5) or a difference of 8.6 has been reported. Using this, a sample size of 12 will provide 80% power to detect a 23% (i.e. 2 unit) attenuation of the effect of hypoglycemia on cognitive performance.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Type 1 Diabetes With MCT Oil | Map Search (1min) | Euglycemia | 53.11 units on a scale | Standard Error 4.16 |
| Type 1 Diabetes With MCT Oil | Map Search (1min) | Hypoglycemia | 48.42 units on a scale | Standard Error 3.19 |
| Type 1 Diabetes Without MCT Oil | Map Search (1min) | Euglycemia | 50.35 units on a scale | Standard Error 3.27 |
| Type 1 Diabetes Without MCT Oil | Map Search (1min) | Hypoglycemia | 42.94 units on a scale | Standard Error 2.31 |
Primary
Map Search (2min)
The highest score is 80. The lowest score is 0. Higher scores indicate an improvement.
Time frame: 90 minutes
Population: With the validation span test, a decrease in cognitive performance from euglycemia to hypoglycemia (22+/-2.3 vs 13.4+/-2.5) or a difference of 8.6 has been reported. Using this, a sample size of 12 will provide 80% power to detect a 23% (i.e. 2 unit) attenuation of the effect of hypoglycemia on cognitive performance.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Type 1 Diabetes With MCT Oil | Map Search (2min) | Euglycemia | 73.30 units on a scale | Standard Error 1.7 |
| Type 1 Diabetes With MCT Oil | Map Search (2min) | Hypoglycemia | 75.11 units on a scale | Standard Error 1.51 |
| Type 1 Diabetes Without MCT Oil | Map Search (2min) | Euglycemia | 75.04 units on a scale | Standard Error 1.92 |
| Type 1 Diabetes Without MCT Oil | Map Search (2min) | Hypoglycemia | 74.67 units on a scale | Standard Error 1.51 |
Primary
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.
Time frame: 90 minutes
Population: With the validation span test, a decrease in cognitive performance from euglycemia to hypoglycemia (22+/-2.3 vs 13.4+/-2.5) or a difference of 8.6 has been reported. Using this, a sample size of 12 will provide 80% power to detect a 23% (i.e. 2 unit) attenuation of the effect of hypoglycemia on cognitive performance.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Type 1 Diabetes With MCT Oil | Telephone Search | Euglycemia | 2.86 symbols/ 90 min | Standard Error 0.17 |
| Type 1 Diabetes With MCT Oil | Telephone Search | Hypoglycemia | 3.06 symbols/ 90 min | Standard Error 0.2 |
| Type 1 Diabetes Without MCT Oil | Telephone Search | Euglycemia | 3.14 symbols/ 90 min | Standard Error 0.26 |
| Type 1 Diabetes Without MCT Oil | Telephone Search | Hypoglycemia | 3.46 symbols/ 90 min | Standard Error 0.34 |
Primary
Verbal Memory Recognition
The highest score is 15. The lowest score is 0. Higher scores indicate an improvement.
Time frame: 90 minutes
Population: With the validation span test, a decrease in cognitive performance from euglycemia to hypoglycemia (22+/-2.3 vs 13.4+/-2.5) or a difference of 8.6 has been reported. Using this, a sample size of 12 will provide 80% power to detect a 23% (i.e. 2 unit) attenuation of the effect of hypoglycemia on cognitive performance.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Type 1 Diabetes With MCT Oil | Verbal Memory Recognition | Euglycemia | 13.19 units on a scale | Standard Error 0.53 |
| Type 1 Diabetes With MCT Oil | Verbal Memory Recognition | Hypoglycemia | 13.29 units on a scale | Standard Error 0.5 |
| Type 1 Diabetes Without MCT Oil | Verbal Memory Recognition | Euglycemia | 14.27 units on a scale | Standard Error 0.23 |
| Type 1 Diabetes Without MCT Oil | Verbal Memory Recognition | Hypoglycemia | 12.14 units on a scale | Standard Error 0.19 |