This study aims to create evidence for the seizure-reducing effect and usefulness of medium chain triglycerides (MCT) oil, a new dietary therapy, in patients with drug-refractory epilepsy. In order to reduce the body damage and mortality of patients with intractable epilepsy, improve the quality of life, and reduce the burden of medical expenses, it is urgent to find new treatment alternatives and create evidence of usefulness. MCT oil is known to inhibit the occurrence of epilepsy as it becomes the main energy source for the brain when ingested by epileptic patients. Unlike the ketogenic diet, the MCT diet is added to the normal (everyday) diet in oil or powder form and is highly tolerated. In an RCT study on a small group of intractable epilepsy patients (11 adults) recently published by an Australian research group, seizures were prevented in 5 patients through MCT intake (0.5-1 ml/kg body weight) without dietary restrictions for 3 months. A reduction of more than 50% has been reported. Therefore, in order to create first-class evidence for a larger number of patients with intractable epilepsy, we plan to create evidence for the effect and side effects of MCT oil on reducing seizures in domestic patients with intractable epilepsy.
The main research procedures of this clinical study are as follows.
1) Recruitment and enrollment of subjects
2) Baseline epilepsy, diet, medical and neurological records investigation, seizure frequency investigation
3) Implement MCT oil or sunflower oil intake therapy
4) Blood test, pregnancy test (for women of childbearing age), seizure frequency survey during oil consumption period
4) Assessment of seizure frequency and side effects after completion of MCT oil or sunflower oil intake therapy
5) Analysis of seizure reduction effect before and after MCT oil and sunflower oil intake therapy
- Tests performed according to participation in this study: intake of MCT oil or sunflower oil, blood test (CBC, Lipid profile, Urea & Electrolytes, LFT), pregnancy test (Serum, Urine)

Treatment

MCT oil intake therapy (intervention test) and sunflower oil intake therapy (control test), which subjects received as part of the clinical trial, were evaluated to evaluate the effect of MCT oil intake on seizure reduction and possible side effects, and to compare the results. It is for the purpose.
Highlights of the arbitration include:
- After recruiting a total of 100 subjects for 5 years, randomly assigned to the intervention group/control group (before visit 2).
- All study subjects were divided into intervention oil intake group (MCT oil) and control oil intake group (sunflower oil) by random assignment
- Randomization method: In this clinical trial, "block randomization" with various block sizes is used as a method for randomizing subjects. Research nurses who are not related to this clinical trial should keep researchers participating in this study hidden in the randomization process. In addition, all placebo and MCT oil bottles are numbered and assigned to patients by this research nurse, so all researchers involved in the study remain blind.
- block randomization lists of various sizes. [MCT intake regimen > Sunflower oil intake regimen], [Sunflower oil intake regimen > MCT intake regimen] The order is randomly assigned in a 1:1 ratio within the block. The block sizes are 2, 4, 6, 8, and 10, and the size allocation is unequally allocated at a ratio of 1:5:6:4:1.

The detailed treatment protocol is as follows.
1) Baseline (Visit 1~Visit 2)
- Evaluate seizure frequency at both visit 1 and visit 2
2) Titration (Visit 2~Visit 3; 3 weeks)
- Period to determine the effective or maximum tolerated dose for reducing seizure frequency in the intervention oil intake group (MCT oil) (titration was also conducted in the control oil intake group (sunflower oil)
- Conduct baseline questionnaire test [BAI , BDI-II , QOLIE-10-P ]
- Titration procedure: In this study, the daily appropriate dose of oil consumed by the subjects was 25 to 60 ml (taken with three meals). This standard corresponds to 0.7 ml/kg of body weight or 25% of daily caloric intake. Increase the dose once every 3 days.
3) Oil intake (Visit 3~Visit 4)
- 12 weeks of oil intake therapy with a fixed dose during the titration period
- Evaluate seizure frequency for a total of 4 times from visit 3 to visit 4
- Perform follow-up questionnaire after completion of oil intake therapy [BAI, BDI-II, QOLIE-10-P]
4) Titration-off (Visit 4~Visit 5)
- Reduce the amount of oil intake for a total of 3 weeks after completing oil intake therapy
5) Wash-out (Visit 5~Visit 6)
- It is an 8-week withdrawal period to wash away the effects of previous oil intake for crossover testing (After wash-out, existing MCT (or sunflower oil) subjects proceed with sunflower oil (or MCT) oil intake process.)
6) Titration (Visit 6~Visit 7; 3 weeks)
- Period to determine the effective or maximum tolerated dose for reducing seizure frequency in the intervention oil intake group (MCT oil) (titration was also conducted in the control oil intake group (sunflower oil)
- Titration procedure: In this study, the daily appropriate dose of oil consumed by the subjects was 25 to 60 ml (taken with three meals). This standard corresponds to 0.7 ml/kg of body weight or 25% of daily caloric intake. Increase the dose once every 3 days.
7) Oil intake (Visit 7~Visit 8)
- 12 weeks of oil intake therapy with a fixed dose during the titration period
- Seizure frequency was evaluated for a total of 4 times from Visit 7 to Visit 8
8) End of visit and unblinding (Visit 8)
- Subjects completed all therapies (interventional MCT oil, control sunflower oil) on Visit 8
- Subjects were blinded at visit 8 and determined whether or not to consume Free-MCT (week 12).
- All subjects who agreed to consume Free-MCT received Free-MCT oil without a titration-off procedure for 3 weeks and then consumed MCT oil. 

Arm Label

Target Number of Participant

Arm Type

Arm Description

MCT oil intake therapy (intervention test) and sunflower oil intake therapy (control test), which subjects received as part of the clinical trial, were evaluated to evaluate the effect of MCT oil intake on seizure reduction and possible side effects, and to compare the results. It is for the purpose.
Highlights of the arbitration include:
- After recruiting a total of 100 subjects for 5 years, randomly assigned to the intervention group/control group (before visit 2).
- All study subjects were divided into intervention oil intake group (MCT oil) and control oil intake group (sunflower oil) by random assignment
- Randomization method: In this clinical trial, "block randomization" with various block sizes is used as a method for randomizing subjects. Research nurses who are not related to this clinical trial should keep researchers participating in this study hidden in the randomization process. In addition, all placebo and MCT oil bottles are numbered and assigned to patients by this research nurse, so all researchers involved in the study remain blind.
- block randomization lists of various sizes. [MCT intake regimen > Sunflower oil intake regimen], [Sunflower oil intake regimen > MCT intake regimen] The order is randomly assigned in a 1:1 ratio within the block. The block sizes are 2, 4, 6, 8, and 10, and the size allocation is unequally allocated at a ratio of 1:5:6:4:1.

The detailed treatment protocol is as follows.
1) Baseline (Visit 1~Visit 2)
- Evaluate seizure frequency at both visit 1 and visit 2
2) Titration (Visit 2~Visit 3; 3 weeks)
- Period to determine the effective or maximum tolerated dose for reducing seizure frequency in the intervention oil intake group (MCT oil) (titration was also conducted in the control oil intake group (sunflower oil)
- Conduct baseline questionnaire test [BAI , BDI-II , QOLIE-10-P ]
- Titration procedure: In this study, the daily appropriate dose of oil consumed by the subjects was 25 to 60 ml (taken with three meals). This standard corresponds to 0.7 ml/kg of body weight or 25% of daily caloric intake. Increase the dose once every 3 days.
3) Oil intake (Visit 3~Visit 4)
- 12 weeks of oil intake therapy with a fixed dose during the titration period
- Evaluate seizure frequency for a total of 4 times from visit 3 to visit 4
- Perform follow-up questionnaire after completion of oil intake therapy [BAI, BDI-II, QOLIE-10-P]
4) Titration-off (Visit 4~Visit 5)
- Reduce the amount of oil intake for a total of 3 weeks after completing oil intake therapy
5) Wash-out (Visit 5~Visit 6)
- It is an 8-week withdrawal period to wash away the effects of previous oil intake for crossover testing (After wash-out, existing MCT (or sunflower oil) subjects proceed with sunflower oil (or MCT) oil intake process.)
6) Titration (Visit 6~Visit 7; 3 weeks)
- Period to determine the effective or maximum tolerated dose for reducing seizure frequency in the intervention oil intake group (MCT oil) (titration was also conducted in the control oil intake group (sunflower oil)
- Titration procedure: In this study, the daily appropriate dose of oil consumed by the subjects was 25 to 60 ml (taken with three meals). This standard corresponds to 0.7 ml/kg of body weight or 25% of daily caloric intake. Increase the dose once every 3 days.
7) Oil intake (Visit 7~Visit 8)
- 12 weeks of oil intake therapy with a fixed dose during the titration period
- Seizure frequency was evaluated for a total of 4 times from Visit 7 to Visit 8
8) End of visit and unblinding (Visit 8)
- Subjects completed all therapies (interventional MCT oil, control sunflower oil) on Visit 8
- Subjects were blinded at visit 8 and determined whether or not to consume Free-MCT (week 12).
- All subjects who agreed to consume Free-MCT received Free-MCT oil without a titration-off procedure for 3 weeks and then consumed MCT oil. 

Arm Label

Target Number of Participant

Arm Type

Arm Description

MCT oil intake therapy (intervention test) and sunflower oil intake therapy (control test), which subjects received as part of the clinical trial, were evaluated to evaluate the effect of MCT oil intake on seizure reduction and possible side effects, and to compare the results. It is for the purpose.
Highlights of the arbitration include:
- After recruiting a total of 100 subjects for 5 years, randomly assigned to the intervention group/control group (before visit 2).
- All study subjects were divided into intervention oil intake group (MCT oil) and control oil intake group (sunflower oil) by random assignment
- Randomization method: In this clinical trial, "block randomization" with various block sizes is used as a method for randomizing subjects. Research nurses who are not related to this clinical trial should keep researchers participating in this study hidden in the randomization process. In addition, all placebo and MCT oil bottles are numbered and assigned to patients by this research nurse, so all researchers involved in the study remain blind.
- block randomization lists of various sizes. [MCT intake regimen > Sunflower oil intake regimen], [Sunflower oil intake regimen > MCT intake regimen] The order is randomly assigned in a 1:1 ratio within the block. The block sizes are 2, 4, 6, 8, and 10, and the size allocation is unequally allocated at a ratio of 1:5:6:4:1.

The detailed treatment protocol is as follows.
1) Baseline (Visit 1~Visit 2)
- Evaluate seizure frequency at both visit 1 and visit 2
2) Titration (Visit 2~Visit 3; 3 weeks)
- Period to determine the effective or maximum tolerated dose for reducing seizure frequency in the intervention oil intake group (MCT oil) (titration was also conducted in the control oil intake group (sunflower oil)
- Conduct baseline questionnaire test [BAI , BDI-II , QOLIE-10-P ]
- Titration procedure: In this study, the daily appropriate dose of oil consumed by the subjects was 25 to 60 ml (taken with three meals). This standard corresponds to 0.7 ml/kg of body weight or 25% of daily caloric intake. Increase the dose once every 3 days.
3) Oil intake (Visit 3~Visit 4)
- 12 weeks of oil intake therapy with a fixed dose during the titration period
- Evaluate seizure frequency for a total of 4 times from visit 3 to visit 4
- Perform follow-up questionnaire after completion of oil intake therapy [BAI, BDI-II, QOLIE-10-P]
4) Titration-off (Visit 4~Visit 5)
- Reduce the amount of oil intake for a total of 3 weeks after completing oil intake therapy
5) Wash-out (Visit 5~Visit 6)
- It is an 8-week withdrawal period to wash away the effects of previous oil intake for crossover testing (After wash-out, existing MCT (or sunflower oil) subjects proceed with sunflower oil (or MCT) oil intake process.)
6) Titration (Visit 6~Visit 7; 3 weeks)
- Period to determine the effective or maximum tolerated dose for reducing seizure frequency in the intervention oil intake group (MCT oil) (titration was also conducted in the control oil intake group (sunflower oil)
- Titration procedure: In this study, the daily appropriate dose of oil consumed by the subjects was 25 to 60 ml (taken with three meals). This standard corresponds to 0.7 ml/kg of body weight or 25% of daily caloric intake. Increase the dose once every 3 days.
7) Oil intake (Visit 7~Visit 8)
- 12 weeks of oil intake therapy with a fixed dose during the titration period
- Seizure frequency was evaluated for a total of 4 times from Visit 7 to Visit 8
8) End of visit and unblinding (Visit 8)
- Subjects completed all therapies (interventional MCT oil, control sunflower oil) on Visit 8
- Subjects were blinded at visit 8 and determined whether or not to consume Free-MCT (week 12).
- All subjects who agreed to consume Free-MCT received Free-MCT oil without a titration-off procedure for 3 weeks and then consumed MCT oil. 

Gender

Age

Description

(1) Adult epileptic patients between the ages of 18 and 70
(2) Patients who experienced at least 2 seizures of an eligible type (*) per month during the 2 months prior to enrollment in this clinical trial despite treatment with at least one antiepileptic drug at a clinically appropriate dose
(3) If there is no change in the history of taking antiepileptic drugs for 4 weeks prior to enrollment
(4) A person who consented to participate in the clinical trial (if voluntary consent is difficult, there must be a proxy (parent or guardian) who can consent to participate in the clinical trial on behalf of the subject)
(5) Women of childbearing potential must have a negative serum ßhCG result at the first visit and a negative urine pregnancy test prior to randomization at the second visit. Female subjects of childbearing potential must abstain from abstinence or agree to use at least one method of contraception. If the subject is using a hormonal type of birth control, they must agree to use an additional approved second method of contraception.
- The method of contraception specified in this study is the use of “condoms”.

(*Eligible seizure types: complex partial seizures, secondary generalized seizures, simple partial seizures with motor symptoms, primary generalized seizures, spasticity tonic-clonic seizures, atonic seizures

(1) If you have a severe intellectual disability
(2) If you have a history of major mental illness (e.g. mental illness or psychosis requiring hospitalization)
(3) If there is a history of substance abuse, eating disorder, or irritable bowel syndrome or disorder
(4) If you have had psychogenic non-epileptic seizures
(5) Patients with seizure clusters or other reasons that make the count of seizures inaccurate
(6) Women who are pregnant or breastfeeding
(7) In the case of disorders affecting the oxidation of medium-chain (KB1) and short-chain fatty acids
(8) Patients receiving a ketogenic diet or other calorie-controlled diets that may interfere with the implementation of the protocol of this clinical trial (if the patient agrees to discontinue the diet before and during the trial, it can be included as a subject. Baseline A withdrawal period of at least one month is required before the visit)

Seizure reduction rates in MCT oil intake group compared to sunflower oil intake group

All subjects Clinical trial end point

Drop-out rate in the MCT group, number of fatal adverse events in the MCT group

All subjects Clinical trial end point