Investigation of effectiveness of sake yeast supplementation (Saccharomyces cerevisiae) and S-sdenosyl methionine (SAM) in pharmacoresistant epileptic patients

Evaluation of the effects of sake supplement and its active ingredient (S-adenosyl methionine) on seizures (and depression/memory function) in patients with drug-resistant epilepsy

This study will be a phase 3 randomized, double-blind, placebo-controlled clinical trial with cross-sectional pattern. Study groups will include treatment group 1 (receiving sake supplement) containing 30 samples, treatment group 2 (receiving S-adenosyl methionine) containing 30 samples and eventually control group (receiving placebo) containing 30 samples. Randomization is simple, individual and by random numbers intervention and control groups

The study will be performed and conducted on 120 patients at Kosar Hospital and Imam Hossein Hospital in Semna and Tehran, respectively. Two groups of 30 patients will receive 500 mg sake (or 3200-1600 mg S-adenosyl methionine) tablets daily for 12 consecutive weeks and after 2 weeks of washout, they will receive placebo tablets daily for 12 consecutive weeks. In contrast, the other two groups of 30 people will receive placebo tablets daily for 12 consecutive weeks, and after 2 weeks of washout, they will receive the two drugs (one drug in each of the 30 groups of patients) daily for 12 consecutive weeks.

Inclusion criteria: Pharmacoresistant epileptic patients who have not responded to any of the anticonvulsant drugs on the market for at least one year. Exclusion criteria: Cancelations, uncontrolled blood pressure, malignancy, history of alcoholism or drug abuse, pregnancy, and lactation.

Treatment group 1: Receiving sake yeast Treatment group 2: Receiving S-adenosyl methionine Control group: Receiving placebo

Seizure severity will be assessed based on the frequency of daily seizures (specified in the questionnaires)

Permuted block randomization will be performed. Blocking is usually used to balance the number of samples assigned to each of the groups studied. A common method is to ensure that during the process of random division, number of people between groups have been distributed equally. 4 blocks will be used. This means that in a study with 60 members, exactly 30 people are assigned to each group (treatment and control). We have two treatment (T) and placebo or control (C) groups. There are six different modes for 4 blocks: 1. TCCT 2. TCTC 3. TTCC 4. CTTC 5. CTCT 6. CCTT • We create random numbers by a computer. For numbers between 0 and 1/6 compound 1 (TCCT), numbers between 2.6 to 1.6 compound 2 (TCTC) and so on.

Medications will be coded by a third person (outside the study) (e.g., the main treatment group number 1 and placebo group number 2). Then the stickers of the medications are removed and the drugs will be available to the student (responsible for the correct follow-up and administration of the medications). Student sees only the number and does not know the type of medicine. The patient merely knows that he/she will be given a medication that will help his/her problem and is completely unaware of the type of medication. After administering the drugs and registering the data by the student, the data will be provided to the statistical analyst (which he/she knows only the number but not the type of medication). After statistical analysis, the data will be available to the researcher responsible for writing the article. To write the article, the main researcher will also use the third person (outside the study) to match the numbers to the type of medication