Efficacy of Cannabidiol (CBD) in Patients with Treatment-Resistant Frontal Lobe Epilepsy

Evaluation of the effectiveness of cannabidiol on the seizure frequency, seizure severity, and quality of life in patients with drug-resistant frontal lobe epilepsy

Placebo-controlled, randomized, concealed, blinded, phase 3 clinical trial with a parallel group design of 15 patients in each group. A random number table has been used for randomization.

Patients with drug-resistant frontal lobe epilepsy were selected from previously evaluated patients at the epilepsy monitoring clinic of Imam Khomeini Hospital in Tehran and will be recruited to the study within four weeks. Measures such as clinical evaluations (number of seizures and severity of seizures) and quality of life questionnaire are performed and recorded before and after the intervention. A drug or placebo is given for 14 weeks. The administered dose will be 70 mg, 140 mg, and 210 mg in the first, second, and third to fourteenth weeks respectively. A telephone follow-up of patients will be considered once every two weeks.

Inclusion criterion is the diagnosis of focal refractory frontal lobe epilepsy (no response or inadequate response to treatment with two or more common antiepileptic drugs) and exclusion criteria are History of marijuana or cannabis use in recent month, pregnancy, and use of any of the drugs Clobazam, Des-methyl clobazam, Eslicarbazepine, Topiramate, Zonisamide, and Warfarin.

Patients are divided into two groups: intervention and placebo. Each of these groups received a specific dose as a solution containing 40 mg of drug or placebo per ml prepared by KMT company containing cannabidiol and placebo, respectively.

Decrease the seizure frequency following cannabidiol use

Randomization coincides with the allocation concealment by generating random codes - consisting of an English letter and two digits - generated using one of the web resources (here is random.org), printing the codes on a card, and placing the cards in a sealed envelope (SNOSE method). After generating the code list, fifteen codes will be assigned to the drug group, and the other fifteen codes are assigned to the placebo group (alternately assigned). This list will be delivered to the drug supplier, and each code is displayed properly as a label on the body of the drug box or placebo. Each code will be printed on one card that, after shuffling, are placed in opaque envelopes with aluminum inner lining numbered from 1 to 30, and the envelope lid will be completely sealed. The envelopes will be placed in a box and handed over to another researcher responsible for delivering the drugs to the participants. The patients who will be referred to assign to one of the two groups will be given an envelope. The envelope will be taken out of the box orderly, and the seal will be broken. According to the code in the envelope, the right drug box or placebo is delivered to the patient, and the patient's credentials are written on the envelope. Also, in a separate list, the person is assigned to the code taken out of the envelope. Thus, subsequent visits for re-delivery of the box containing a drug or placebo will be done precisely based on their code. In contrast, the researcher responsible for allocating patients and the participant themselves will not be aware of the type of intervention they will offer and receive. (Generating of the codes and assigning half of the codes to the intervention and the other half to the control will be done by another researcher who will not be responsible for these steps or any other steps)

Study participants will all be unaware of their group (drug or placebo) even though they know they will participate in a study that they will be given one of the two options: drug or placebo. Also, patients and personnel are completely blinded due to the exact similar label and specifications on boxes, color, taste, smell, and consistency between the drug and placebo. Clinical caregivers, researchers, and physicians responsible for diagnosis and treatment will be unaware of the type of treatment assigned to each participant. Those responsible for evaluating the results will also evaluate data and perform the statistical analysis by coding individuals without being aware of the patient group - drug or placebo. The Data Safety and Monitoring Committee is also unaware of people who have received the drug or placebo and only monitors the above-mentioned principles according to blinding، concealment, and data collection protocols.

The data of the study participants will be evaluated for statistical analysis, and their results will be published in the form of an article.

Immediately after the publication of the results in the form of a scientific article, the results of data analysis will be available to researchers at the request of the data.

Researchers of this project and individuals who have the right to access the project data based on the written permission of the corresponding researcher can access the project data.

If the permission of the main researcher of the project is obtained with an acceptable justification and explanation, the data obtained from this project can be used.

Imam Khomeini Hospital Complex, Neurological Diseases Research Center, Second Floor, Epilepsy Monitoring Unit, Research Unit

A written request will be sent to the researcher in charge of the study (Dr. Abbas Tafakhori) with appropriate evidence and justification; Once approved by him, access to data and documents will be possible.