A Double-Blind Trial to Evaluate Efficacy and Safety of Cannabidiol as an add-on Therapy for Treatment in Refractory Epilepsy

This is an interventional treatment trial for Epilepsy Read More

Inclusion Criteria:

• Men and women aged 2 years to 18 years.
• Diagnosis of treatment-resistant epilepsy according to the criteria of the International League Against Epilepsy (ILAE) (Kwan et al., 2010).
• Participants with at least 4 epileptic seizures with intervals no longer than 21 days.
• In treatment with up to 3 AEDs concomitantly and at stable doses for at least 1 month before the baseline assessment and expected to remain stable during the period of the trial. Vagus nerve stimulation (VNS) will be considered as an AED.
• Availability of a legal guardian able to follow the protocol (e.g., understand and fill up diaries) and visitation and medication schemes, according to the decision of the investigator.
• Availability of brain neuroimaging exams (magnetic resonance or computed tomography) collected within the last 5 years.
• No significant comorbid conditions, according to medical decision, to other criteria in this Protocol, and to additional assessments: medical records, blood pressure, heart rate, and temperature measures, physical exam, ECG, EEG, and laboratory tests.
• Women in reproductive age may be included as long as they are sexually abstinent or using effective contraceptive methods.
• Participants and their legal guardians, when applicable, must sign an informed consent form approved by the local ethics committee.

Exclusion Criteria:

• Occurrence of simple partial seizures (preserved consciousness) only, with no motor symptomatology.
• History or presence of pseudoseizures.
• History of suicide attempt.
• History of major depression.
• Pregnancy.
• Drug use.
• Hypertension.
• Participants with severe dysphagia and no gastric or nasogastric tubes.
• Current treatment with drugs that may significantly affect the metabolism of CBD, except AEDs if stable for at least 1 month before the screening interview.
• Presence of any clinical or neuroimaging finding suggestive of brain disorders, brain tumors, or metabolic or neurodegenerative diseases of rapid progression.
• Presence of acute and clinically significant diseases as assessed by a medical investigator, such as kidney, liver, urinary, bowel, or respiratory infections.
• Presence of known chronic and clinically significant diseases as assessed by a medical investigator and which may interfere with participation in the trial or pose safety risks for the participant.
• History of liver, kidney, lung, hematological, heart, or psychiatric diseases that may affect the volunteers' health or participation in the trial.
• Hypotension or hypertension with any etiology and requiring pharmacological management.
• History of surgeries that may affect the volunteers' health and/or participation in the trial.
• Regular or intermittent use of marijuana over the 60 days preceding the baseline assessment.
• Regular or intermittent treatment with CBD over the 60 days preceding the baseline assessment.
• History of allergies or idiosyncratic reactions to Cannabis sativa derivatives or components of the pharmaceutical formulation.
• Clinically significant ECG alterations as judged by a medical investigator.
• Participation in other clinical trials within less than 3 months before the baseline assessment.
• Donation or loss of 450 mL or more of blood within 90 days before the baseline assessment.
• Impaired liver function: AST, ALP, alkaline phosphatase and γGT values more than 3 times above the upper limit of the reference value. Results of γGT values 3 times above the upper limit will only be accepted if attributable to liver enzymatic induction caused by concomitant treatment with AEDs and with levels of other liver enzymes lower than 3 times the upper limit of the reference range.
• Participants with clinically significant discrepancies from the reference ranges of the following laboratory tests: creatinine clearance < 50 ml/min, platelets < 100.000/μL, and neutrophils < 1.800/μL.