a double-blind trial to evaluate efficacy and safety of cannabidiol as an add-on therapy for treatment in refractory epilepsy

Conditions: Epilepsy

Summary: the purpose of this study is to assess the efficacy of the adjuvant use of cannabidiol administered twice daily in doses of 5-25 mg/kg/day through the proportion of responsive patients; that is, participants with at least 50% decrease in the frequency of epileptic seizures in the last month of the trial relative to baseline (pretreatment with aeds only). primary end point(s): rate of responsive patients; that is, participants with at least 50% decrease in the frequency of epileptic seizures in the last month of the trial relative to baseline (pretreatment with aeds only).


Eligibility criteria:
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.