Epilepsy
Conditions
Brief 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).
Interventions
DRUGCannabidiol
Oral solution of cannabidiol 200 mg / mL dissolved in corn oil. Titration period: 5 mg / kg / day up to 25 mg / kg / day. Maintenance period: highest dose obtained during the titration period (maximum of 25 mg/kg / day)
DRUGPlacebo
The placebo will be an oral solution of corn oil. Titration period: 5 mg / kg / day up to 25 mg / kg / day. Maintenance period: highest dose obtained during the titration period (maximum of 25 mg/kg / day)
Sponsors
Prati Donaduzzi & Cia Ltda
Antonio Waldo Zuardi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 18 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Frequency of epileptic seizures | 17 th week |
Countries
Brazil
Outcome results
None listed