Brief Title
Research on Cognitive Effect of Cannabidiol on Dravet Syndrome and Lennox-Gastaut SyndromeGastaut Syndrome
Official Title
A Prospective Multi-Center Single-Arm Clinical Trial on Cognitive Effect of Cannabidiol (CBD-OS®) on Dravet Syndrome and Lennox-Gastaut Syndrome
Brief Summary
The clinical trial "A Prospective Single-Center Single-Arm Clinical Trial on Cognitive Effect
of Cannabidiol (CBD-OS®) on Dravet syndrome and Lennox-Gastaut Syndrome" is a single-group
phase III study done in single tertiary referral center in Seoul, Korea.
Chief investigator is Dr. Hoon-Chul Kang of Severance Hospital, Yonsei University College of
Medicine. Associate investigators are Dr. Heung Dong Kim, Joon Soo Lee, Se Hee Kim, Han Som
Choi, Ji Hoon Na, Dong Hwa Yang, and Hee Jung Kang, of Severance Hospital, Yonsei University
College of Medicine.
The aim of the study is to evaluate the effect of cannabidiol (CBD-OS®) on cognitive
functions in patients aged from 2 to 18 years old diagnosed with Dravet syndrome or
Lennox-Gastaut syndrome. The duration of study is planned as one year, after patient
recruitment of 6 months. The intervention period in each patient is 24 weeks, with 2 weeks of
medication titration, stabilization period of 10 weeks, and maintenance period of 12 weeks.
The recruitment goal of patient number is 104, considering the study power of 90 percent.
Primary outcomes are improvement of cognitive and development and improvement of seizure
outcome. Secondary outcomes are improvement in behavior and quality of life.
Safety monitoring criteria are adverse event profiles and physician's and caregiver's global
assessment.
Statistical analysis of outcomes is subject only to the patients who completed the 24-week
medication and 2 times of tests before and after treatment of cannabidiol. Evaluation of
seizure outcomes would include all patients who completed the 24-week medication and those
who dropped out of the study, either by follow-up loss or discontinuation of medication due
to incomplete seizure control or adverse effect of the medication.
To evaluate safety, the investigators would measure adverse events and dropout rates by
percentage. The investigators would analyze overall evaluation of the caregivers and
investigator. Serious adverse events would be noted after causality evaluation.
Detailed Description
Selection criteria of the patients are as below:
1. Age: 2 years old to 18 years old
2. Investigation center: Severance hospital, Yonsei University College of Medicine, Seoul,
Korea
3. A) Diagnosed as Dravet syndrome by clinical manifestations and/or genetic test B)
Diagnosed as Lennox-Gastaut syndrome by clinical manifestations and
electroencephalography
4. The diagnosed patients by criteria 3-(1) or 3-(2) with intractable seizures after using
over two antiepileptic medications
5. Patients and caregivers who agreed to participation in this trial
Exclusion criteria of the patients are as below:
1. Patients with possibility of progressive central nervous system disease other systemic
disease
2. The patients who started additional antiepileptic medication during the investigation
period, with exception of short-term acute treatment of seizures (e.g. benzodiazepine
for rescue therapy)
3. Patients with alanine and aspartate aminotransferase and/or total bilirubin levels over
2 times of the normal range, or blood urea nitrogen and creatinine ratio over 3 times of
the normal range
4. Patient with hypersensitivity or allergic reactions to cannabidiol
5. patients who are incapable of executing cognitive tests, or cases whom the investigators
consider inappropriate to be enrolled in the trial Overall trial schedule for each
patient is as follows:
A) Baseline Phase (2 weeks)
- Baseline Phase starts from the screening visit, where the patient and caregiver write
permission to the trial and goes through laboratory, electroencephalography, and
neuropsychological tests.
B) Treatment Period : Titration(2 weeks) + stabilization period (10 weeks) + maintenance
period (12 weeks)
- Titration: cannabidiol titration up to 10mg/kg/day with the caregiver monitoring the
patient's tolerability
- Stabilization: caregiver monitoring the patient's tolerability, with no change in
medication dosage
- Maintenance: no change in medication dosage
- Statistical analysis of outcomes would be done as follows:
T-test would be done to compare each test before and after cannabidiol treatment. For
multiple results along the intervention time period, repeated data analyses would be done.
Continuous variables would be evaluated by repeated measures analysis of variance or
generalized estimating equations. Nominal variables would be evaluation by chi-squared test
or trend test.
Evaluation of seizure outcomes would include all patients who completed the 24-week
medication and those who dropped out of the study, either by follow-up loss or
discontinuation of medication due to incomplete seizure control or adverse effect of the
medication.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
development assessment
Secondary Outcome
Behavior assessment
Condition
Dravet Syndrome
Intervention
Cannabidiol
Study Arms / Comparison Groups
CBD
Description: The patient would be on cannabidiol for 24 weeks and would go through laboratory, electroencephalography, and neuropsychological tests before, during, and after intervention.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
107
Start Date
March 30, 2020
Completion Date
June 2021
Primary Completion Date
March 2021
Eligibility Criteria
Inclusion Criteria:
1. Age: 2 years old to 18 years old
2. Investigation center: Severance hospital, Yonsei University College of Medicine,
Seoul, Korea
3. (1) Diagnosed as Dravet syndrome by clinical manifestations and/or genetic test (2)
Diagnosed as Lennox-Gastaut syndrome by clinical manifestations and
electroencephalography
4. The diagnosed patients by criteria 3-(1) or 3-(2) with intractable seizures after
using over two antiepileptic medications
5. Patients and caregivers who agreed to participation in this trial
Exclusion Criteria:
1. Patients with possibility of progressive central nervous system disease other systemic
disease
2. The patients who started additional antiepileptic medication during the investigation
period, with exception of short-term acute treatment of seizures (e.g. benzodiazepine
for rescue therapy)
3. Patients with alanine and aspartate aminotransferase and/or total bilirubin levels
over 2 times of the normal range, or blood urea nitrogen and creatinine ratio over 3
times of the normal range
4. Patient with hypersensitivity or allergic reactions to cannabidiol
5. patients who are incapable of executing cognitive tests, or cases whom the
investigators consider inappropriate to be enrolled in the trial
Gender
All
Ages
2 Years - 18 Years
Accepts Healthy Volunteers
No
Contacts
, +82-2-2228-2050, [email protected]
Location Countries
Korea, Republic of
Location Countries
Korea, Republic of
Administrative Informations
NCT ID
NCT04611438
Organization ID
4-2020-0120
Responsible Party
Sponsor
Study Sponsor
Yonsei University
Study Sponsor
, ,
Verification Date
October 2020