Research on Cognitive Effect of Cannabidiol on Dravet Syndrome and Lennox-Gastaut SyndromeGastaut Syndrome

• ClinicalTrials.gov Identifier: NCT04611438
• Recruitment Status: Unknown
• First Posted: November 2, 2020
• Last Update Posted: November 2, 2020
• Sponsor: Yonsei University
• Information provided by (Responsible Party): Yonsei University

Tracking Information

• First Submitted Date: September 16, 2019
• First Posted Date: November 2, 2020
• Last Update Posted Date: November 2, 2020
• Actual Study Start Date: March 30, 2020
• Estimated Primary Completion Date: March 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 26, 2020)

• development assessment [ Time Frame: 24 weeks ]
  Assessment of cognition and development would be done by Bayley Scales of Infant Development, Wechsler Preschool and Primary Scale of Intelligence, Wechsler Intelligence Scale for Children, Developmental Test of Visual-Motor Integration, and CCTT according to the patient's age and capability.
• Seizure outcome [ Time Frame: 24 weeks ]
  Caregivers would report seizure outcome by Caregiver Global Impression of Change in Seizure Duration or Caregiver/patient Global Impression of Change. (CGIC)

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: October 26, 2020)

• Behavior assessment [ Time Frame: 24 weeks ]
  Behavior would be evaluated by Child Behavior Checklist (K-CBCL)
• Quality of life assessment [ Time Frame: 24 weeks ]
  Tool for evaluation quality of life is Quality of Life in Childhood Epilepsy questionnaire(K-QOLCE).

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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 Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Patients would be from 2 to 18 years old diagnosed with Dravet syndrome or Lennox-Gastaut syndrome, who are intractable to more than 2 antiepileptic medications. Caregivers would purchase cannabidiol and give it to the patient according to titration schedule. Patients would go through laboratory, neuropsychologic, and electroencephalographic tests before, during and after the intervention.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Dravet Syndrome
• Lennox Gastaut Syndrome

Intervention

Drug: Cannabidiol

Intervention schedule for each patient is as follows:

1. 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.

2. Treatment Period: Titration (2 weeks) + stabilization period (10 weeks) + maintenance period (12 weeks)

   • Titration: The patient would start cannabidiol on 5mg/kg/mg for 1 week and titrate dosage up to 10mg/kg/day for second week 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

Study Arms

Experimental: CBD

The patient would be on cannabidiol for 24 weeks and would go through laboratory, electroencephalography, and neuropsychological tests before, during, and after intervention.

Intervention: Drug: Cannabidiol

Publications *

• Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, Scheffer IE, Thiele EA, Wright S; Cannabidiol in Dravet Syndrome Study Group. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med. 2017 May 25;376(21):2011-2020. doi: 10.1056/NEJMoa1611618.
• Devinsky O, Patel AD, Cross JH, Villanueva V, Wirrell EC, Privitera M, Greenwood SM, Roberts C, Checketts D, VanLandingham KE, Zuberi SM; GWPCARE3 Study Group. Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome. N Engl J Med. 2018 May 17;378(20):1888-1897. doi: 10.1056/NEJMoa1714631.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: October 26, 2020): 107
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2021
• Estimated Primary Completion Date: March 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 18 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Korea, Republic of

Administrative Information

• NCT Number: NCT04611438
• Other Study ID Numbers: 4-2020-0120
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Yonsei University
• Original Responsible Party: Same as current
• Current Study Sponsor: Yonsei University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Yonsei University
• Verification Date: October 2020