CClinicalTrials.gg
CompletedNCT04447846Updated May 25, 2023Results posted

Novel Cognitive Treatment Targets for Epidiolex in Sturge- Weber Syndrome

A Phase 2 interventional study of Cannabidiol in Sturge-Weber Syndrome, sponsored by Anne Comi, MD. Completed at 1 site in United States. Open to participants aged 3 Years to 50 Years. Per ClinicalTrials.gov, last updated 2023-05-25.

Sponsored by Anne Comi, MD · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
11
Allocation
Not applicable
Ages
3 Years to 50 Years
Sex
All
01

Study summary

The purpose of this study is to better understand the utility of cannabidiol (CBD/ Epidiolex) for improving the treatment of cognitive impairments in Sturge-Weber syndrome (SWS).

Read the detailed description

The investigators hope to gain an understanding of the utility of pharmaceutical grade CBD used for the treatment of cognitive impairments in SWS in this open-label study. Anecdotal evidence from a phase I trial investigating the use of CBD for medically refractory seizures suggests CBD may also have a beneficial effect on cognition, mood, and behavior. The investigators hypothesize that CBD/ Epidiolex will improve SWS brain function resulting in improved cognitive function, social interactions, mood, motor function and behavior, as well as reduced migraines. This is an open-label prospective oral drug trial of Epidiolex in 10 subjects. Assessments will be done at baseline and repeated after 6 months on study drug.

02

Conditions studied

  • Sturge-Weber Syndrome

Keywords

  • Sturge-Weber Syndrome
  • SWS
  • Cognitive impairments
03

Who can participate

Ages eligible
3 Years to 50 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Inclusion Criteria: Participants with Sturge-Weber syndrome brain involvement as defined on neuroimaging (n=10 subjects, male and female, ages 3 to 50 years of age) and the following:

  • Cognitive impairment defined as a cognitive neuroscore greater than or equal to 2 at screening.
  • Anti-epileptic, mood or behavioral drugs (if on) at stable doses for a minimum of 4 weeks prior to enrollment.
  • If present, VNS must be on stable setting for a minimum of 3 months prior to enrollment.
  • If on ketogenic or Atkins diet, must be on stable ratio for a minimum of 3 months prior to enrollment.
  • Previous subjects who fail at any point to meet continuation criteria and withdraw early may be considered for re-enrollment under new subject ID as long as the above inclusion criteria are met. The determination of whether to re-enroll will be made by the PI and sponsor on a case-by-case basis. Re-enrollment can occur no earlier than 4 weeks after the final, post-weaning follow-up visit under the old subject ID.
  • Written informed consent obtained from the patient or the patient's legal representative must be obtained prior to beginning treatment.

Exclusion Criteria:

  • Patients with any severe and/or uncontrolled medical conditions at randomization such as:

    1. Liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable HBV-DNA and/or positive HbsAg, quantifiable HCV-RNA)
    2. Uncontrolled diabetes as defined by fasting serum glucose greater than 1.5
    3. Active (acute or chronic) or uncontrolled severe infections
    4. Active, bleeding diathesis
  • Patients who have a major surgery or significant traumatic injury within 4 weeks of study entry, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia), or patients that may require major surgery during the course of the study.
  • Patients who start or discontinue a seizure, mood or behavioral medication in the 4 weeks leading up to screening.
  • Prior treatment with any investigational drug or use of any other cannabis product within the preceding 4 weeks prior to study entry.
  • Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study. This includes those in foster care, or those unable to keep follow-up appointments, maintain close contact with the Principal Investigator, or complete all necessary studies to maintain safety.
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of the female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
11 participants (actual)

Study arms

  • Experimental
    Cannabidiol/ Epidiolex

    All subjects will receive the experimental Epidiolex (cannabidiol) oral solution to be taken at home twice a day, and will be treated on an outpatient basis. The drug will be taken for 24 weeks unless the subject chooses to participate in the extension phase of the study, in which case the subject will continue to receive the drug for one additional year or until the drug is approved for clinical use for the treatment of cognitive impairments in patients with Sturge-Weber syndrome.

    Drug: Cannabidiol

Interventions

  • DrugCannabidiol

    Initiation of treatment will begin with 5 mg/kg/day given in two divided doses. The dose will be increased by 5 mg/kg/day after seven days and then by 5 mg/kg/day every seven days up to a maximum dose of 20 mg/kg/day given.

    Also known as: Epidiolex, CBD

05

What researchers measure

Primary outcomes

  1. List Sorting Working Memory Test

    Data on cognitive function was collected using the List Sorting Working Memory Test from the NIH Toolbox. Data was collected on working memory performance, which was transformed into a t-score from 0 to 100 where a higher t-score indicates better performance. T-score of 50 indicates the population mean with a standard deviation of 10. Data was collected at baseline and after 6 months on study drug.

    Time frame: Baseline, Follow-up (6 months)

Secondary outcomes

  1. Picture Vocabulary Test

    Data on cognitive function was collected using the Picture Vocabulary subtest from the NIH Toolbox. Single words are presented via an audio file, paired simultaneously with 4 screen images of objects, actions, and/or depictions of concepts. The task is to pick the picture that matches the spoken word. Performance on the task was transformed into a t-score from 0 to 100 where a higher t-score indicates better performance. T-score of 50 indicates the population mean with a standard deviation of 10. Data was collected at baseline and after 6 months on study drug.

    Time frame: Baseline, Follow-up (6 months)

  2. Seizure Frequency

    Change in seizure frequency by seizure score at pre-treatment baseline and after six months. The seizure score is taken from the Sturge-Weber Neuroscore on a scale of 0 to 4 where 0=none, 1=1+. but controlled, 2=Breakthrough, 3=monthly, 4=Weekly+. Higher scores indicate worse outcome.

    Time frame: Baseline, Follow-up (6 months)

  3. Migraine Severity

    Data on migraine severity will be collected using patient responses to questions on a standard six-point scale. Data will be collected on the frequency of an event (e.g. feelings of frustration, performance of daily activities) which will be transformed into a score from 0 to 100 where higher scores indicate a less migraine severity and better outcomes. Data will be collected at baseline and after 6 months on study drug.

    Time frame: Baseline, Follow-up (6 months)

  4. Modified House Classification Scores

    Data on motor function was collected using a Modified House Classification. Data was collected on the ability to complete a task with the subject's non-dominant hand which was transformed into a score from 1 to 8 and 0 to 32 where higher scores indicate better motor function. Data was collected at baseline and after 6 months on study drug.

    Time frame: Baseline, Follow-up (6 months)

  5. Erhardt Developmental Prehension Assessment Scores

    Data on motor function was collected using the Erhardt Developmental Prehension assessment. Data was collected on the ability to complete a task with each hand, which was scored as age equivalence of task performance (in months). Higher scores indicate better motor function. Data was collected at baseline and after 6 months on study drug.

    Time frame: Baseline, Follow-up (6 months)

  6. Pediatric Evaluation of Disability Inventory Computer Adapted Test

    Data on motor function was collected using the Pediatric Evaluation of Disability Inventory Computer Adapted Test. Data was collected on the subject's ability to complete tasks involved in daily activities, mobility, and social/ cognitive activities. The data was transformed into scaled scores ranging from 20 to 80, where higher scores indicate better motor function. Data was collected at baseline and after 6 months on study drug.

    Time frame: Baseline, Follow-up (6 months)

  7. ABILHAND Questionnaire

    Data on motor function was collected using the ABILHAND questionnaire, a measure of manual ability for adults with upper limb impairments. Data was collected on the subject's ability to complete daily activities that involve the upper limbs. Score was collected as a patient measure with scores ranging from -10 to 10. Higher scores indicate better motor function. Data was collected at baseline and after 6 months on study drug.

    Time frame: Baseline, Follow-up (6 months)

  8. Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V) or Wechsler Adult Intelligence Scale (WAIS-IV)

    Data on cognitive function was collected using selected subtests, from either the Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V) or the Wechsler Adult Intelligence Scale (WAIS-IV). For the WISC-V and WAIS-IV subtests selected, scaled scores were derived from the normative data which account for age and demographic information. The selected WISC-V/WAIS-IV subtests were as follows: Digit Span, Symbol Search, Coding and Processing Speed; the first three subtests were scored from 0-10, the fourth subtest from 0-100, and for all subtests higher score is better. The selected subtests, from the WISC-V and the WAIS-IV, were combined to increase statistical power. Statistically rare changes in individual test scores were determined using a reliable change index methodology based upon normative information for these assessments.

    Time frame: Baseline, Follow-up (6 months)

  9. Pediatric Neurological Quality of Life (Neuro-QoL)

    Data on cognitive function was collected using Neurological Quality of Life scales from the NIH Toolbox. Data on frequency of an event (e.g. forgetting schoolwork) was collected and transformed into a t-score from 0 to 100 where higher t-scores indicate worse anger, worse anxiety, worse pain, better social relationships, worse stigma, worse depression, better cognitive function, and worse fatigue. T-score of 50 indicates the population mean with a standard deviation of 10. Data was collected at baseline and 6 months on study drug.

    Time frame: Baseline, Follow-up (6 months)

  10. Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2)

    Data on executive function was collected using the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2). Data on the frequency of an event (e.g. becomes upset too easily) was collected and transformed into a t-score. The following BRIEF-2 subtests were evaluated: Behavioral Regulation Index, Emotional Regulation Index, Cognitive Regulation Index, and Global Executive Composite. For each BRIEF-2 subtest, t-scores range from 0 to 100; a score of 50 indicates the population mean with a standard deviation of 10. For all BASC-3 subtests, higher scores are worse outcome.

    Time frame: Baseline, Follow-up (6 months)

  11. Social Responsiveness Scale, Second Edition (SRS-2)

    Data on social function was collected using the Social Responsiveness Scale-Second Edition (SRS-2). Data on a child's ability to engage in emotionally appropriate reciprocal social interactions in naturalistic settings was collected and transformed into a t-score from 0 to 100 where higher scores indicate greater impairment in social function. T-score of 50 indicates the population mean with a standard deviation of 10. Data was collected at baseline and 6 months on study drug.

    Time frame: Baseline, Follow-up (6 months)

  12. Behavioral Assessment System for Children, Third Edition (BASC-3)

    Data on behavioral function was collected using the Behavioral Assessment System for Children, Third Edition (BASC-3). Data on the frequency of a behavior (e.g. avoids eye contact) was collected and transformed into a t-score. Subscales for the BASC-3 scored were: External Problems Composite, the Internal Problems Composite, the Behavioral Symptoms Index, and the Adaptive Skills Composite. For the first three subscales, lower t-score indicates better outcome; for the fourth, a lower t-score indicates worse outcome. T-scores for all the BASC-3 subscales range from 0 to 100, and a t-score of 50 indicates the population mean with a standard deviation of 10.

    Time frame: Baseline, Follow-up (6 months)

  13. Screen for Child Anxiety Related Disorders (SCARED)

    Data on anxiety was collected using the Screen for Child Anxiety Related Disorders (SCARED). Data on the truthfulness of a statement (e.g. I am nervous) was collected and transformed into a score from 0 to 82 where higher scores indicate greater anxiety. Data was collected at baseline and 6 months on study drug.

    Time frame: Baseline, Follow-up (6 months)

  14. Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55)

    Data on quality of life was collected using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55). Data on the frequency of an event (e.g. had trouble concentrating on a task) was collected and transformed into a score from 0 to 100 where higher scores reflect better quality of life. Data was collected at baseline and 6 months on study drug.

    Time frame: Baseline, Follow-up (6 months)

  15. Safety of Epidiolex

    Safety of Epidiolex was measured by the number of adverse events and serious adverse events that result from study drug.

    Time frame: Baseline, Follow-up (6 months)

  16. Neuroscore

    Data on neurological function was collected using the Neuroscore. Data on frequency of seizures, extent of hemiparesis, assessment of visual field cut, and degree of cognitive functioning was transformed into a score from 0 to 15 where higher scores indicate worse neurologic function. Data was collected at baseline and 6 months on study drug.

    Time frame: Baseline, Follow-up (6 months)

  17. Port-wine Birthmark Score

    Data on facial port-wine birthmarks was collected using the Port-wine Birthmark Score. Data on percent of face covered, thickness of birthmark, and darkness of birthmark color was collected and transformed into a score from 0 to 43 where higher scores indicate greater severity and greater surface area involved. Data was collected at baseline and 6 months on study drug.

    Time frame: Baseline, Follow-up (6 months)

  18. Adult Neurological Quality of Life (Neuro-QoL)

    Data on cognitive function was collected using Neurological Quality of Life scales from the NIH Toolbox. Data on frequency of an event was collected and transformed into a t-score from 0 to 100. Higher t-scores indicate better communication, better ability to participate in social activity, worse anxiety, worse depression, worse emotional and behavioral dyscontrol, worse fatigue, better positive affect, worse sleep disturbance, better lower and upper extremity functions, worse stigma, better satisfaction with social roles, and better cognitive function. T-score of 50 indicates the population mean with a standard deviation of 10. Data was collected at baseline and 6 months on study drug.

    Time frame: Baseline, Follow-up (6 months)

06

Results

Posted May 25, 2023
Limitations and caveats
Due to the COVID-19 , visits transitioned from an in-person setting to a remote setting. Four subjects had baseline testing conducted in person and follow-up virtually, and 5 subjects had both baseline and follow-up testing virtually. The differences in testing environment and the context of the pandemic may have affected results. Also, due to variability in subject age and the small number of subjects, some participants were outside of assessment age norms.

Participant flow

Participant flow — Overall Study
MilestoneCannabidiol/ Epidiolex
Started10
Completed9
Not completed1
Withdrew: Withdrew due to moderate side effects (fatigue)1

Outcome measures

PrimaryList Sorting Working Memory Test

Data on cognitive function was collected using the List Sorting Working Memory Test from the NIH Toolbox. Data was collected on working memory performance, which was transformed into a t-score from 0 to 100 where a higher t-score indicates better performance. T-score of 50 indicates the population mean with a standard deviation of 10. Data was collected at baseline and after 6 months on study drug.

Time frame:
Baseline, Follow-up (6 months)
Reported as:
Mean · T-score
List Sorting Working Memory Test
T-scoreCannabidiol/ Epidiolex
Baseline List Sorting Working Memory Fully Adjusted Score37.14 ± 10.92
Follow-Up List Sorting Working Memory Fully Adjusted Score39.14 ± 13.78
SecondaryPicture Vocabulary Test

Data on cognitive function was collected using the Picture Vocabulary subtest from the NIH Toolbox. Single words are presented via an audio file, paired simultaneously with 4 screen images of objects, actions, and/or depictions of concepts. The task is to pick the picture that matches the spoken word. Performance on the task was transformed into a t-score from 0 to 100 where a higher t-score indicates better performance. T-score of 50 indicates the population mean with a standard deviation of 10. Data was collected at baseline and after 6 months on study drug.

Time frame:
Baseline, Follow-up (6 months)
Reported as:
Mean · T-score
Picture Vocabulary Test
T-scoreCannabidiol/ Epidiolex
Baseline Mean of the Fully Adjusted Picture Vocabulary Score42.88 ± 8.86
Follow-up Mean of the Fully Adjusted Picture Vocabulary Score42.38 ± 9.43
SecondarySeizure Frequency

Change in seizure frequency by seizure score at pre-treatment baseline and after six months. The seizure score is taken from the Sturge-Weber Neuroscore on a scale of 0 to 4 where 0=none, 1=1+. but controlled, 2=Breakthrough, 3=monthly, 4=Weekly+. Higher scores indicate worse outcome.

Time frame:
Baseline, Follow-up (6 months)
Reported as:
Mean · score on a scale
Seizure Frequency
score on a scaleCannabidiol/ Epidiolex
Baseline Seizure Score from Sturge-Weber Neuroscore1.11 ± 0.33
Follow-up Seizure Score from Sturge-Weber Neuroscore1.00 ± 0.00
SecondaryMigraine Severity

Data on migraine severity will be collected using patient responses to questions on a standard six-point scale. Data will be collected on the frequency of an event (e.g. feelings of frustration, performance of daily activities) which will be transformed into a score from 0 to 100 where higher scores indicate a less migraine severity and better outcomes. Data will be collected at baseline and after 6 months on study drug.

Time frame:
Baseline, Follow-up (6 months)
Reported as:
Mean · score on a scale
Migraine Severity
score on a scaleCannabidiol/ Epidiolex
Baseline Mean Migraine-Quality of Life Score96.83 ± 7.62
Follow-up Mean Migraine-Quality of Life Score97.50 ± 4.69
SecondaryModified House Classification Scores

Data on motor function was collected using a Modified House Classification. Data was collected on the ability to complete a task with the subject's non-dominant hand which was transformed into a score from 1 to 8 and 0 to 32 where higher scores indicate better motor function. Data was collected at baseline and after 6 months on study drug.

Time frame:
Baseline, Follow-up (6 months)
Reported as:
Mean · score on a scale
Modified House Classification Scores
score on a scaleCannabidiol/ Epidiolex
Baseline Mean Highest Category in Which All Items were Successfully Completed5.11 ± 0.93
Follow-up Mean Highest Category in Which All Items were Successfully Completed5.44 ± 1.33
Baseline Mean Total Number of Items Successfully Completed26.67 ± 4.12
Follow-up Mean Total Number of Items Successfully Completed27.44 ± 4.75
SecondaryErhardt Developmental Prehension Assessment Scores

Data on motor function was collected using the Erhardt Developmental Prehension assessment. Data was collected on the ability to complete a task with each hand, which was scored as age equivalence of task performance (in months). Higher scores indicate better motor function. Data was collected at baseline and after 6 months on study drug.

Time frame:
Baseline, Follow-up (6 months)
Reported as:
Mean · Months
Erhardt Developmental Prehension Assessment Scores
MonthsCannabidiol/ Epidiolex
Baseline Mean Dominant Hand Total Score54.22 ± 2.64
Follow-up Mean Dominant Hand Total Score53.56 ± 4.04
Baseline Mean Non-Dominant Hand Total Score51.22 ± 9.48
Follow-up Mean Non-Dominant Hand Total Score53.78 ± 4.15
SecondaryPediatric Evaluation of Disability Inventory Computer Adapted Test

Data on motor function was collected using the Pediatric Evaluation of Disability Inventory Computer Adapted Test. Data was collected on the subject's ability to complete tasks involved in daily activities, mobility, and social/ cognitive activities. The data was transformed into scaled scores ranging from 20 to 80, where higher scores indicate better motor function. Data was collected at baseline and after 6 months on study drug.

Time frame:
Baseline, Follow-up (6 months)
Reported as:
Mean · score on a scale
Pediatric Evaluation of Disability Inventory Computer Adapted Test
score on a scaleCannabidiol/ Epidiolex
Baseline Mean Score for Daily Activities58.67 ± 7.76
Follow-up Mean Score for Daily Activities60.00 ± 6.50
Baseline Mean Score for Mobility67.11 ± 4.76
Follow-Up Mean Score for Mobility68.56 ± 4.07
Baseline Mean Score for Responsibility52.44 ± 11.67
Follow-Up Mean Score for Responsibility53.89 ± 11.10
Baseline Mean Score for Social Cognitive66.89 ± 5.35
Follow-up Mean Score for Social Cognitive67.22 ± 4.63
SecondaryABILHAND Questionnaire

Data on motor function was collected using the ABILHAND questionnaire, a measure of manual ability for adults with upper limb impairments. Data was collected on the subject's ability to complete daily activities that involve the upper limbs. Score was collected as a patient measure with scores ranging from -10 to 10. Higher scores indicate better motor function. Data was collected at baseline and after 6 months on study drug.

Time frame:
Baseline, Follow-up (6 months)
Reported as:
Mean · score on a scale
ABILHAND Questionnaire
score on a scaleCannabidiol/ Epidiolex
Baseline Mean of the ABILHAND1.81 ± 1.98
Follow-up Mean of the ABILHAND2.88 ± 1.39
SecondaryWechsler Intelligence Scale for Children, Fifth Edition (WISC-V) or Wechsler Adult Intelligence Scale (WAIS-IV)

Data on cognitive function was collected using selected subtests, from either the Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V) or the Wechsler Adult Intelligence Scale (WAIS-IV). For the WISC-V and WAIS-IV subtests selected, scaled scores were derived from the normative data which account for age and demographic information. The selected WISC-V/WAIS-IV subtests were as follows: Digit Span, Symbol Search, Coding and Processing Speed; the first three subtests were scored from 0-10, the fourth subtest from 0-100, and for all subtests higher score is better. The selected subtests, from the WISC-V and the WAIS-IV, were combined to increase statistical power. Statistically rare changes in individual test scores were determined using a reliable change index methodology based upon normative information for these assessments.

Time frame:
Baseline, Follow-up (6 months)
Reported as:
Mean · score on a scale
Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V) or Wechsler Adult Intelligence Scale (WAIS-IV)
score on a scaleCannabidiol/ Epidiolex
Baseline Mean Digit Span Score5.71 ± 2.81
Follow-up Mean Digit Span Score6.43 ± 2.07
Baseline Mean Symbol Search Score6.00 ± 2.71
Follow-up Mean Symbol Search Score5.57 ± 2.07
Baseline Mean Coding Score5.57 ± 2.88
Follow-up Mean Coding Score4.71 ± 2.22
Baseline Mean Processing Speed Score77.14 ± 13.93
Follow-up Mean Processing Speed Score73.43 ± 11.19
SecondaryPediatric Neurological Quality of Life (Neuro-QoL)

Data on cognitive function was collected using Neurological Quality of Life scales from the NIH Toolbox. Data on frequency of an event (e.g. forgetting schoolwork) was collected and transformed into a t-score from 0 to 100 where higher t-scores indicate worse anger, worse anxiety, worse pain, better social relationships, worse stigma, worse depression, better cognitive function, and worse fatigue. T-score of 50 indicates the population mean with a standard deviation of 10. Data was collected at baseline and 6 months on study drug.

Time frame:
Baseline, Follow-up (6 months)
Reported as:
Mean · T-score
Pediatric Neurological Quality of Life (Neuro-QoL)
T-scoreCannabidiol/ Epidiolex
Baseline Mean Pediatric Score for Anger53.02 ± 3.09
Follow-up Mean Pediatric Score for Anger49.67 ± 7.00
Baseline Mean Pediatric Score for Anxiety45.20 ± 5.79
Follow-up Mean Pediatric Score for Anxiety41.07 ± 5.74
Baseline Mean Pediatric Score for Pain40.20 ± 4.16
Follow-up Mean Pediatric Score for Pain43.50 ± 5.89
Baseline Mean Pediatric Score for Social Relations43.28 ± 15.10
Follow-up Mean Pediatric Score for Social Relations54.33 ± 6.96
Baseline Mean Pediatric Score for Stigma42.45 ± 6.42
Follow-up Mean Pediatric Score for Stigma44.52 ± 4.88
Baseline Mean Pediatric Score for Depression44.07 ± 6.29
Follow-up Mean Pediatric Score for Depression44.62 ± 8.58
Baseline Mean Pediatric Score for Cognitive Function49.27 ± 3.36
Follow-up Mean Pediatric Score for Cognitive Function51.33 ± 6.44
Baseline Mean Pediatric Score for Fatigue46.38 ± 9.44
Follow-up Mean Pediatric Score for Fatigue45.97 ± 8.14
SecondaryBehavior Rating Inventory of Executive Function, Second Edition (BRIEF-2)

Data on executive function was collected using the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2). Data on the frequency of an event (e.g. becomes upset too easily) was collected and transformed into a t-score. The following BRIEF-2 subtests were evaluated: Behavioral Regulation Index, Emotional Regulation Index, Cognitive Regulation Index, and Global Executive Composite. For each BRIEF-2 subtest, t-scores range from 0 to 100; a score of 50 indicates the population mean with a standard deviation of 10. For all BASC-3 subtests, higher scores are worse outcome.

Time frame:
Baseline, Follow-up (6 months)
Reported as:
Mean · T-score
Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2)
T-scoreCannabidiol/ Epidiolex
Baseline Mean for Behavioral Regulation Index55.11 ± 11.66
Follow-Up Mean for Behavioral Regulation Index52.44 ± 13.60
Baseline Mean for Emotional Regulation Index60.22 ± 10.24
Follow-up Mean for Emotional Regulation Index51.22 ± 12.29
Baseline Mean for Cognitive Regulation Index54.11 ± 7.06
Follow-up Mean for Cognitive Regulation Index54.22 ± 10.59
Baseline Mean for Global Executive Composite56.78 ± 8.17
Follow-up Mean for Global Executive Composite53.33 ± 11.57
SecondarySocial Responsiveness Scale, Second Edition (SRS-2)

Data on social function was collected using the Social Responsiveness Scale-Second Edition (SRS-2). Data on a child's ability to engage in emotionally appropriate reciprocal social interactions in naturalistic settings was collected and transformed into a t-score from 0 to 100 where higher scores indicate greater impairment in social function. T-score of 50 indicates the population mean with a standard deviation of 10. Data was collected at baseline and 6 months on study drug.

Time frame:
Baseline, Follow-up (6 months)
Reported as:
Mean · T-score
Social Responsiveness Scale, Second Edition (SRS-2)
T-scoreCannabidiol/ Epidiolex
Baseline Mean Total Score54.22 ± 7.71
Follow-up Mean Total Score49.22 ± 7.09
SecondaryBehavioral Assessment System for Children, Third Edition (BASC-3)

Data on behavioral function was collected using the Behavioral Assessment System for Children, Third Edition (BASC-3). Data on the frequency of a behavior (e.g. avoids eye contact) was collected and transformed into a t-score. Subscales for the BASC-3 scored were: External Problems Composite, the Internal Problems Composite, the Behavioral Symptoms Index, and the Adaptive Skills Composite. For the first three subscales, lower t-score indicates better outcome; for the fourth, a lower t-score indicates worse outcome. T-scores for all the BASC-3 subscales range from 0 to 100, and a t-score of 50 indicates the population mean with a standard deviation of 10.

Time frame:
Baseline, Follow-up (6 months)
Reported as:
Mean · T-score
Behavioral Assessment System for Children, Third Edition (BASC-3)
T-scoreCannabidiol/ Epidiolex
Baseline Mean External Problems Composite51.22 ± 6.10
Follow-up Mean External Problems Composite50.11 ± 6.31
Baseline Mean Internal Problems Composite52.22 ± 5.81
Follow-Up Mean Internal Problems Composite46.22 ± 7.17
Baseline Mean Behavioral Symptoms Index54.22 ± 4.21
Follow-up Mean Behavioral Symptoms Index50.11 ± 8.19
Baseline Mean Adaptive Skills Composite45.00 ± 8.29
Follow-Up Mean Adaptive Skills Composite48.44 ± 7.63
SecondaryScreen for Child Anxiety Related Disorders (SCARED)

Data on anxiety was collected using the Screen for Child Anxiety Related Disorders (SCARED). Data on the truthfulness of a statement (e.g. I am nervous) was collected and transformed into a score from 0 to 82 where higher scores indicate greater anxiety. Data was collected at baseline and 6 months on study drug.

Time frame:
Baseline, Follow-up (6 months)
Reported as:
Mean · score on a scale
Screen for Child Anxiety Related Disorders (SCARED)
score on a scaleCannabidiol/ Epidiolex
Baseline Mean of Total Score14.86 ± 14.49
Follow-up Mean of Total Score11.57 ± 11.16
SecondaryQuality of Life in Childhood Epilepsy Questionnaire (QOLCE-55)

Data on quality of life was collected using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55). Data on the frequency of an event (e.g. had trouble concentrating on a task) was collected and transformed into a score from 0 to 100 where higher scores reflect better quality of life. Data was collected at baseline and 6 months on study drug.

Time frame:
Baseline, Follow-up (6 months)
Reported as:
Mean · score on a scale
Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55)
score on a scaleCannabidiol/ Epidiolex
Baseline Mean Total Score61.17 ± 18.14
Follow-up Mean Total Score71.39 ± 10.75
SecondarySafety of Epidiolex

Safety of Epidiolex was measured by the number of adverse events and serious adverse events that result from study drug.

Time frame:
Baseline, Follow-up (6 months)
Reported as:
Number · Events
Safety of Epidiolex
EventsCannabidiol/ Epidiolex
Number of Adverse Events that Resulted from the Study Drug24
Number of Serious Adverse Events that Resulted from the Study Drug0
SecondaryNeuroscore

Data on neurological function was collected using the Neuroscore. Data on frequency of seizures, extent of hemiparesis, assessment of visual field cut, and degree of cognitive functioning was transformed into a score from 0 to 15 where higher scores indicate worse neurologic function. Data was collected at baseline and 6 months on study drug.

Time frame:
Baseline, Follow-up (6 months)
Reported as:
Mean · score on a scale
Neuroscore
score on a scaleCannabidiol/ Epidiolex
Baseline Mean Seizure Score1.11 ± 0.33
Follow-Up Mean Seizure Score1.00 ± 0.00
Baseline Mean Hemiparesis Score1.44 ± 1.13
Follow-Up Mean Hemiparesis Score1.00 ± 0.87
Baseline Mean Visual Field Cut Score0.11 ± 0.33
Follow-Up Mean Visual Field Cut Score0.00 ± 0.00
Baseline Mean Cognitive Function Score2.33 ± 0.50
Follow-up Mean Cognitive Function Score1.44 ± 0.53
Baseline Mean Composite Score5.00 ± 1.32
Follow-up Mean Composite Score3.44 ± 0.88
SecondaryPort-wine Birthmark Score

Data on facial port-wine birthmarks was collected using the Port-wine Birthmark Score. Data on percent of face covered, thickness of birthmark, and darkness of birthmark color was collected and transformed into a score from 0 to 43 where higher scores indicate greater severity and greater surface area involved. Data was collected at baseline and 6 months on study drug.

Time frame:
Baseline, Follow-up (6 months)
Reported as:
Mean · score on a scale
Port-wine Birthmark Score
score on a scaleCannabidiol/ Epidiolex
Baseline Mean Total Score8.56 ± 3.09
Follow-up Mean Total Score8.11 ± 3.18
SecondaryAdult Neurological Quality of Life (Neuro-QoL)

Data on cognitive function was collected using Neurological Quality of Life scales from the NIH Toolbox. Data on frequency of an event was collected and transformed into a t-score from 0 to 100. Higher t-scores indicate better communication, better ability to participate in social activity, worse anxiety, worse depression, worse emotional and behavioral dyscontrol, worse fatigue, better positive affect, worse sleep disturbance, better lower and upper extremity functions, worse stigma, better satisfaction with social roles, and better cognitive function. T-score of 50 indicates the population mean with a standard deviation of 10. Data was collected at baseline and 6 months on study drug.

Time frame:
Baseline, Follow-up (6 months)
Reported as:
Mean · T-score
Adult Neurological Quality of Life (Neuro-QoL)
T-scoreCannabidiol/ Epidiolex
Baseline Mean Adult Score for Anxiety46.77 ± 13.33
Follow-Up Mean Adult Score for Anxiety46.87 ± 6.45
Baseline Mean Adult Score for Depression42.70 ± 10.05
Follow-Up Mean Adult Score for Depression44.23 ± 9.53
Baseline Mean Adult Score for Fatigue45.23 ± 9.53
Follow-Up Mean Adult Score for Fatigue42.80 ± 4.60
Baseline Mean Adult Score for Upper Extremity Function48.97 ± 8.37
Follow-Up Mean Adult Score for Upper Extremity Function53.80 ± 0.00
Baseline Mean Adult Score for Lower Extremity Function58.60 ± 0.00
Follow-Up Mean Adult Score for Lower Extremity Function58.60 ± 0.00
Baseline Mean Adult Score for Cognitive Function47.03 ± 15.52
Follow-Up Mean Adult Score for Cognitive Function46.73 ± 5.01
Baseline Mean Adult Score for Emotional and Behavioral Dyscontrol51.10 ± 14.97
Follow-Up Mean Adult Score for Emotional and Behavioral Dyscontrol41.37 ± 9.98
Baseline Mean Adult Score for Well-being54.30 ± 4.91
Follow-Up Mean Adult Score for Well-being55.70 ± 6.59
Baseline Mean Adult Score for Sleep Disturbances47.03 ± 7.49
Follow-Up Mean Adult Score for Sleep Disturbances43.93 ± 4.90
Baseline Mean Adult Score for Participation in Social Activities53.00 ± 7.41
Follow-Up Mean Adult Score for Participation in Social Activities51.03 ± 8.01
Baseline Mean Adult Score for Satisfaction in Social Activities47.70 ± 3.28
Follow-Up Mean Adult Score for Satisfaction in Social Activities49.23 ± 2.54
Baseline Mean Adult Score for Stigma53.90 ± 8.80
Follow-Up Mean Adult Score for Stigma56.47 ± 6.25

Adverse events

Collected over 6 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cannabidiol/ Epidiolex0/10 (0%)0/10 (0%)7/10 (70%)
Most frequent other events
Showing 10 of 12
Most frequent other events
EventCannabidiol/ Epidiolex
DiarrheaGastrointestinal disorders2/10
DizzinessEar and labyrinth disorders2/10
FatigueMetabolism and nutrition disorders2/10
HeadacheNervous system disorders2/10
Increased alanine aminotransferaseHepatobiliary disorders2/10
Increased aspartate aminotransferaseHepatobiliary disorders2/10
NauseaGastrointestinal disorders2/10
Darkening of port-wine birthmarkSkin and subcutaneous tissue disorders1/10
Decreased appetiteMetabolism and nutrition disorders1/10
Irritable moodPsychiatric disorders1/10

Baseline characteristics

Age, Continuous
Age, Continuous(years)Cannabidiol
Mean13.83 ± 9.67
Sex: Female, Male
Sex: Female, Male(Participants)Cannabidiol
Female6
Male4
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Cannabidiol
Hispanic or Latino2
Not Hispanic or Latino7
Unknown or Not Reported1
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Cannabidiol
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander1
Black or African American0
White6
More than one race2
Unknown or Not Reported1
Region of Enrollment
Region of Enrollment(participants)Cannabidiol
United States10
Brain Involvement
Brain Involvement(Participants)Cannabidiol
Right-Sided Brain Involvement6
Left-Sided Brain Involvement2
Bilateral Brain Involvement2
Skin Involvement
Skin Involvement(Participants)Cannabidiol
Right-Sided Skin Involvement4
Left-Sided Skin Involvement2
Bilateral Skin Involvement4
Eye Involvement
Eye Involvement(Participants)Cannabidiol
Right-Sided Eye Involvement4
Left-Sided Eye Involvement2
Bilateral Eye Involvement1
No Eye Involvement3
07

Study locations

1 site
  • Kennedy Krieger Institute
    Baltimore, Maryland 21205, United States
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Jun 29, 2021

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT04447846
Lead sponsor
Anne Comi, MD
Collaborators
Jazz Pharmaceuticals, Faneca 66 Foundation
Responsible party
Anne Comi, MD (Principal Investigator, Director Sturge-Weber Center, Kennedy Krieger Institute, Professor Johns Hopkins University School of Medicine, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.) — Sponsor-investigator
First posted
Jun 25, 2020
Start date
Oct 14, 2019
Primary completion
Aug 16, 2021
Completion
Dec 9, 2022
Results posted
May 25, 2023
Last update
May 25, 2023

Study contacts

Anne M Comi, MD
principal investigator · Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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