Novel Cognitive Treatment Targets for Epidiolex in Sturge- Weber Syndrome

• ClinicalTrials.gov Identifier: NCT04447846
• Recruitment Status: Completed
• First Posted: June 25, 2020
• Last Update Posted: February 15, 2022
• Sponsor: Anne Comi, MD
• Collaborators: Jazz Pharmaceuticals; Faneca 66 Foundation
• Information provided by (Responsible Party): Anne Comi, MD, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Study Description

Brief 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).

Condition or disease	Intervention/treatment	Phase
Sturge-Weber Syndrome	Drug: Cannabidiol	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Novel Cognitive Treatment Targets for Epidiolex in Sturge- Weber Syndrome: A Phase II Trial
• Actual Study Start Date: October 14, 2019
• Actual Primary Completion Date: August 16, 2021
• Actual Study Completion Date: August 16, 2021

Arms and Interventions

Arm

Intervention/treatment

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; 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.; Other Names: Epidiolex; CBD

Outcome Measures

Primary Outcome Measures :

1. Change in List Sorting Working Memory [ Time Frame: 6 months ]
   Data on cognitive function will be collected using the List Sorting Working Memory Test from the NIH Toolbox. Data will be collected on working memory performance, which will be transformed into a t-score from 0 to 100 where a higher t-score indicates better performance. Data will be collected at baseline and after 6 months on study drug. The outcome measure for the List Sorting Working Memory Test will be the significant difference between t-scores from 6 months on study drug relative to baseline

Secondary Outcome Measures :

1. Change in Picture Vocabulary [ Time Frame: 6 months ]
   Data on cognitive function will be 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 will be transformed into a t-score from 0 to 100 where a higher t-score indicates better performance. Data will be collected at bassline and after 6 months on study drug. The outcome measure for Picture Vocabulary will be the significant difference between t-scores from 6 months on study drug relative to baseline.
2. Change in seizure frequency [ Time Frame: 6 months ]
   Change in seizure frequency by seizure score at pre-treatment baseline and after six months.
3. Change in migraine severity [ Time Frame: 6 months ]
   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. Data will be collected at baseline and after 6 months on study drug. The outcome measure for migraine severity will be the percent change from six months on study drug relative to baseline.
4. Change in Modified House Classification scores [ Time Frame: 6 months ]
   Data on motor function will be collected using a Modified House Classification. Data will be collected on the ability to complete a task with the subject's non-dominant hand which will be transformed into a score from 1 to 8 and 0 to 32 where higher scores indicate better motor function. Data will be collected at baseline and after 6 months on study drug. The outcome measure for Modified House Classification will be the percent change from six months on study drug relative to baseline.
5. Change in Erhardt Developmental Prehension Assessment scores [ Time Frame: 6 months ]
   Data on motor function will be collected using the Erhardt Developmental Prehension assessment. Data will be collected on the ability to complete a task with each hand, which will be scored as age equivalence of task performance (in months). Higher scores indicate better motor function. Data will be collected at baseline and after 6 months on study drug. The outcome measure for Erhardt Developmental Prehension assessment will be the percent change from six months on study drug relative to baseline.
6. Change in Pediatric Evaluation of Disability Inventory Computer Adapted Test scores [ Time Frame: 6 months ]
   Data on motor function will be collected using the Pediatric Evaluation of Disability Inventory Computer Adapted Test. Data will be collected on the subject's ability to complete tasks involved in daily activities, mobility, and social/ cognitive activities. The data will be transformed into scaled scores ranging from 20 to 80, where higher scores indicate better motor function. Data will be collected at baseline and after 6 months on study drug. The outcome measure for the Pediatric Evaluation of Disability Inventory Computer Adapted Test will be the percent change from six months on study drug relative to baseline.
7. Change in ABILHAND score [ Time Frame: 6 months ]
   Data on motor function will be collected using the ABILHAND questionnaire, a measure of manual ability for adults with upper limb impairments. Data will be collected on the subject's ability to complete daily activities that involve the upper limbs. The data will be transformed into a logit, a linear unit that expresses the odds of success of the patient completing a task. Higher scores indicate better motor function. Data will be collected at baseline and after 6 months on study drug. The outcome measure for ABILHAND will be the percent change from six months on study drug relative to baseline.
8. Change in Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V) [ Time Frame: 6 months ]
   Data on cognitive function will be collected using the Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V). Data will be collected on working memory and processing speed performance, which will be transformed into a t-score from 0 to 100 where a higher t-score indicates better performance. Data will be collected at baseline and 6 months on study drug. The outcome measure for the Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V) will be the significant difference between t-scores from 6 months on study drug relative to baseline.
9. Change in Neurological Quality of Life (Neuro-QoL) [ Time Frame: 6 months ]
   Data on cognitive function will be collected using Neurological Quality of Life scales from the NIH Toolbox. Data on frequency of an event (e.g. forgetting schoolwork) will be collected and transformed into a t-score from 0 to 100 where higher t-scores indicate better cognitive function. Data will be collected at baseline and 6 months on study drug. The outcome measure for Neurological Quality of Life will be the significant difference between t-scores from 6 months on study drug relative to baseline.
10. Change in Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2) [ Time Frame: 6 months ]
    Data on executive function will be collected using the Behavior Rating Inventory of Executive Function, Second Edition. Data on the frequency of an event (e.g. becomes upset too easily) will be collected and transformed into a t-score from 0 to 100 where higher scores indicate greater impairment in executive function. Data will be collected at baseline and 6 months on study drug. The outcome measure for Behavioral Rating Inventory of Executive Function will be the significant difference between t-scores from 6 months on study drug relative to baseline.
11. Change in Social Responsiveness Scale, Second Edition (SRS-2) [ Time Frame: 6 months ]
    Data on social function will be 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 will be collected and transformed into a t-score from 0 to 100 where higher scores indicate greater impairment in social function. Data will be collected at baseline and 6 months on study drug. The outcome measure for Social Responsiveness Scale will be the significant difference between t-scores from 6 months on study drug relative to baseline.
12. Change in Behavioral Assessment System for Children, Third Edition (BASC-3) [ Time Frame: 6 months ]
    Data on behavioral function will be collected using the Behavioral Assessment System for Children, Third Edition (BASC-3). Data on the frequency of a behavior (e.g. avoids eye contact) will be collected and transformed into a t-score from 0 to 100 where higher scores indicate strength in a particular behavior. Data will be collected at baseline and 6 months on study drug. The outcome measure for Behavioral Assessment System for Children will be the significant difference between t-scores from 6 months on study drug relative to baseline.
13. Change in Screen for Child Anxiety Related Disorders (SCARED) [ Time Frame: 6 months ]
    Data on anxiety will be collected using the Screen for Child Anxiety Related Disorders (SCARED). Data on the truthfulness of a statement (e.g. I am nervous) will be collected and transformed into a score from 0 to 82 where higher scores indicate greater anxiety. Data will be collected at baseline and 6 months on study drug. The outcome measure for Screen for Child Anxiety Related Disorders (SCARED) will be the percent change in score from 6 months on study drug relative to baseline.
14. Change in Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) [ Time Frame: 6 months ]
    Data on quality of life will be 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) will be collected and transformed into a score from 0 to 100 where higher scores reflect better quality of life. Data will be collected at baseline and 6 months on study drug. The outcome measure for Quality of Life in Childhood Epilepsy Questionnaire will be the percent change in score from 6 months on study drug relative to baseline.
15. Safety of Epidiolex [ Time Frame: 6 months ]
    Safety of Epidiolex will be measured by the number of adverse events and serious adverse events that result from study drug.
16. Change in Neuroscore [ Time Frame: 6 months ]
    Data on neurological function will be collected using the Neuroscore. Data on frequency of seizures, extent of hemiparesis, assessment of visual field cut, and degree of cognitive functioning will be transformed into a score from 0 to 15 where higher scores indicate worse neurologic function. Data will be collected at baseline and 6 months on study drug. The outcome measure for Neuroscore will be the percent change in score from 6 months on study drug relative to baseline.
17. Change in Port-wine Birthmark Score [ Time Frame: 6 months ]
    Data on facial port-wine birthmarks will be collected using the Port-wine Birthmark Score. Data on percent of face covered, thickness of birthmark, and darkness of birthmark color will be collected and transformed into a score from 0 to 43 where higher scores indicate greater severity and greater surface area involved. Data will be collected at baseline and 6 months on study drug. The outcome measure for Port-wine Birthmark score will be percent change in score from 6 months on study drug relative to baseline.

Eligibility Criteria

• Ages Eligible for Study: 3 Years to 50 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Maryland

Kennedy Krieger Institute

Baltimore, Maryland, United States, 21205

Sponsors and Collaborators

Anne Comi, MD

Jazz Pharmaceuticals

Faneca 66 Foundation

Investigators

• Principal Investigator: Anne M Comi, MD; Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

More Information

Additional Information:

Hunter Nelson Sturge-Weber Center Website 

• 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.
• ClinicalTrials.gov Identifier: NCT04447846
• Other Study ID Numbers: IRB00204427
• First Posted: June 25, 2020
• Last Update Posted: February 15, 2022
• Last Verified: February 2022

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

Keywords provided by Anne Comi, MD, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.:

Sturge-Weber Syndrome; SWS; Cognitive impairments

Additional relevant MeSH terms:

Sturge-Weber Syndrome; Brain Stem Infarctions; Klippel-Trenaunay-Weber Syndrome; Syndrome; Disease; Pathologic Processes; Brain Infarction; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Vascular Diseases; Cardiovascular Diseases; Infarction; Ischemia; Necrosis; Angiomatosis; Hemangioma; Neoplasms, Vascular Tissue; Neoplasms by Histologic Type; Neoplasms; Neurocutaneous Syndromes; Cannabidiol; Anticonvulsants