Effect of Non-psychoactive Cannabidiol as an Adjunct to Botulinum Toxin in Blepharospasm

• ClinicalTrials.gov Identifier: NCT04423341
• Recruitment Status: Enrolling by invitation
• First Posted: June 9, 2020
• Last Update Posted: June 9, 2020
• Sponsor: Silkiss Eye Surgery
• Collaborators: Benign Essential Blepharospasm Research Foundation; GW Pharmaceuticals Ltd.; Smith-Kettlewell Eye Research Institute
• Information provided by (Responsible Party): Rona Silkiss, MD FACS, Silkiss Eye Surgery

Study Description

Brief Summary:

The planned study is a prospective analysis of non-psychoactive Cannabidiol (without THC) as an adjunctive therapy for blepharospasm in a masked double cross-over study. This prospective study is a follow-up to a retrospective study completed by the researchers using over-the-counter, self purchased CBD. This study will use FDA approved Cannabidiol medication, Epidiolex, directly from GW pharmaceuticals, rather than self-purchased CBD from the internet. Additionally, patients will undergo EEG monitoring via a Blink-EEG protocol for objective data measurements of changes induced by CBD in Blepharospasm patients. Independent second measures will be of blink kinematic analysis of review of video recording. Results would also be correlated with the Blepharospasm Severity Disability Index, Modified CDQ-24 scale and Jankovic Rating Scale. To assess any change in anxiety that might be relevant to therapeutic effect, the anxiety scale GAD-7 survey will also be administered and correlated with the results. This study will attempt to codify the data and quantify if adjunctive CBD therapy improves those areas compared to botulinum injection alone.

Condition or disease	Intervention/treatment	Phase
Blepharospasm; Blepharospasm, Benign Essential; CBD	Drug: Cannabidiol Oral Solution [Epidiolex]	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of Non-psychoactive Cannabidiol as an Adjunct to Botulinum Toxin in Blepharospasm - a Prospective Double-masked Cross-over Study
• Actual Study Start Date: May 20, 2020
• Estimated Primary Completion Date: February 2021
• Estimated Study Completion Date: February 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Group A - active medication followed by placebo	Drug: Cannabidiol Oral Solution [Epidiolex]; 100 mg BID for three months Placebo oral solution for three months
Active Comparator: Group B - placebo followed by active medication	Drug: Cannabidiol Oral Solution [Epidiolex]; 100 mg BID for three months Placebo oral solution for three months

Outcome Measures

Primary Outcome Measures :

1. EEG/EOG measurements [ Time Frame: 4 times over 6 months ]
   EEG/EOG data will be recorded using an EGI Geodesic Netstation high-density, whole head recording system (Electrical Geodesics, Inc., Eugene, OR) using 128 electrodes distributed around the head and face, with the impedance of all electrodes will be maintained below 60 kΩ according to the recommended value for this system. The data will be recorded at a sampling rate of 500 Hz and band-pass filtered between 0.01 and 250 Hz, with the recorded signals for all electrodes being referenced to the vertex electrode. The results wills be measured in μV deflections over time. The results will be assessed for change at each time point over 6 months.
2. Jankovic Rating Scale [ Time Frame: 4 times over 6 months ]

   The Jankovic Rating Scale is a survey of Blepharospasm Severity and Frequency, each ranked numerically from 0-5 as below:

   Blepharospasm Severity 0 = None

   1. = Minimal, increased blinking present only with external stimuli (i.e., bright light or wind)
   2. = Mild, spontaneous eyelid fluttering (without active spasm). Symptoms are noticeable, possibly embarrassing, but not functionally disabling.
   3. = Moderate, very noticeable spasms of eyelids, only. Mildly incapacitating.
   4. = Severe, incapacitating spasms of eyelids and possibly other facial muscles.

   Blepharospasm Frequency 0 = None

   1. = Slightly increased frequency of blinking.
   2. = Eyelid fluttering lasting less than 1 second in duration.
   3. = Eyelid spasms lasting for more than 1 second, but eyes open more than 50% of wakeful hours.
   4. = Functionally "blind" due to persistent eyelid closure, more than 50% of the waking time

   The results will be assessed for change at each time point over 6 months.

Secondary Outcome Measures :

1. Blepharospasm Disability Index (BSDI) [ Time Frame: 4 times over 6 months ]

   The BSDI is a survey of symptoms experienced from blepharospasm for activities of daily living, ranked from 0-4 as below:

   Items:

   Reading Driving a vehicle Watching television Shopping Doing everyday activities Getting about on foot

   Ratings 0 = no impairment

   1. = mild impairment
   2. = moderate impairment
   3. = severe impairment
   4. = not possible due to severe disease Not applicable = N/A
2. Modified CDQ-24 Questionnaire [ Time Frame: 4 times over 6 months ]

   The Modified CDQ-24 Questionnaire is a series of 24 questions surveying how often a specific activity or function is affecting a person. Answers include never/occasionally/sometimes/often/always or not at all/slightly/moderately/severely/very severely.

   This is calculated by assigning scores of 1, 2, 3,4, and 5 to the response categories of "never," "occasionally," "sometimes," "often" and "always" respectively, as well as assigning scores of 1, 2, 3,4, and 5 to the response categories of "not at all," "slightly," "moderately," "severely" and "very severely" respectively.

3. Generalized Anxiety Disorder-7 [ Time Frame: 4 times over 6 months ]
   This survey asks participants how often they have been bothered by specific problems over the past two weeks. GAD-7 total score for the seven items ranges from 0 to 21. This is calculated by assigning scores of 0, 1, 2, and 3, to the response categories of "not at all," "several days," "more than half the days," and "nearly every day," respectively

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Patients in the private practice of the principal investigator with an ICD code of "blepharospasm" and:
• undergoing routine maximal botulinum therapy
• experiencing break through symptoms of spasm
• marijuana naïve

Exclusion Criteria:

• concomitant diagnosis of epilepsy
• patients whom are not marijuana naive
• patients on concurrent anti-epileptics
• patients who are pregnant or wishing to become pregnant
• patients not wishing to participate in the study.

Contacts and Locations

Locations

United States, California

Silkiss Eye Surgery

Oakland, California, United States, 94609

Sponsors and Collaborators

Silkiss Eye Surgery

Benign Essential Blepharospasm Research Foundation

GW Pharmaceuticals Ltd.

Smith-Kettlewell Eye Research Institute

More Information

• Responsible Party: Rona Silkiss, MD FACS, Physician, Silkiss Eye Surgery
• ClinicalTrials.gov Identifier: NCT04423341
• Other Study ID Numbers: 1268646
• First Posted: June 9, 2020
• Last Update Posted: June 9, 2020
• Last Verified: June 2020

• 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 Rona Silkiss, MD FACS, Silkiss Eye Surgery:

Cannabidiol; Epidiolex; Botulinum Toxin; EEG; EOG; Blepharospasm; BEB

Additional relevant MeSH terms:

Blepharospasm; Eyelid Diseases; Eye Diseases; Cannabidiol; Anticonvulsants