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

• ClinicalTrials.gov Identifier: NCT04423341
• Recruitment Status: Completed
• First Posted: June 9, 2020
• Last Update Posted: November 2, 2021
• Sponsor: Silkiss Eye Surgery
• Collaborators: Benign Essential Blepharospasm Research Foundation; Jazz Pharmaceuticals; 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. Patients will undergo videorecording with a high resolution videocamera system at days 0, 45, 90, 135, and 180 using a novel blink analysis to gather objective data measurements of changes induced by CBD in Blepharospasm patients. 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)
• Actual 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
• Actual Primary Completion Date: March 22, 2021
• Actual Study Completion Date: October 1, 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. Eyeblink analysis from high speed videocamera recordings - see separate outcome measures [ Time Frame: 4 measurements over 6 months ]
   All patients will undergo video recording of their eyelid kinematics at days 0, 45, 90, 135, and 180. A high-resolution commercially available video camera will capture the eyelid positions at a sampling rate of thirty frames per second. Patients will be assessed in three different lighting conditions - in regular exam room lighting, under examination with the glare source of an indirect ophthalmoscope (at 2000 lux on both eyes from 5 feet), and in dim lighting. The upper and lower eyelid positions captured from each frame of the videos will be input into custom software developed by Visage Technologies, which fits a feature template to the facial features in each frame, including the upper and lower lids of each eye. The difference between the upper and lower lid positions defined the lid aperture, also known as the palpebral fissure. The eyeblink parameters will then calculated from the eyelid aperture time series with custom software written in MATLAB.
2. Median Blink Amplitude [ Time Frame: 4 measurements over 6 months ]
   Measured in millimeters (mm)

Secondary Outcome Measures :

1. Median Blink Duration [ Time Frame: 4 measurements over 6 months ]
   Measured in milliseconds (ms)
2. Median Max Blink Velocity [ Time Frame: 4 measurements over 6 months ]
   Measured in millimeters per milliseconds (mm/ms)
3. Number of Blinks per 100ms [ Time Frame: 4 measurements over 6 months ]
   Total "blinks" in 100 milliseconds (numeric value)

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

Jazz Pharmaceuticals

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: November 2, 2021
• Last Verified: October 2021

• 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; Eyeblink analysis; Videorecording; Blepharospasm; BEB

Additional relevant MeSH terms:

Blepharospasm; Eyelid Diseases; Eye Diseases; Cannabidiol; Anticonvulsants