Trial of Cannabis for Essential Tremor

Study Overview
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Brief Summary
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This is a pilot trial to evaluate the safety and efficacy of a combined oral formulation of THC and CBD in patients with Essential Tremor.

Detailed Description
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Essential tremor (ET) is the most common neurological movement disorder, affecting up to 1% of the population and up to 5% of individuals over the age of 65. ET is characterized by often disabling tremors that occur when an individual moves. The tremors most commonly affect the hands, head, voice, and legs in order of frequency, leading to impairment in activities of daily living and morbidity. No pharmacological agent has been developed for ET, though existing agents such as propranolol and primidone are used off-label to reduce tremor amplitude. Deep brain stimulation surgery is often reserved for only individuals with the most severe tremors. Patients with ET have long reported tremor benefits with the use of cannabis, though no controlled trials have been conducted. The investigators plan to conduct the first double-blind, placebo-control clinical trial of cannabis in an oral capsule. Various validated tremor rating methods will be used to quantify tremor severity, while looking at tolerability and safety.

Official Title
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A Double-Blind, Cross-Over, Placebo- Controlled Efficacy and Tolerability Study of Oral Cannabidiol (CBD) and Tetrahydrocannabinol (THC) for Essential Tremor (ET).

Conditions
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Essential Tremor

Intervention / Treatment
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* Drug: CBD/THC
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of ET by a Movement Disorder Neurologist Stable dose of tremor medication for a period of at least 6 weeks prior to screening Tremor in the arms Tremor(s) is/are moderately severe (amplitude of at least 1cm) Exclusion Criteria: Significant non-ET related abnormal findings on neurological exam Tremor at rest, or other features suggestive of Parkinson disease Diagnosis of dementia Pregnant or nursing Childbearing potential and unable or unwilling to use contraception during course of the trial On medications known to interact with the study drug Current or prior history of alcohol or substance abuse Recent exposure to primidone (within the past 21 days) or benzodiazepines (such as Valium, Ativan or Klonopin), ketoconazole, ritonavir, clarithromycin, rifampin, carbamazepine, St. Johns Wort, digoxin or other medications known to affect your liver enzymes (within the past 7 days). Unwilling to abstain from consuming grapefruits, grapefruit juice or grapefruit containing products. Taking medications such as warfarin, cyclosporine, and amphotericin B that are highly protein-bound Do not wish to take a cannabis-derived agent Allergy or sensitivity to sorbitol, xylitol, stevia or other natural sweeteners Allergy or sensitivity to cannabis Used cannabis or a cannabis-derived product (such as CBD oil) within the past 4 weeks or plan to use it during this research study. Diagnosis of a psychiatric disorder (e.g., mania, bipolar depressive disorder, schizophrenia, schizoaffective disorder, or other major psychiatric disorder) Current or prior history of suicidal thoughts and/or behavior Active medical problem affecting the immune system, liver, gastrointestinal tract, lungs, heart, endocrine system (such as diabetes and/or thyroid), and/or a blood clotting disorder Current infection Reduced kidney function (GFR <60)

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CBD/THC<br>Treatment arm consisting of Tetrahydrocannabinol (5mg/capsule) and Cannabidiol (100mg/capsule). | Drug: CBD/THC<br>* Oral formulation of combined Cannabidiol (CBD) and Tetrahydrocannabinol (THC).<br>* Other names: tetrahydrocannabinol;|
| Placebo Comparator: Placebo<br>Matched placebo capsule with no active ingredients. | Drug: Placebo oral capsule<br>* Matched Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Digital Spirography | The tremor mean amplitude calculated using computerized spirography to measure kinetic tremors. | Day 22 (100 minutes post-dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Score on a Scale From Baseline of the Tremor Research Group Essential Tremor Rating Scale (TETRAS) | The performance sub scale of the TETRAS will be used to measure tremor severity. The scale ranges from 0 to 60 points (0 being no tremor). | Baseline and Day 22 | 
| Global Impression of Change | The Global impression of change will be calculated based on both physician and patient report. The scale ranges from a score of 1 (very much improved) to 7 (very much worse) with a score of 4 indicating 'no change'. | Day 22 | 
| Number of Participants Reporting Adverse Events Based on Common Terminology Criteria | Side effects survey | Days 1, 3, 6, 22 | 
| Number of Participants at Risk for Suicide Based on Columbia-Suicide Severity Rating Scale (C-SSRS) | This is a scale looking at risk assessment of suicidality. The presence of any positive responses will lead to further evaluation. | Day 22 | 
| Number of Participants With New Study-related Electrocardiogram (EKG) Abnormalities | Electrocardiographic changes from baseline measures will trigger further evaluation. EKG's will be rated as normal/abnormal relative to the baseline EKG reading, and abnormal findings will be rated as clinically significant/not clinically significant. | Day 22 | 
| Accelerometry-based Assessment of Tremor Severity | The spectral power density measure of accelerometry data to measure will serve as a measure of tremor severity, comparing tremor amplitude from this digital biomarker at the time of the primary outcome to the same measure at baseline. | Baseline and Day 22 |