Trial of Cannabis for Essential Tremor

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

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.

Study Overview

• Status: Completed
• Conditions: Essential Tremor
• Intervention / Treatment: Drug: CBD/THC; Drug: Placebo oral capsule

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • University of California San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CBD/THC; Treatment arm consisting of Tetrahydrocannabinol (5mg/capsule) and Cannabidiol (100mg/capsule).	Drug: CBD/THC; Oral formulation of combined Cannabidiol (CBD) and Tetrahydrocannabinol (THC).; Other Names: cannabidiol; cannabis; marijuana; tetrahydrocannabinol
Placebo Comparator: Placebo; Matched placebo capsule with no active ingredients.	Drug: Placebo oral capsule; Matched Placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Collaborators: Center for Medicinal Cannabis Research; Tilray; International Essential Tremor Foundation
• Investigators: Principal Investigator: Fatta Nahab, MD, UCSD

Publications and helpful links

Helpful Links

• Study Information

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2019
• Primary Completion (Actual): September 1, 2020
• Study Completion (Actual): November 30, 2020

Study Registration Dates

• First Submitted: January 9, 2019
• First Submitted That Met QC Criteria: January 11, 2019
• First Posted (Actual): January 16, 2019

Study Record Updates

• Last Update Posted (Actual): October 13, 2022
• Last Update Submitted That Met QC Criteria: October 9, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesias; Tremor; Essential Tremor; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Psychotropic Drugs; Anticonvulsants; Hallucinogens; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Dronabinol; Cannabidiol
• Other Study ID Numbers: 180414

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No