Functional Imaging of Tremor Circuits and Mechanisms of Treatment Response

Essential Tremor (ET) is the most common tremor disorder, currently affecting an estimated 2.9 million Americans and leading to disability and decreased quality of life in 75% of cases. The pathophysiology of ET is poorly understood, with the source of the tremor remaining controversial since all studies show increased activity in the cerebellum (including mimicked tremor in controls), while animal models of ET using harmaline and a single human PET study implicate the inferior olivary nucleus in the brainstem.

There is evidence from the investigator's laboratory that the use of resting-state functional magnetic resonance imaging (rs-fMRI) is useful for characterizing the abnormal tremor neural network in ET compared with controls. The goal is to identify the source of the tremor, which is hypothesized to remain active during rest.

Current ET diagnostic criteria require the presence of postural and/or kinetic tremor, which are assumed to be different manifestations of the same tremor oscillator. This long-standing assumption may be incorrect based on several lines of evidence from the investigator's laboratory, and has major implications for understanding ET pathophysiology and treatment. The investigators will test the hypothesis that postural and kinetic tremors are generated through different neural mechanisms.

Treatment of ET focuses on pharmacological agents of various mechanisms and rarely deep brain stimulation of the Vim thalamus. Despite the assortment of agents used to treat ET, only ~50% of patients benefit from a particular agent. Furthermore, the mechanisms of action on tremor are not generally known. Understanding the mechanisms of action of various tremor-suppressing agents is critical for future drug development. In this proposal, the investigators plan to study the effects of ethanol (the most efficacious tremor-suppressant currently available) and propranolol (a non-specific β-adrenergic blocker with proven efficacy and unknown mechanism of action) on the tremor neural network.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Essential Tremor Central Nervous System Diseases Dyskinesias Movement Disorders Nervous System Diseases Neurologic Manifestations Pathological Conditions, Signs and Symptoms Signs and Symptoms Tremor

Age range

21 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

University of California, San Diego

La Jolla, California, 92037, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Diagnosed with ET by a Movement Disorder Neurologist.
Tremors that improve with alcohol.
Ability to abstain from drinking alcohol or caffeine for at least 2 days before both the screening and fMRI visits
Over the age of 21.

Exclusion criteria

Significant non-ET related abnormal findings during neurological exam.
Presence of a tremor at rest.
Pregnant or nursing.
Unable to safely undergo MRI based on completion of a safety questionnaire.
History of dementia, brain tumor, stroke, head trauma or a vascular malformation based on history or MRI findings.
Severe active medical condition, such as cardiovascular disease, that prevents subject from lying flat for up to 120 minutes.
Unable or unwilling to provide informed consent.
Claustrophobia (a fear of tight spaces) or other restrictions that prevent subject from undergoing an MRI in a confined space for up to 120 minutes.
Unable to temporarily stop taking medications that may influence liver metabolism or brain function.
Tremors so severe that subject cannot safely and effectively undergo MRI
Past/current problems with alcohol abuse or dependence.
Unwillingness to take alcohol (ethanol), which is a potentially intoxicating drug
History of deep brain stimulation or thalamotomy surgery.
Sinus bradycardia, bronchial asthma, or a known allergy to propranolol (Inderal).

Treatment and study plan

Ethanol

Other

50ml of 40% Ethanol

Propranolol

Drug

Beta blocker

Other names: Propranolol SR, Inderal LA

Primary outcomes

Regions With fMRI Differences Between ET and Controls

Time frame: At visit 1 or 2 based on randomization table.

Regions that were differentially activated in ET as measured by number of statistically significant voxels (cluster size). This represents the number of activated voxels seen in the ET group that were not present in the Healthy Control group.

Sponsors and collaborators

Lead sponsor

University of California, San Diego

Other

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

Registry information

Important dates

Study start: 2013
Primary completion: 2017
Study completion: 2017
First posted: Jul 13, 2015
Registry last updated: Dec 2, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed