Functional Imaging of Tremor Circuits and Mechanisms of Treatment Response

Summary

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.

Conditions

• Essential Tremor
• Tremor

Interventions

OTHER

Ethanol

50ml of 40% Ethanol

DRUG

Propranolol

Beta blocker

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS)

  collaborator NIH

• University of California, San Diego

  lead OTHER

Principal Investigators

• Fatta B Nahab, MD · UCSD

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

21 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2013-12-31

Primary Completion

2017-04-30

Completion

2017-04-30

FDA Drug

Yes

Countries

• United States

Study Locations