Functional Imaging of Tremor Circuits and Mechanisms of Treatment Response
Status:
Completed
Trial end date:
2017-04-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 4
Details
Lead Sponsor:
University of California, San Diego
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)