Functional Imaging of Tremor Circuits and Mechanisms of Treatment Response
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|ClinicalTrials.gov Identifier: NCT02495883|
Recruitment Status : Active, not recruiting
First Posted : July 13, 2015
Last Update Posted : January 29, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Essential Tremor Tremor||Other: Ethanol Drug: Propranolol||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||64 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||None (Open Label)|
|Official Title:||Functional Imaging of Tremor Circuits and Mechanisms of Treatment Response|
|Study Start Date :||July 2011|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||December 2019|
Essential Tremor Group
50ml of 40% ethanol will be administered to participants diagnosed with Essential Tremor.
Propranolol SR 60-120mg will be administered daily to participants over an estimated period of two weeks.
50ml of 40% Ethanol
No Intervention: Health Volunteer Group
- BOLD-fMRI Activation [ Time Frame: an expected average of 2 weeks post stable dose of Propranolol ]Functional MRI data will be collected at time-point above
- BOLD-fMRI Activation [ Time Frame: 30 minutes Post-Ethanol dose ]Functional MRI data will be collected at time-point above
- The Essential Tremor Rating Assessment Scale [ Time Frame: Baseline ]Measurement of Tremor Severity
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02495883
|United States, California|
|University of California, San Diego|
|La Jolla, California, United States, 92037|
|Principal Investigator:||Fatta B Nahab, MD||UCSD|