Expired Study
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La Jolla, California 92037


Purpose:

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.


Criteria:

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).


Study is Available At:


Original ID:

131202


NCT ID:

NCT02495883


Secondary ID:

1R01NS073683-01A1


Study Acronym:


Brief Title:

Functional Imaging of Tremor Circuits and Mechanisms of Treatment Response


Official Title:

Functional Imaging of Tremor Circuits and Mechanisms of Treatment Response


Overall Status:

Active, not recruiting


Study Phase:

N/A


Genders:

N/A


Minimum Age:

21 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

University of California, San Diego


Oversight Authority:

United States: Institutional Review Board


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

2


Number of Groups:

0


Total Enrollment:

64


Enrollment Type:

Actual


Overall Contact Information

Official Name:Fatta B Nahab, MD
Principal Investigator
UCSD

Study Dates

Start Date:July 2011
Completion Date:December 2019
Completion Type:Anticipated
Primary Completion Date:December 2019
Primary Completion Type:Anticipated
Verification Date:January 2019
Last Changed Date:January 27, 2019
First Received Date:September 26, 2013

Study Outcomes

Outcome Type:Secondary Outcome
Measure:The Essential Tremor Rating Assessment Scale
Time Frame:Baseline
Safety Issues:False
Description:Measurement of Tremor Severity
Outcome Type:Primary Outcome
Measure:BOLD-fMRI Activation
Time Frame:30 minutes Post-Ethanol dose
Safety Issues:False
Description:Functional MRI data will be collected at time-point above
Outcome Type:Primary Outcome
Measure:BOLD-fMRI Activation
Time Frame:an expected average of 2 weeks post stable dose of Propranolol
Safety Issues:False
Description:Functional MRI data will be collected at time-point above

Study Interventions

Intervention Type:Other
Name:Ethanol
Description:50ml of 40% Ethanol
Arm Name:Essential Tremor Group
Intervention Type:Drug
Name:Propranolol
Description:Beta blocker
Arm Name:Essential Tremor Group
Other Name:Propranolol SR

Study Arms

Study Arm Type:No Intervention
Arm Name:Health Volunteer Group
Description:Healthy Volunteers
Study Arm Type:Other
Arm Name:Essential Tremor Group
Description: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.

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:University of California, San Diego
Agency Class:NIH
Agency Type:Collaborator
Agency Name:National Institute of Neurological Disorders and Stroke (NINDS)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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