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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
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Fatta B Nahab, University of California, San Diego

Brief 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.


Condition or disease Intervention/treatment Phase
Essential Tremor Tremor Other: Ethanol Drug: Propranolol Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Other
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.

Other: Ethanol
50ml of 40% Ethanol

Drug: Propranolol
Beta blocker
Other Names:
  • Propranolol SR
  • Inderal LA

No Intervention: Health Volunteer Group
Healthy Volunteers



Primary Outcome Measures :
  1. 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

  2. BOLD-fMRI Activation [ Time Frame: 30 minutes Post-Ethanol dose ]
    Functional MRI data will be collected at time-point above


Secondary Outcome Measures :
  1. The Essential Tremor Rating Assessment Scale [ Time Frame: Baseline ]
    Measurement of Tremor Severity



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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).

Information from the National Library of Medicine

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


Locations
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United States, California
University of California, San Diego
La Jolla, California, United States, 92037
Sponsors and Collaborators
University of California, San Diego
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: Fatta B Nahab, MD UCSD

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Responsible Party: Fatta B Nahab, Associate Professor of Neurosciences, University of California, San Diego
ClinicalTrials.gov Identifier: NCT02495883     History of Changes
Other Study ID Numbers: 131202
1R01NS073683-01A1 ( U.S. NIH Grant/Contract )
First Posted: July 13, 2015    Key Record Dates
Last Update Posted: January 29, 2019
Last Verified: January 2019
Keywords provided by Fatta B Nahab, University of California, San Diego:
Essential Tremor
Magnetic Resonance Imaging
Therapy
Alcohol
Propranolol
Additional relevant MeSH terms:
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Tremor
Essential Tremor
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Movement Disorders
Central Nervous System Diseases
Ethanol
Propranolol
Anti-Infective Agents, Local
Anti-Infective Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Arrhythmia Agents
Antihypertensive Agents
Vasodilator Agents