Essential TremorPhase 4NCT02495883
Functional Imaging of Tremor Circuits and Mechanisms of Treatment Response
A Phase 4 study testing Ethanol and Propranolol in people with Essential Tremor and Tremor, run by University of California, San Diego at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 years and olderHealthy volunteers can take part
- Conditions the study is for
- Essential Tremor, Tremor
- What is being tested?
- Ethanol and Propranolol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2013to Apr 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Diego
La Jolla, California, 92037
About this study
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.
Read more
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
- Being tested
- Ethanol, Propranolol
- Keywords
- Essential Tremor, Magnetic Resonance Imaging, Therapy, Alcohol, Propranolol
- Medical subject headings
- Essential Tremor, Tremor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EthanolOther
50ml of 40% Ethanol
PropranololDrug
Also called Propranolol SR, Inderal LA
Beta blocker
| Study group | Role | What they receive |
|---|---|---|
| Essential Tremor Group | Other | Patients will be randomized to start in one of two treatment arms: 1) 50ml of 40% ethanol or 2) Propranolol SR 60-120mg. In patients who receive ethanol first, they will return for a second visit when they will receive Propranolol, and vice versa. Ethanol will be administered to participants diagnosed with Essential Tremor during the study visit, whereas patients receiving Propranolol SR will be administered daily over an estimated period of two weeks prior to the fMRI visit. Receives: Other: Ethanol; Drug: Propranolol |
| Health Volunteer Group | No intervention | Healthy Volunteers will receive no interventions. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Regions With fMRI Differences Between ET and Controls
Regions that were differentially activated in ET as measured by number of statistically significant voxels (cluster size). This represents the number of activated voxels seen in the ET group that were not present in the Healthy Control group.
Measured: At visit 1 or 2 based on randomization table.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2015 (estimated)
- Study startDec 2013
- Primary completionApr 2017
- Study completionApr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Essential TremorStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fatta B Nahab, University of California, San Diego
- Investigators
- Fatta B Nahab, MD, Principal investigator, UCSD
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02495883
- Sponsor's protocol ID
- 131202
- Other IDs
- 1R01NS073683-01A1
- Status last verified
- Dec 2020
- First submitted
- 26 Sep 2013
- Last updated
- 2 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Functional Imaging of Tremor Circuits and Mechanisms of Treatment Response
- ClinicalTrials.gov ID
- NCT02495883
- Acronym / sponsor ID
- 131202
- Conditions
- Essential Tremor, Tremor
- Keywords
- Essential Tremor, Magnetic Resonance Imaging, Therapy, Alcohol, Propranolol
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Dec 2013 (actual)
- Primary completion
- Apr 2017 (actual)
- Study completion
- Apr 2017 (actual)
- First posted
- 13 Jul 2015 (estimated)
- Results
- Posted 2 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Essential Tremor Group | Other | Other: Ethanol, Drug: PropranololPatients will be randomized to start in one of two treatment arms: 1) 50ml of 40% ethanol or 2) Propranolol SR 60-120mg. In patients who receive ethanol first, they will return for a second visit when they will receive Propranolol, and vice versa. Ethanol will be administered to participants diagnosed with Essential Tremor during the study visit, whereas patients receiving Propranolol SR will be administered daily over an estimated period of two weeks prior to the fMRI visit. |
| Health Volunteer Group | No intervention | –Healthy Volunteers will receive no interventions. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ethanol50ml of 40% Ethanol | Other | Essential Tremor Group |
| PropranololAlso: Propranolol SR, Inderal LABeta blocker | Drug | Essential Tremor Group |
Primary outcome
Regions With fMRI Differences Between ET and Controls
Time frame: At visit 1 or 2 based on randomization table.
Regions that were differentially activated in ET as measured by number of statistically significant voxels (cluster size). This represents the number of activated voxels seen in the ET group that were not present in the Healthy Control group.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fatta B Nahab, MD principal investigator
UCSD
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ethanol and Propranolol in people with Essential Tremor and Tremor, run by University of California, San Diego at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Regions With fMRI Differences Between ET and Controls (time frame: At visit 1 or 2 based on randomization table.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2020.