Essential TremorNCT01200966
Ethanol Response in Essential Tremor: Clinical and Neurophysiological Correlates
An observational study of Essential Tremor, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
Background: Essential tremor (ET) is a neurological disorder involving uncontrollable shaking, which over time can interfere with mobility and affect routine aspects of daily living. Several medications are used to treat ET, but these medications are often only partially effective and can have side effects. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Essential Tremor
- How many people
- 96 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Aug 2010to 4 Jan 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of essential tremor with bilateral hand tremor as the predominant feature
- Unequivocal spirographic tremor of both hands on screening examination
- Subjects must be willing and safely able to comply with the study protocol and therefore abstain from any medication for the treatment of tremor for a period of at least 5 plasma half-lives of the individual drug prior to study participation. (For Propranolol/Inderal , Gabapentin/Neurontin this will be 1 day; for Primidone/Mysoline : 26 days).
- Subjects must be willing to refrain from alcohol and drinks or food containing caffeine starting 48 hours prior to the study visit(s)
Who cannot join
- Patients with any other significant pathological finding in the neurological examination other than typical symptoms of ET
- Acute or chronic severe medical conditions which would preclude the subject from participating (e.g., severe heart disease NYHA grade 3 or 4, renal failure, hepatic failure, lung disease, uncontrolled hyperthyroidism)
- Subjects with active or past alcohol abuse or dependence
- Elevated liver function parameters (AST, ALT, GGT), higher than the 1.5 fold upper limit of the normal range (as defined by the NIH Clinical Center Laboratory Medicine Department). The limit for AST therefore will be 51 U/l, for ALT 62 U/L, and GGT 128 U/l.
- Female subjects who are pregnant or lactating
- Subjects aged < 21 years
Show all 12Show fewer
- Subjects with unable or unwilling to give informed consent
- Subjects unable or unwilling to cooperate with study requirements Use of prescription or OTC medications that interact with ethanol or influence brain excitability (e.g. hypnotic, antiepileptic, antipsychotic medication, stimulants, antihistamines, muscle relaxants, etc.).
- Known flushing symptoms after alcohol intake or allergy to alcohol.
- ADDITIONAL EXCLUSION CRITERIA FOR SUBJECTS ALSO PARTICIPATING IN PHASE 2:
- History of seizure disorder or hearing loss
- Presence of pacemaker, implanted medical pump, metal plate or metal object in skull or eye.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Background:
- Essential tremor (ET) is a neurological disorder involving uncontrollable shaking, which over time can interfere with mobility and affect routine aspects of daily living. Several medications are used to treat ET, but these medications are often only partially effective and can have side effects. About two-thirds (66%) of people with ET have some relief from drinking alcohol, which suggests that alcohol affects the part of the brain causing the tremor. However, more research is needed to better understand the effects of alcohol or what areas of the brain might be important in the response.
Read more
Objectives:
- To study to what extent alcohol is reducing tremor in a group of patients with essential tremor.
- To use transcranial magnetic stimulation to study the effects of alcohol on essential tremor.
Eligibility:
- Individuals who are at least 21 years of age, have been diagnosed with essential tremor and have tremor in both hands, and can tolerate being off all medications for essential tremor for up to 4 weeks.
Design:
- This study has one screening visit (1 to 2 hours), followed by one study visit (3 to 5 hours). Participants might be asked to also take part in one additional study visit (3 to 5 hours). The maximum period between the study visits is 3 months.
- Participants will be screened with a medical history, physical examination, and blood tests. At this visit, participants will receive information about how to safely taper off their current ET medications before the start of the study.
- Participants must be willing to abstain from drinking any alcohol or caffeine (or consuming foods with caffeine such as chocolate) for at least 2 days before the study visits. Participants must also fast overnight (for at least 8 hours) before the study visits.
- At the first study visit, participants will receive a single drink of alcohol (mixed with a noncaffeinated drink) and will complete movement tests to determine whether the alcohol improves the tremor. Alcohol levels will be monitored throughout the visit.
- At the second study visit, participants will have an electrocardiogram to measure heart electrical activity and determine if they are able to safely have transcranial magnetic stimulation. Participants will then receive an intravenous infusion of alcohol and complete questionnaires during the infusion to provide information about its effects. Then, transcranial magnetic stimulation will be used to study brain electrical activity, as well as muscle movements and tremor activity, while under the influence of the alcohol infusion.
- After each study visit, participants will remain at the clinical center until the effects of the alcohol have worn off. Participants will be able to resume taking their ET medications after the end of the study.
Read the detailed description
OBJECTIVE:
The objective of this study is to investigate the clinical and electrophysiological correlates of the ethanol response in suppressing the tremor amplitude in patients with essential tremor (ET).
STUDY POPULATION:
85 patients with clinically diagnosed ET according to published diagnostic criteria will be entered into study phase 1. From the groups of participants in study phase 1, 12 responders and 12 non-responders will be invited back to participate in study phase 2.
DESIGN:
In study phase 1, the response to ethanol will be measured by a quantitative and qualitative approach using Essential Tremor (ET) spiral analysis during a standardized oral ethanol challenge. The clinical response will be correlated to breath-alcohol levels. Participants of study phase 1 will be selected based on their rate of response - dichotomized into a group of responders vs. non-responders - for study phase 2, during an IV ethanol challenge, brain excitability will be tested using transcranial magnetic stimulation (TMS).
OUTCOME MEASURES:
As the primary outcome parameter of study phase 1, we will determine the patients who respond to ethanol by tremor reduction versus patients without reduction of tremor intensities, as measured using spiral analysis of the dominant hand. Criterion for response will be operationally defined in a dichotomized fashion as reduction of tremor intensities, larger than the known diurnal variation of ET. Therefore, a patient will be considered a responder, if spirographic tremor amplitudes decrease by 35% or more at the time-point 60 minutes after an oral ethanol administration, as compared to baseline. As secondary outcome parameters, spiral data from the non-dominant hand, as well as clinical rating scales and breath alcohol levels will be measured to correlate objective with subjective ratings of ethanol effect in ET.
In study phase two, changes of short intracortical inhibition (SICI), known to be mediated by GABAA, will be analyzed using TMS and compared between responders and non-responders before and during a constant iv administration of ethanol. Secondary outcome parameters include the measurement of changes of GABAB-mediated paradigms such as long intracortical inhibition (LICI), cortical silent period (CSP), intracortical facilitation (ICF), motor evoked potential recruitment curve as well as TMS-measures of cerebellar inhibition.
- Conditions
- Essential Tremor
- Keywords
- Essential Tremor, Transcranial Magnetic Stimulation (TMS), Ethanol, Alcohol, Alcohol Clamp, ET
- Medical subject headings
- Essential Tremor
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: To objectively determine the rate of ethanol responders vs. non-responders in a prospective sample of ET patients.
Phase 2: To evaluate changes of SICI in responding vs. non-responding ET patients during a continuous ethanol administration
Secondary outcomes (2)
Phase 1: To correlate spirographic and clinical response in both hands with breath-alcohol-levels, acquired using a Breathalyzer at constant intervals after ethanol administration.
Phase 2: To evaluate changes additional TMS measures between groups
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2010 (estimated)
- Study start30 Aug 2010
- Study completion4 Jan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Essential TremorStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The 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
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Mark Hallett, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01200966
- Sponsor's protocol ID
- 100199
- Other IDs
- 10-N-0199
- Status last verified
- 4 Jan 2017
- First submitted
- 11 Sep 2010
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
Louis ED, Ottman R, Hauser WA. How common is the most common adult movement disorder? estimates of the prevalence of essential tremor throughout the world. Mov Disord. 1998 Jan;13(1):5-10. doi: 10.1002/mds.870130105.
PubMed 9452318Deuschl G, Bain P, Brin M. Consensus statement of the Movement Disorder Society on Tremor. Ad Hoc Scientific Committee. Mov Disord. 1998;13 Suppl 3:2-23. doi: 10.1002/mds.870131303.
PubMed 9827589Wells JN, Shirodkar AV, Knevel AM. Aziridine derivatives as potential monoamine oxidase inhibitors. J Med Chem. 1966 Mar;9(2):195-7. doi: 10.1021/jm00320a009. No abstract available.
PubMed 5911798
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ethanol Response in Essential Tremor: Clinical and Neurophysiological Correlates
- ClinicalTrials.gov ID
- NCT01200966
- Acronym / sponsor ID
- 100199
- Conditions
- Essential Tremor
- Keywords
- Essential Tremor, Transcranial Magnetic Stimulation (TMS), Ethanol, Alcohol, Alcohol Clamp, ET
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 30 Aug 2010
- Study completion
- 4 Jan 2017
- First posted
- 14 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Essential tremor (ET) is a neurological disorder involving uncontrollable shaking, which over time can interfere with mobility and affect routine aspects of daily living. Several medications are used to treat ET, but these medications are often only partially effective and can have side effects. About two-thirds (66%) of people with ET have some relief from drinking alcohol, which suggests that alcohol affects the part of the brain causing the tremor. However, more research is needed to better understand the effects of alcohol or what areas of the brain might be important in the response.
Objectives:
- To study to what extent alcohol is reducing tremor in a group of patients with essential tremor.
- To use transcranial magnetic stimulation to study the effects of alcohol on essential tremor.
Eligibility:
- Individuals who are at least 21 years of age, have been diagnosed with essential tremor and have tremor in both hands, and can tolerate being off all medications for essential tremor for up to 4 weeks.
Design:
- This study has one screening visit (1 to 2 hours), followed by one study visit (3 to 5 hours). Participants might be asked to also take part in one additional study visit (3 to 5 hours). The maximum period between the study visits is 3 months.
- Participants will be screened with a medical history, physical examination, and blood tests. At this visit, participants will receive information about how to safely taper off their current ET medications before the start of the study.
- Participants must be willing to abstain from drinking any alcohol or caffeine (or consuming foods with caffeine such as chocolate) for at least 2 days before the study visits. Participants must also fast overnight (for at least 8 hours) before the study visits.
- At the first study visit, participants will receive a single drink of alcohol (mixed with a noncaffeinated drink) and will complete movement tests to determine whether the alcohol improves the tremor. Alcohol levels will be monitored throughout the visit.
- At the second study visit, participants will have an electrocardiogram to measure heart electrical activity and determine if they are able to safely have transcranial magnetic stimulation. Participants will then receive an intravenous infusion of alcohol and complete questionnaires during the infusion to provide information about its effects. Then, transcranial magnetic stimulation will be used to study brain electrical activity, as well as muscle movements and tremor activity, while under the influence of the alcohol infusion.
- After each study visit, participants will remain at the clinical center until the effects of the alcohol have worn off. Participants will be able to resume taking their ET medications after the end of the study.
Detailed description
OBJECTIVE:
The objective of this study is to investigate the clinical and electrophysiological correlates of the ethanol response in suppressing the tremor amplitude in patients with essential tremor (ET).
STUDY POPULATION:
85 patients with clinically diagnosed ET according to published diagnostic criteria will be entered into study phase 1. From the groups of participants in study phase 1, 12 responders and 12 non-responders will be invited back to participate in study phase 2.
DESIGN:
In study phase 1, the response to ethanol will be measured by a quantitative and qualitative approach using Essential Tremor (ET) spiral analysis during a standardized oral ethanol challenge. The clinical response will be correlated to breath-alcohol levels. Participants of study phase 1 will be selected based on their rate of response - dichotomized into a group of responders vs. non-responders - for study phase 2, during an IV ethanol challenge, brain excitability will be tested using transcranial magnetic stimulation (TMS).
OUTCOME MEASURES:
As the primary outcome parameter of study phase 1, we will determine the patients who respond to ethanol by tremor reduction versus patients without reduction of tremor intensities, as measured using spiral analysis of the dominant hand. Criterion for response will be operationally defined in a dichotomized fashion as reduction of tremor intensities, larger than the known diurnal variation of ET. Therefore, a patient will be considered a responder, if spirographic tremor amplitudes decrease by 35% or more at the time-point 60 minutes after an oral ethanol administration, as compared to baseline. As secondary outcome parameters, spiral data from the non-dominant hand, as well as clinical rating scales and breath alcohol levels will be measured to correlate objective with subjective ratings of ethanol effect in ET.
In study phase two, changes of short intracortical inhibition (SICI), known to be mediated by GABAA, will be analyzed using TMS and compared between responders and non-responders before and during a constant iv administration of ethanol. Secondary outcome parameters include the measurement of changes of GABAB-mediated paradigms such as long intracortical inhibition (LICI), cortical silent period (CSP), intracortical facilitation (ICF), motor evoked potential recruitment curve as well as TMS-measures of cerebellar inhibition.
Study design
- Observational model
- Cohort
- Time perspective
- Other
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of essential tremor with bilateral hand tremor as the predominant feature
- Unequivocal spirographic tremor of both hands on screening examination
- Subjects must be willing and safely able to comply with the study protocol and therefore abstain from any medication for the treatment of tremor for a period of at least 5 plasma half-lives of the individual drug prior to study participation. (For Propranolol/Inderal , Gabapentin/Neurontin this will be 1 day; for Primidone/Mysoline : 26 days).
- Subjects must be willing to refrain from alcohol and drinks or food containing caffeine starting 48 hours prior to the study visit(s)
Key exclusion criteria (12 listed)
- Patients with any other significant pathological finding in the neurological examination other than typical symptoms of ET
- Acute or chronic severe medical conditions which would preclude the subject from participating (e.g., severe heart disease NYHA grade 3 or 4, renal failure, hepatic failure, lung disease, uncontrolled hyperthyroidism)
- Subjects with active or past alcohol abuse or dependence
- Elevated liver function parameters (AST, ALT, GGT), higher than the 1.5 fold upper limit of the normal range (as defined by the NIH Clinical Center Laboratory Medicine Department). The limit for AST therefore will be 51 U/l, for ALT 62 U/L, and GGT 128 U/l.
- Female subjects who are pregnant or lactating
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Phase 1: To objectively determine the rate of ethanol responders vs. non-responders in a prospective sample of ET patients.
Phase 2: To evaluate changes of SICI in responding vs. non-responding ET patients during a continuous ethanol administration
2 secondary outcomes
Phase 1: To correlate spirographic and clinical response in both hands with breath-alcohol-levels, acquired using a Breathalyzer at constant intervals after ethanol administration.
Phase 2: To evaluate changes additional TMS measures between groups
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Background: PubMed 9452318Louis ED, Ottman R, Hauser WA. How common is the most common adult movement disorder? estimates of the prevalence of essential tremor throughout the world. Mov Disord. 1998 Jan;13(1):5-10. doi: 10.1002/mds.870130105.
- Background: PubMed 9827589Deuschl G, Bain P, Brin M. Consensus statement of the Movement Disorder Society on Tremor. Ad Hoc Scientific Committee. Mov Disord. 1998;13 Suppl 3:2-23. doi: 10.1002/mds.870131303.
- Background: PubMed 5911798Wells JN, Shirodkar AV, Knevel AM. Aziridine derivatives as potential monoamine oxidase inhibitors. J Med Chem. 1966 Mar;9(2):195-7. doi: 10.1021/jm00320a009. No abstract available.
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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.
Mark Hallett, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Essential Tremor, run by National Institute of Neurological Disorders and Stroke (NINDS) 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 12 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 17 Dec 2019. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Phase 1: To objectively determine the rate of ethanol responders vs. non-responders in a prospective sample of ET patients.. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01200966, which also lists 3 linked publications.
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 17 Dec 2019.