Ethanol Response in Essential Tremor: Clinical and Neurophysiological Correlates
| Status: | Completed |
|---|---|
| Healthy: | No |
| Age Range: | 21 - Any |
| Updated: | 4/6/2019 |
| Start Date: | August 30, 2010 |
| End Date: | January 4, 2017 |
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.
- 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.
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.
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.
- INCLUSION CRITERIA:
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)
EXCLUSION CRITERIA:
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
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.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Click here to add this to my saved trials
