Clinical and Physiological Studies of Tremor Syndromes
| Status: | Recruiting |
|---|---|
| Conditions: | Parkinsons Disease, Neurology, Orthopedic |
| Therapuetic Areas: | Neurology, Orthopedics / Podiatry |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 2/13/2019 |
| Start Date: | May 17, 2017 |
| End Date: | January 1, 2022 |
| Contact: | Elaine P Considine, R.N. |
| Email: | considinee@ninds.nih.gov |
| Phone: | (301) 435-8518 |
Background:
Researchers have some data on how the brain controls movement and why some people have
tremor. But the causes of tremor are not fully known. Researchers want to study people with
tremor to learn about changes in the brain and possible causes of tremor.
Objective:
To better understand how the brain controls movement, learn more about tremor, and train
movement disorder specialists.
Eligibility:
People ages 18 and older with a diagnosed tremor syndrome
Healthy volunteers ages 18 and older
Design:
Participants will be screened with:
- Medical history
- Physical exam
- Urine tests
- Clinical rating scales
- Health questions
- They may have electromyography (EMG) or accelerometry. Sensors or electrodes taped to
the skin measure movement.
Participation lasts up to 1 year.
Some participants will have a visit to examine their tremor more. They may have rating
scales, EMG, and drawing and writing tests.
Participants will be in 1 or more substudies. These will require up to 7 visits. Visits could
include the following:
- EMG with accelerometry
- Small electrodes taped on the body give small electric shocks that stimulate nerves.
- MRI: Participants lie on a table that slides into a cylinder that takes pictures of the
body while they do simple tasks.
- Small electrodes on the scalp record brain waves.
- A cone with detectors on the head measures brain activity while participants do tasks.
- A wire coil held on the scalp gives an electrical current that affects brain activity.
- Tests for thinking, memory, smell, hearing, or vision
- Electrodes on the head give a weak electrical current that affects brain activity.
- Photographs or videos of movement
Participant data may be shared with other researchers.
Researchers have some data on how the brain controls movement and why some people have
tremor. But the causes of tremor are not fully known. Researchers want to study people with
tremor to learn about changes in the brain and possible causes of tremor.
Objective:
To better understand how the brain controls movement, learn more about tremor, and train
movement disorder specialists.
Eligibility:
People ages 18 and older with a diagnosed tremor syndrome
Healthy volunteers ages 18 and older
Design:
Participants will be screened with:
- Medical history
- Physical exam
- Urine tests
- Clinical rating scales
- Health questions
- They may have electromyography (EMG) or accelerometry. Sensors or electrodes taped to
the skin measure movement.
Participation lasts up to 1 year.
Some participants will have a visit to examine their tremor more. They may have rating
scales, EMG, and drawing and writing tests.
Participants will be in 1 or more substudies. These will require up to 7 visits. Visits could
include the following:
- EMG with accelerometry
- Small electrodes taped on the body give small electric shocks that stimulate nerves.
- MRI: Participants lie on a table that slides into a cylinder that takes pictures of the
body while they do simple tasks.
- Small electrodes on the scalp record brain waves.
- A cone with detectors on the head measures brain activity while participants do tasks.
- A wire coil held on the scalp gives an electrical current that affects brain activity.
- Tests for thinking, memory, smell, hearing, or vision
- Electrodes on the head give a weak electrical current that affects brain activity.
- Photographs or videos of movement
Participant data may be shared with other researchers.
Objectives:
The purpose of this protocol is to study the phenotypic spectrum and the pathophysiology of
tremor syndromes by performing small behavioral, electrophysiological and neuroimaging
sub-studies. The protocol includes techniques with minimal risk (standard clinical
evaluation, MRI, EEG, peripheral nerve stimulation, single and paired pulse TMS) and certain
sub-studies may involve healthy volunteers. This protocol aims to study neurophysiological
and behavioral outcomes in defined groups of patients with action tremor syndromes, to inform
future hypothesis-driven and confirmatory studies, which will be developed and submitted as
separate protocols. For this purpose, we aim to conduct 1) pilot sub-studies, 2) individual
patient investigations, 3) training studies for investigators, as well as 4) technical
development studies.
Study population:
We intend to up to 300 patients with essential tremor and other isolated action tremor
syndromes, as well as 150 healthy volunteers.
Design:
This is a non-hypothesis driven study involving standardized phenotyping as well as thematic
sub-studies. After patients and healthy volunteers complete a screening visit, patients will
undergo a standardized phenotyping visit including clinical rating scales as well as
electrophysiological tremor-workup. Patient and healthy controls may then be enrolled in
sub-studies, which are pertinent to the theme of this protocol. If a sub-study leads to
results of interest, a separate protocol will be submitted with a priori hypotheses, specific
study design and power analysis adapted from the pilot or exploratory sub-studies performed
in the present protocol. At any given time, no more than 5 sub-studies can be actively
accruing subjects concurrently.
Outcome measures:
Outcome measures applied in this protocol involve methods for tremor phenotyping such as
clinical rating scales and questionnaires, electrophysiological tremor studies, videotaped
exam, as well as digitizing based tasks. During the thematic studies focused on the
neurophysiological characterization of tremor syndromes, the following outcome measures will
be applied: EMG: we will analyze tremor signals using spectral analyses, coherence analyses,
and in combination with accelerometry, EEG, MEG, and TMS to explore tremor-networks. MRI: we
will analyze measures such as the amplitude of the BOLD signal (fMRI); tractography between
seed and target regions of interest (using DTI); morphometry of brain regions (using VBM);
and different neurotransmitter levels in brain regions of interest (using MRS). EEG and MEG:
we will quantify measures such as corticomuscular coherence, event- or task-related
potentials, synchronization/desynchronization, and coherence between sensors or sources
located close to the brain areas of interest. TMS: we will analyze measures such as MEP
amplitude and central conduction time, as well as measures of cortical excitability and
inhibition paradigms. Behavioral measures: we will quantify measures of voluntary movement
involving tremor, reaction times to initiate movements, EMG patterns, movement kinematics
(position, velocity, acceleration, curvature), eye movement. Actigraphy: We will quantify
continuous recordings of motion sensors involving multiaxial accelerometers and gyroscopes.
Furthermore, we may measure autonomic data during the course of experiments (such as blood
pressure, skin conductance, and respiratory rate) which would correlate to the outcome
measures.
The purpose of this protocol is to study the phenotypic spectrum and the pathophysiology of
tremor syndromes by performing small behavioral, electrophysiological and neuroimaging
sub-studies. The protocol includes techniques with minimal risk (standard clinical
evaluation, MRI, EEG, peripheral nerve stimulation, single and paired pulse TMS) and certain
sub-studies may involve healthy volunteers. This protocol aims to study neurophysiological
and behavioral outcomes in defined groups of patients with action tremor syndromes, to inform
future hypothesis-driven and confirmatory studies, which will be developed and submitted as
separate protocols. For this purpose, we aim to conduct 1) pilot sub-studies, 2) individual
patient investigations, 3) training studies for investigators, as well as 4) technical
development studies.
Study population:
We intend to up to 300 patients with essential tremor and other isolated action tremor
syndromes, as well as 150 healthy volunteers.
Design:
This is a non-hypothesis driven study involving standardized phenotyping as well as thematic
sub-studies. After patients and healthy volunteers complete a screening visit, patients will
undergo a standardized phenotyping visit including clinical rating scales as well as
electrophysiological tremor-workup. Patient and healthy controls may then be enrolled in
sub-studies, which are pertinent to the theme of this protocol. If a sub-study leads to
results of interest, a separate protocol will be submitted with a priori hypotheses, specific
study design and power analysis adapted from the pilot or exploratory sub-studies performed
in the present protocol. At any given time, no more than 5 sub-studies can be actively
accruing subjects concurrently.
Outcome measures:
Outcome measures applied in this protocol involve methods for tremor phenotyping such as
clinical rating scales and questionnaires, electrophysiological tremor studies, videotaped
exam, as well as digitizing based tasks. During the thematic studies focused on the
neurophysiological characterization of tremor syndromes, the following outcome measures will
be applied: EMG: we will analyze tremor signals using spectral analyses, coherence analyses,
and in combination with accelerometry, EEG, MEG, and TMS to explore tremor-networks. MRI: we
will analyze measures such as the amplitude of the BOLD signal (fMRI); tractography between
seed and target regions of interest (using DTI); morphometry of brain regions (using VBM);
and different neurotransmitter levels in brain regions of interest (using MRS). EEG and MEG:
we will quantify measures such as corticomuscular coherence, event- or task-related
potentials, synchronization/desynchronization, and coherence between sensors or sources
located close to the brain areas of interest. TMS: we will analyze measures such as MEP
amplitude and central conduction time, as well as measures of cortical excitability and
inhibition paradigms. Behavioral measures: we will quantify measures of voluntary movement
involving tremor, reaction times to initiate movements, EMG patterns, movement kinematics
(position, velocity, acceleration, curvature), eye movement. Actigraphy: We will quantify
continuous recordings of motion sensors involving multiaxial accelerometers and gyroscopes.
Furthermore, we may measure autonomic data during the course of experiments (such as blood
pressure, skin conductance, and respiratory rate) which would correlate to the outcome
measures.
- INCLUSION CRITERIA FOR TREMOR PATIENTS:
- Patients diagnosed with a tremor syndrome, including, but not limited to
- Essential tremor (per definition of the Tremor Research Group)
- Parkinson disease (per UK Brain Bank criteria)
- Focal tremor such as isolated head tremor, voice tremor
- Task-specific tremor such as primary writing tremor
- Orthostatic tremor
- Patients with other tremor syndromes such as dystonic tremor, intention tremor,
etc.
- Age 18 or older
- Able to give informed consent
- Agree to not drink caffeine or alcohol for 12 hours before phenotyping and selected
thematic study visits because both agents can modify brain activity and may confound
outcome measures.
INCLUSION CRITERIA FOR HEALTHY VOLUNTEERS:
- Age 18 or older.
- Able to give informed consent.
- Agree to not consume caffeine or alcohol for 12 hours before selected thematic study
visits because both agents may modify the activity of the brain during the study.
EXCLUSION CRITERIA FOR TREMOR PATIENTS:
- Problematic alcohol use, as defined by a score of 8 or higher on the WHO Alcohol Use
Disorders Identification Test (AUDIT).
- History of a brain tumor, a stroke, traumatic brain injury, epilepsy or a history of
seizures.
- History of psychotic disorder, Bipolar Disorder or a current depressive episode.
- History or clinical evidence of another neurologic disorder than a tremor syndrome as
defined above, which may interfere with the ability to comply with protocol
requirements or interpret the obtained results.
EXCLUSION CRITERIA FOR HEALTHY VOLUNTEERS:
- Have abnormal findings of clinical significance on the neurological examination that
may affect the scientific integrity of the study
- Problematic alcohol use, as defined by a score of 8 or higher on the WHO Alcohol Use
Disorders Identification Test (AUDIT)
- History of a brain tumor, a stroke, traumatic brain injury, epilepsy or a history of
seizures.
- History of psychotic disorder, Bipolar Disorder or a current depressive episode.
ADDITIONAL EXCLUSION CRITERIA FOR MOVEMENT DISORDER PATIENTS AND HEALTHY VOLUNTEERS
SPECIFICALLY FOR MRI:
We will follow the NMR Center guidelines for MR safety.
Some of the exclusions are:
- Have non-MRI compatible metal in the body, such as a cardiac pacemaker, brain
stimulator, shrapnel, surgical metal, clips in the brain or on blood vessels, cochlear
implants, artificial heart valves or ferromagnetic fragments in the eye or oral cavity
as these make having an MRI unsafe.
- Unable to lie flat on the back for the expected length of the experiment.
- Have uncontrolled movements of the head.
- Have an abnormality on the brain imaging or neurologic examination not related to the
diagnosis.
- Uncomfortable being in a small space for the expected length of the experiment.
- Non-removable body piercing or tattoo posing MRI risk
- Pregnancy.
ADDITIONAL EXCLUSION CRITERIA FOR TREMOR PATIENTS AND HEALTHY VOLUNTEERS FOR TMS AND MRI:
- Ferromagnetic metal in the cranial cavity or eye, e.g. aneurysm clip or ocular foreign
body.
- Implanted electronic device including deep brain stimulation systems.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
301-496-2563
Phone: 800-411-1222
National Institutes of Health Clinical Center The National Institutes of Health (NIH) Clinical Center in...
Click here to add this to my saved trials
