Essential TremorPhase 1NCT01698450
Magnetic Resonance (MR) Guided Functional Ultrasound-Neurosurgery for Movement Disorders
A Phase 1 study testing Non-invasive intervention with focused ultrasound (ExAblate 4000) in people with Essential Tremor and Dystonia, run by University Children's Hospital, Zurich at 1 site in Switzerland.
Trial summary
The aim of this study is to asses the efficacy and the clinical safety of the transcranial magnetic resonance guided high intensity focused ultrasound system ExAblate 4000, InSightec Ltd. for functional neurosurgery in the treatment of movement disorders. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Essential Tremor, Dystonia, Parkinson's Disease
- What is being tested?
- Non-invasive intervention with focused ultrasound (ExAblate 4000)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteSwitzerland
- Study dates
- Nov 2012to Dec 2013
- Phase
- Phase 1
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women, between 18 and 80 years, inclusive.
- Patients who are able and willing to give consent and able to attend all study visits.
- A diagnosis of a MD, such as Essential Tremor (ET), Idiopathic Parkinson's diseases or primary Dystonia as confirmed from clinical history and examination by a movement disorder neurologist.
- A MD refractory to adequate medical treatment, or in whom the indication for Deep Brain Stimulation (DBS) would be given, but DBS cannot be performed because of medical comorbidities or medical reasons, or because the patient clearly confirms by written statement that he does not want to undergo DBS for personal reasons (PD: increasing motor fluctuations albeit optimal medical treatment \& unbearable side effects of medication; ET: failure of adequate tremor control with Propranolol and Primidone alone and in combination; Dystonia: dystonia or pain not controlled by oral medication). An adequate medication trial is defined as a therapeutic dose of each medication or the development of side effects as the medication dose is titrated.
- Either the medial thalamic nuclei or the subthalamic or pallidal areas can be target by the ExAblate device. The target region must be apparent on MRI such that targeting can be performed with either direct visualization or by measurement from landmarks, using the "Stereotactic Atlas of the Human Thalamus and Basal Ganglia" by Anne Morel, 39 analogous to our first clinical FUS study on patients with chronic pain 33.
- Able to communicate sensations during the ExAblate MRgFUS treatment
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- Stable doses of all medications for 30 days prior to study entry and for the duration of the study.
- Significant disability due to MD despite medical treatment (speaking, feeding other than liquids, bringing liquids to mouth, hygiene, dressing, writing, working, and social activities)
- Inclusion and exclusion criteria have been agreed upon by two members of the medical team.
Who cannot join
- Patients with unstable cardiac status including:
- Unstable angina pectoris on medication
- Patients with documented myocardial infarction within six months of protocol entry
- Congestive heart failure requiring medication (other than diuretic)
- Patients on anti-arrhythmic drugs
- Patients exhibiting any behavior(s) consistent with ethanol or substance abuse as defined by the criteria outlined in the DSM-IV as manifested by one (or more) of the following occurring within a 12 month period:
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- Recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home (such as repeated absences or poor work performance related to substance use; substance-related absences, suspensions, or expulsions from school; or neglect of children or household).
- Recurrent substance use in situations in which it is physically hazardous (such as driving an automobile or operating a machine when impaired by substance use)
- Recurrent substance-related legal problems (such as arrests for substance related disorderly conduct)
- Continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance (for example, arguments with spouse about consequences of intoxication and physical fights).
- Severe hypertension (diastolic BP > 100 on medication)
- Patients with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc.
- Known intolerance or allergies to the MRI contrast agent (e.g. Gadolinium) including advanced kidney disease
- Severely impaired renal function (estimated glomerular filtration rate < 45ml/min/ 1.73 m2) or receiving dialysis
- History of abnormal bleeding and/or coagulopathy
- Receiving anticoagulant (e.g. warfarin) or antiplatelet (e.g. aspirin) therapy within one week of focused ultrasound procedure or drugs known to increase risk or hemorrhage (e.g. Avastin) within one month of focused ultrasound procedure
- Active or suspected acute or chronic uncontrolled infection
- History of intracranial hemorrhage
- Cerebrovascular disease (multiple CVA or CVA within 6 months)
- Individuals who are not able or willing to tolerate the required prolonged stationary supine position during treatment (can be up to 4 hrs of total table time.)
- Symptoms and signs of increased intracranial pressure (e.g. headache, nausea, vomiting, lethargy, and papilledema)
- Participation in another clinical trial in the last 30 days
- Patients unable to communicate with the investigator and staff.
- Presence of any other neurodegenerative disease like Parkinson-plus syndromes suspected on neurological examination. These include: multisystem atrophy, progressive supranuclear palsy, dementia with Lewy bodies, and Alzheimer's disease.
- Presence of significant cognitive impairment as determined with a score ≤ 24 on the Mini Mental Status Examination (MMSE)
- Compromised Immune System, including HIV positive serum status
- Known life-threatening systemic disease
- Patients with a history of seizures within the past year
- Patients with current or a prior history of any psychiatric illness will be excluded. Any presence or history of psychosis will be excluded. Patients with a significant mood disorders including depression will be excluded. For the purpose of this study, we consider a significant mood disorder to include any patient who has:
- been under the care of a psychiatrist for over 3 months
- taken antidepressant medications for greater than 6 months
- has participated in cognitive-behavioral therapy
- been hospitalized for the treatment of a psychiatric illness
- received transcranial magnetic stimulation
- received electroconvulsive therapy
- Patients with risk factors for intraoperative or postoperative bleeding (platelet count less than 100,000 per cubic millimeter, PT > 14, PTT > 36 or INR > 1.3) or a documented coagulopathy
- Patients with brain tumors
- Any illness that in the investigator's opinion preclude participation in this study.
- Pregnancy or lactation.
- Legal incapacity or limited legal capacity.
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
MR-Center, University Children's Hospital
Zurich, Canton of Zurich
About this study
Official title: MR-Guided Functional Ultrasound-Neurosurgery for Movement Disorders
The aim of this study is to asses the efficacy and the clinical safety of the transcranial magnetic resonance guided high intensity focused ultrasound system ExAblate 4000, InSightec Ltd. for functional neurosurgery in the treatment of movement disorders. The treatments to be conducted in this study are non-invasive, i.e. without opening the skull, and will create microthalamotomies in specific target areas such as thalamus, subthalamus and pallidum. The data obtained in this study will be used to evaluate the basic safety aspects of this new treatment technology and will serve as a basis for the clinical introduction of MR-guided ultrasound neurosurgery.
- Conditions
- Essential Tremor, Dystonia, Parkinson's Disease
- Being tested
- Non-invasive intervention with focused ultrasound (ExAblate 4000)
- Keywords
- FUS, focused ultrasound, functional brain disorder, neuropathic pain, movement disorders, malignant brain tumors
- Medical subject headings
- Essential Tremor, Dystonia, Parkinson Disease, Neuralgia, Movement Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Non-invasive intervention with focused ultrasound (ExAblate 4000)Device
Also called ExAblate 4000
Non-invasive brain intervention using MR-guided focused ultrasound
| Study group | Role | What they receive |
|---|---|---|
| Focused Ultrasound for Movement Disorders | Other | Not described Receives: Device: Non-invasive intervention with focused ultrasound (ExAblate 4000) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lesion Size
Size of lesion in the target area for each sonication as a function of applied energy/temperature.
Measured: 3 months
Patient Safety
Number of Patients with Adverse Events as a Measure of Safety and Tolerability.
Measured: 3 months
Secondary outcomes (1)
Clinical efficacy and QOL
Efficacy and QOL will be quantified on respective rating scales (specified in protocol).
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2012 (estimated)
- Study startNov 2012
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Essential TremorStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Children's Hospital, Zurich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ernst - Martin, MD, Principal investigator, University Children's Hospital, ZurichRonald - Bauer, MD, Principal investigator, Neurosurgey, Kantonsspital St. Gallen, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01698450
- Sponsor's protocol ID
- EK: 2012-0027
- Status last verified
- Oct 2014
- First submitted
- 2 Jul 2012
- Last updated
- 9 Oct 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MR-Guided Functional Ultrasound-Neurosurgery for Movement Disorders
- ClinicalTrials.gov ID
- NCT01698450
- Acronym / sponsor ID
- EK: 2012-0027
- Conditions
- Essential Tremor, Dystonia, Parkinson's Disease
- Keywords
- FUS, focused ultrasound, functional brain disorder, neuropathic pain, movement disorders, malignant brain tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University Children's Hospital, ZurichUniversity, hospital or other
- Study start
- Nov 2012
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 3 Oct 2012 (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.
The aim of this study is to asses the efficacy and the clinical safety of the transcranial magnetic resonance guided high intensity focused ultrasound system ExAblate 4000, InSightec Ltd. for functional neurosurgery in the treatment of movement disorders. The treatments to be conducted in this study are non-invasive, i.e. without opening the skull, and will create microthalamotomies in specific target areas such as thalamus, subthalamus and pallidum. The data obtained in this study will be used to evaluate the basic safety aspects of this new treatment technology and will serve as a basis for the clinical introduction of MR-guided ultrasound neurosurgery.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Focused Ultrasound for Movement Disorders | Other | Device: Non-invasive intervention with focused ultrasound (ExAblate 4000) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Men and women, between 18 and 80 years, inclusive.
- Patients who are able and willing to give consent and able to attend all study visits.
- A diagnosis of a MD, such as Essential Tremor (ET), Idiopathic Parkinson's diseases or primary Dystonia as confirmed from clinical history and examination by a movement disorder neurologist.
- A MD refractory to adequate medical treatment, or in whom the indication for Deep Brain Stimulation (DBS) would be given, but DBS cannot be performed because of medical comorbidities or medical reasons, or because the patient clearly confirms by written statement that he does not want to undergo DBS for personal reasons (PD: increasing motor fluctuations albeit optimal medical treatment \& unbearable side effects of medication; ET: failure of adequate tremor control with Propranolol and Primidone alone and in combination; Dystonia: dystonia or pain not controlled by oral medication). An adequate medication trial is defined as a therapeutic dose of each medication or the development of side effects as the medication dose is titrated.
- Either the medial thalamic nuclei or the subthalamic or pallidal areas can be target by the ExAblate device. The target region must be apparent on MRI such that targeting can be performed with either direct visualization or by measurement from landmarks, using the "Stereotactic Atlas of the Human Thalamus and Basal Ganglia" by Anne Morel, 39 analogous to our first clinical FUS study on patients with chronic pain 33.
Key exclusion criteria (40 listed)
- Patients with unstable cardiac status including:
- Patients exhibiting any behavior(s) consistent with ethanol or substance abuse as defined by the criteria outlined in the DSM-IV as manifested by one (or more) of the following occurring within a 12 month period:
- Severe hypertension (diastolic BP > 100 on medication)
- Patients with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc.
- Known intolerance or allergies to the MRI contrast agent (e.g. Gadolinium) including advanced kidney disease
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 |
|---|---|---|
| Non-invasive intervention with focused ultrasound (ExAblate 4000)Also: ExAblate 4000Non-invasive brain intervention using MR-guided focused ultrasound | Device | Focused Ultrasound for Movement Disorders |
Primary outcome
Lesion Size
Time frame: 3 months
Size of lesion in the target area for each sonication as a function of applied energy/temperature.
Patient Safety
Time frame: 3 months
Number of Patients with Adverse Events as a Measure of Safety and Tolerability.
1 secondary outcome
Clinical efficacy and QOL
Time frame: 3 months
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 9 Oct 2014.
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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.
Ernst - Martin, MD principal investigator
University Children's Hospital, Zurich
Ronald - Bauer, MD principal investigator
Neurosurgey, Kantonsspital St. Gallen, Switzerland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Non-invasive intervention with focused ultrasound (ExAblate 4000) in people with Essential Tremor and Dystonia, run by University Children's Hospital, Zurich at 1 site in Switzerland.
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 9 inclusion and 40 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 9 Oct 2014. 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 Switzerland. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Lesion Size (time frame: 3 months). 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?
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 9 Oct 2014.