Multiple SclerosisNCT00954421
Use of Two Deep Brain Stimulation (DBS) Electrodes to Treat Post-Traumatic Tremor
A study testing Deep Brain Stimulation in people with Multiple Sclerosis, run by University of Florida at 1 site in United States.
Trial summary
The purpose of this research study is to: 1. Determine whether deep brain stimulation (DBS) with two leads (very thin coiled wires) placed unilaterally (on one side of the brain) is beneficial to patients with multiple sclerosis (MS) tremor. 2. Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Deep Brain Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2006to Dec 2013
- Phase
- Interventional
- 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 18 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The patient must have an unequivocal diagnosis of Multiple Sclerosis (MS) resulting in disabling tremor as indicated by a score of at least 3 on the Tremor Rating Scale (TRS) baseline global assessments by the examiner and the patient.
- The patient must have a history of an unsatisfactory response to medical management. Any patient will need to have tried and failed at least one drug from at least three of the four following medication classes: anticholinergics, muscle relaxants, benzodiazepines, and beta blockers. Alternatively, a patient may also qualify if tremor-suppressing medications are contraindicated due to a coexisting medical condition or drug allergy.
- The MS patient must have disabling and medically refractory unilateral or bilateral upper extremity tremor. Patients with associated ipsilateral lower extremity tremor are not excluded.
- The tremor must meet the following specific diagnostic criteria:
- The tremor must be predominantly postural or action (versus resting) and have a rhythmic and/or ballistic characteristic.
- The tremor may not have features that indicate a significant cerebellar etiology (i.e., non-prominent ataxia, dysdiadokokinesia, dysmetria).
- The tremor must have been present and either stable or progressing for greater than one year.
- The tremor must be disabling. Disabling is defined as significant impairment of the normal functions of daily life as indicated by a score of at least 5 on the Clinical Global Impression (CGI)-Severity scale.
Who cannot join
- Significant medical disease that would excessively increase risk of peri-operative complications (significant cardiac or pulmonary disease, uncontrolled hypertension, inadequately treated major depression).
- More than mild non-tremor cerebellar dysfunction (ataxia, dysmetria, dysdiadokokinesia).
- Evidence of secondary/atypical movement disorder as suggested by presence of the following:
- history of stroke(s)
- exposure to toxins or neuroleptics
- history of encephalitis
Show all 12Show fewer
- neurological signs of upper motor neuron disease, supranuclear gaze palsy, or significant orthostatic hypotension
- MRI with significant evidence of severe brain atrophy or other prohibitive abnormalities (absence of thalamic target for Deep Brain Stimulation (DBS), lacunar infarcts, or iron deposits in the putamen).
- Cognitive dysfunction as evidenced by a score of less than 120 on the Mattis Dementia Rating Scale (MDRS) Such patients will be excluded because significant dementia places the patient at high risk for surgery-induced deterioration of cognitive function, and such patients might have limited ability to accurately assess the impact of DBS.
- Major psychiatric disorder on the Structured Clinical Interview (SCID-IV) for the Diagnostic and Statistical Manual Version 4 (DSM-IV). 45 Patients with Major Depression within 3 months of entry into the study will be excluded. High rates of psychiatric co-morbidity can complicate any neurosurgical study. While the cleanest study would exclude patients with psycho-pathology, we do not believe this is realistic or practical, given the majority of patients with advanced movement disorders will suffer from some degree of anxiety or depression. We will screen patients for psychiatric disorders, treat disorders prior to DBS and admit patients who are psychiatrically stable for at least 3 months prior to entry (without active psychiatric diagnosis by SCID criteria).
- Patients with any implanted device that precludes magnetic resonance imaging (MRI) will be excluded from this study. Examples of such devices include cochlear implants, spinal cord stimulators, many cardiac pacemakers, and some older aneurysm clips
- Patients who have a known need for future MRIs or diathermy treatments will be excluded from this study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Use of Two DBS Electrodes to Treat Post-Traumatic Tremor
The purpose of this research study is to:
- Determine whether deep brain stimulation (DBS) with two leads (very thin coiled wires) placed unilaterally (on one side of the brain) is beneficial to patients with multiple sclerosis (MS) tremor.
- Compare the two different locations of the DBS lead placement in effectiveness for treatment of muscle tremors that do not respond to treatment with medication caused by multiple sclerosis.
- Evaluate any side effects that may result from the two DBS leads.
Read the detailed description
Surgical treatment of disabling multiple sclerosis (MS) tremor that does not respond to medication has proven difficult. To date, there have been no prospective blinded studies to evaluate efficacy of surgical treatments for these tremors. Based on prior data, this study will examine the use of 2 DBS electrodes on the same side of the brain in the thalamus region (one at an area referred to as the "ventralis intermedius nucleus/ventralis oralis posterior nucleus border," or "VIM," and one at a region called the "ventralis oralis anterior nucleus/ventralis oralis posterior nucleus border," or "VO") for treatment of MS tremor. This study will test the effectiveness of VIM combined with, and independent of, VO DBS, and characterize safety, benefits and side effects of this procedure for treatment of MS-related tremors.
- Conditions
- Multiple Sclerosis
- Being tested
- Deep Brain Stimulation
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Deep Brain StimulationDevice
Use of two ipsilateral thalamic Deep Brain Stimulation electrodes (one at the ventralis intermedius nucleus/ventralis oralis posterior nucleus border or VIM and one at the ventralis oralis anterior nucleus/ventralis oralis posterior nucleus border or VO) for treatment of disabling and medication refractory tremor secondary to head trauma or multiple sclerosis.
| Study group | Role | What they receive |
|---|---|---|
| Deep Brain Stimulation | Experimental | Multiple Sclerosis Tremor treated with VIM and VO Deep Brain Stimulation Receives: Device: Deep Brain Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fain-Tolosa-Marin Tremor Rating Scale (TRS) Change Score for Both VIM and VO ON (Baseline Minus 6 Months Post-implant)
Tremor was evaluated using the Fain-Tolosa-Marin Tremor Rating Scale (TRS). Score was obtained by summing all 21 items, each of which assessed tremor on a scale of 0-4. Because some of the 21 items contained more than one subsection, total maximum score was 144, and minimum score was 0. Higher scores represent worse tremor.
Both VIM and VO stimulators will be turned ON and TRS score at 6 months will be compared to pre-implant (baseline).
Measured: Change from Baseline to Six Months
Secondary outcomes (1)
Fain-Tolosa-Marin Tremor Rating Scale (TRS) Change Score for Either VIM or VO On, and for Both VIM and VO Off (Baseline Minus 6 Months Post-implant)
Tremor was evaluated using the Fain-Tolosa-Marin Tremor Rating Scale (TRS). Score was obtained by summing all 21 items, each of which assessed tremor on a scale of 0-4. Because some of the 21 items contained more than one subsection, total maximum score was 144, and minimum score was 0. Higher scores represent worse tremor.
Both VIM and VO stimulators will be turned ON and TRS score at 6 months will be compared to pre-implant (baseline).
Either VO or VIM stimulator will be turned on (as opposed to both stimulators, as in outcome measure 1), and change in Tremor Rating Scale scores will be compared. The effects of each individual stimulator will also be compared to both being turned on.
Measured: Baseline to Six Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2009 (estimated)
- Study startNov 2006
- Primary completionJun 2012
- Study completionDec 2013
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by University of FloridaThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kelly Foote, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00954421
- Sponsor's protocol ID
- 461-2006
- Other IDs
- K23NS052557
- Status last verified
- Jul 2014
- First submitted
- 27 Jul 2009
- Last updated
- 25 Jul 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Oliveria SF, Rodriguez RL, Bowers D, Kantor D, Hilliard JD, Monari EH, Scott BM, Okun MS, Foote KD. Safety and efficacy of dual-lead thalamic deep brain stimulation for patients with treatment-refractory multiple sclerosis tremor: a single-centre, randomised, single-blind, pilot trial. Lancet Neurol. 2017 Sep;16(9):691-700. doi: 10.1016/S1474-4422(17)30166-7. Epub 2017 Jun 20.
PubMed 28642125
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Two DBS Electrodes to Treat Post-Traumatic Tremor
- ClinicalTrials.gov ID
- NCT00954421
- Acronym / sponsor ID
- 461-2006
- Conditions
- Multiple Sclerosis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), Medtronic
- Study start
- Nov 2006
- Primary completion
- Jun 2012 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 7 Aug 2009 (estimated)
- Results
- Posted 27 Jun 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to:
- Determine whether deep brain stimulation (DBS) with two leads (very thin coiled wires) placed unilaterally (on one side of the brain) is beneficial to patients with multiple sclerosis (MS) tremor.
- Compare the two different locations of the DBS lead placement in effectiveness for treatment of muscle tremors that do not respond to treatment with medication caused by multiple sclerosis.
- Evaluate any side effects that may result from the two DBS leads.
Detailed description
Surgical treatment of disabling multiple sclerosis (MS) tremor that does not respond to medication has proven difficult. To date, there have been no prospective blinded studies to evaluate efficacy of surgical treatments for these tremors. Based on prior data, this study will examine the use of 2 DBS electrodes on the same side of the brain in the thalamus region (one at an area referred to as the "ventralis intermedius nucleus/ventralis oralis posterior nucleus border," or "VIM," and one at a region called the "ventralis oralis anterior nucleus/ventralis oralis posterior nucleus border," or "VO") for treatment of MS tremor. This study will test the effectiveness of VIM combined with, and independent of, VO DBS, and characterize safety, benefits and side effects of this procedure for treatment of MS-related tremors.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Deep Brain Stimulation | Experimental | Device: Deep Brain StimulationMultiple Sclerosis Tremor treated with VIM and VO Deep Brain Stimulation |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- The patient must have an unequivocal diagnosis of Multiple Sclerosis (MS) resulting in disabling tremor as indicated by a score of at least 3 on the Tremor Rating Scale (TRS) baseline global assessments by the examiner and the patient.
- The patient must have a history of an unsatisfactory response to medical management. Any patient will need to have tried and failed at least one drug from at least three of the four following medication classes: anticholinergics, muscle relaxants, benzodiazepines, and beta blockers. Alternatively, a patient may also qualify if tremor-suppressing medications are contraindicated due to a coexisting medical condition or drug allergy.
- The MS patient must have disabling and medically refractory unilateral or bilateral upper extremity tremor. Patients with associated ipsilateral lower extremity tremor are not excluded.
- The tremor must meet the following specific diagnostic criteria:
Key exclusion criteria (12 listed)
- Significant medical disease that would excessively increase risk of peri-operative complications (significant cardiac or pulmonary disease, uncontrolled hypertension, inadequately treated major depression).
- More than mild non-tremor cerebellar dysfunction (ataxia, dysmetria, dysdiadokokinesia).
- Evidence of secondary/atypical movement disorder as suggested by presence of the following:
- MRI with significant evidence of severe brain atrophy or other prohibitive abnormalities (absence of thalamic target for Deep Brain Stimulation (DBS), lacunar infarcts, or iron deposits in the putamen).
- Cognitive dysfunction as evidenced by a score of less than 120 on the Mattis Dementia Rating Scale (MDRS) Such patients will be excluded because significant dementia places the patient at high risk for surgery-induced deterioration of cognitive function, and such patients might have limited ability to accurately assess the impact of DBS.
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 |
|---|---|---|
| Deep Brain StimulationUse of two ipsilateral thalamic Deep Brain Stimulation electrodes (one at the ventralis intermedius nucleus/ventralis oralis posterior nucleus border or VIM and one at the ventralis oralis anterior nucleus/ventralis oralis posterior nucleus border or VO) for treatment of disabling and medication refractory tremor secondary to head trauma or multiple sclerosis. | Device | Deep Brain Stimulation |
Primary outcome
Fain-Tolosa-Marin Tremor Rating Scale (TRS) Change Score for Both VIM and VO ON (Baseline Minus 6 Months Post-implant)
Time frame: Change from Baseline to Six Months
Tremor was evaluated using the Fain-Tolosa-Marin Tremor Rating Scale (TRS). Score was obtained by summing all 21 items, each of which assessed tremor on a scale of 0-4. Because some of the 21 items contained more than one subsection, total maximum score was 144, and minimum score was 0. Higher scores represent worse tremor. Both VIM and VO stimulators will be turned ON and TRS score at 6 months will be compared to pre-implant (baseline).
1 secondary outcome
Fain-Tolosa-Marin Tremor Rating Scale (TRS) Change Score for Either VIM or VO On, and for Both VIM and VO Off (Baseline Minus 6 Months Post-implant)
Time frame: Baseline to Six Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28642125Oliveria SF, Rodriguez RL, Bowers D, Kantor D, Hilliard JD, Monari EH, Scott BM, Okun MS, Foote KD. Safety and efficacy of dual-lead thalamic deep brain stimulation for patients with treatment-refractory multiple sclerosis tremor: a single-centre, randomised, single-blind, pilot trial. Lancet Neurol. 2017 Sep;16(9):691-700. doi: 10.1016/S1474-4422(17)30166-7. Epub 2017 Jun 20.
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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.
Kelly Foote, MD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Deep Brain Stimulation in people with Multiple Sclerosis, run by University of Florida 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 8 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 25 Jul 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 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?
Yes. Results are posted in the registry (first posted 27 Jun 2014). 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?
Fain-Tolosa-Marin Tremor Rating Scale (TRS) Change Score for Both VIM and VO ON (Baseline Minus 6 Months Post-implant) (time frame: Change from Baseline to Six Months). 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 NCT00954421, which also lists 1 linked publication.
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 25 Jul 2014.