DystoniaNCT02468843
Novel Stimulation Patterns for the Treatment of Dystonia
An observational study of Dystonia and Cervical Dystonia, run by University of Florida at 1 site in United States.
Trial summary
Deep brain stimulation (DBS) is an effective surgical therapy for select Dystonia patients who are refractory to medications or who have generalized symptoms (e.g. patients with Early-Onset Primary Dystonia(DYT1) mutations and other dystonia subtypes). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Dystonia, Cervical Dystonia
- What is being tested?
- Biphasic DBS stimulation, Unified Dystonia Rating Scale and Burke-Fahn- Marsden scale
- Type of treatment
- Medical device
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2015to Aug 2016
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: This is a preliminary pilot investigation that will utilize a within subjects study design and will screen 10 generalized dystonia and screen 10 cervical dystonia patients.
Who may be able to join
- Diagnosis of primary generalized dystonia or cervical dystonia
- Bilaterally implanted globus pallidus interus(GPi) DBS.
- Minimum of 6 months of chronic stimulation
- Greater than 60 days on stable DBS settings
Who cannot join
- Does not have DBS for dystonia or cervical dystonia
Trial locations and contacts
1 site in 1 country.
United States1 site
Center for Movement Disorders and Neurorestoration
Gainesville, Florida, 32607
About this study
Official title: Novel Stimulation Patterns and Personalized Deep Brain Stimulation for the Treatment of Dystonia
Deep brain stimulation (DBS) is an effective surgical therapy for select Dystonia patients who are refractory to medications or who have generalized symptoms (e.g. patients with Early-Onset Primary Dystonia(DYT1) mutations and other dystonia subtypes). DBS patients typically experience significant improvement in disabling symptoms; however, detailed programming is always required, and stimulation-induced side effects commonly emerge. Clinicians may empirically vary voltage, pulse width, frequency and also the active contacts on the DBS lead to achieve observed optimal benefits.
The majority of DBS patients undergo repeat surgeries to replace the implantable pulse generator (IPG) every 2.5 to 5 years. It has been demonstrated that, in dystonia patients, that higher settings are required for adequate symptomatic control, and that neurostimulators have a considerably shorter life when compared to neurostimulators from patients with essential tremor or Parkinson's disease. Additionally, several smaller studies have suggested that alternative pulse stimulation properties and pulse shape modifications can lower IPG battery consumption.
Read more
Newer patterns of stimulation (regularity of pulses and shapes of pulses) have not been widely tested in clinical practice, and are not part of the current FDA device labeling. Novel patterns of stimulation do however, have the potential to improve symptoms, reduce side effects, and to preserve the neurostimulator life.
The current research proposal will prospectively study biphasic pulse stimulation paradigms and its effects on dystonic symptoms. The investigators aim to demonstrate that we can tailor DBS settings to address dystonia symptoms, improve the safety profile, characterize distinct clinical advantages, and carefully document the safety and neurostimulator battery consumption profile for biphasic stimulation.
Read the detailed description
In this research study, different stimulation patterns on the DBS device will be tried for effectiveness against current symptoms. There will be two different stimulation patterns that will be performed and can occur at different clinic dates. Each of the stimulation patterns will have times varying between 2-3 hours per stage. One part of the study will deliver stimulation in a continuous manner, while the other part of the study will deliver stimulation based upon responses obtained from changes in brain wave patterns. These procedures can be performed while in the clinic for regular programming visits or at different visits. The current DBS setting will be recorded and at the end of the session the setting will be reset to back to the previous settings. The participant will have the option of participating in both or just one part.
During the visit, the participant will be analyzed for tremor and slowness by using the Trigno wireless Electromyography (EMG) and the Kinesia system. The system includes a unit composed of two modules: a wrist module, which is the size of an I-Pod and will be attached to the wrist over a comfortable wristband, and a sensor module, which will be placed over the index finger.
The entire visit will be videotaped and UDRS (Unified Dystonia Disease Rating Scale) and BFMDRS (Burke-Fahn-Marsden Dystonia Rating Scale) scores will be evaluated by two scorers. Pre-DBS "off" and "on" scores will also be taken.
- Conditions
- Dystonia, Cervical Dystonia
- Being tested
- Biphasic DBS stimulation, Unified Dystonia Rating Scale, Burke-Fahn- Marsden scale
- Keywords
- Deep brain stimulation, DBS, Dystonia, DYT1
- Medical subject headings
- Dystonia, Torticollis, Dystonia musculorum deformans type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biphasic DBS stimulationDevice
The following protocol will be followed for each subject. In between, baseline and novel stimulation settings there will be a 30-minute washout period with DBS in the off state.
- Current best/optimized DBS setting (considered "baseline")
- DBS off for 30 minutes
- Biphasic pulse stimulation mode (immediate assessment)
- Biphasic pulse stimulation mode (assessment at 1h)
- Biphasic pulse stimulation mode (assessment at 2h)
Unified Dystonia Rating ScaleOther
Also called UDRS
Neurologist use the UDRS to determine the severity and duration of dystonia on 14 body areas.
Burke-Fahn- Marsden scaleOther
Also called BFMDRS
Neurologist use the BFMDRS to rate the severity of dystonia in 9 regions of the body.
| Study group | Role | What they receive |
|---|---|---|
| Biphasic DBS stimulations | Subjects in this group with have Biphasic DBS stimulation setting performed, Unified Dystonia Rating Scale (UDRS), and Burke-Fahn- Marsden scale (BFMDRS), tremor accelerometer, kinesia accelerometer, and GaitRite walking assessments performed. Receives: Device: Biphasic DBS stimulation; Other: Unified Dystonia Rating Scale; Other: Burke-Fahn- Marsden scale |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blinded Unified Dystonia Rating Scale (UDRS)
Neurologist use the UDRS to determine the severity and duration of dystonia on 14 body areas. Each body region is assessed and scores range from 0 (no dystonia) to 4 (extreme dystonia). The maximum UDRS score is 112 and includes severity and duration factors.
Measured: Day 1
Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS)
Neurologist use the BFMDRS to rate the severity of dystonia in 9 regions of the body. Provoking and severity factors are ranked from 0 (no dystonia) to 4 (extreme dystonia) for each body region and then adjusted scores are summed to give an overall score from 0 to 120.
Measured: Day 1
Secondary outcomes (4)
Tremor accelerometer to measure motor dysfunction
Tremor accelerometer for the patients with a component of dystonic tremor (device taped or attached to the wrist by an elastic band to record how fast the tremor).
Measured: Day 1
Kinesia accelerometer to measure motor dysfunction
Kinesia accelerometer for the patients with a mobile component of dystonia (device attached to the arms and legs (by an elastic band or tape) to record movements).
Measured: Day 1
Battery Consumption compared between pre and post settings
Battery consumption will be calculated and compared between the NEW settings and patients' baseline settings. The Medtronic battery estimator helpline will be used to calculate battery life, as well as the University of Florida calculator.
Measured: Day 2
GaitRite walking assessment.
The GaitRite is an automated floor that when you walk on the floor it records your gait pattern.
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2015 (estimated)
- Study startJul 2015
- Primary completionJan 2016
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for DystoniaStudies 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Medtronic
- Responsible party
- Sponsor
- Investigators
- Leonardo Almeida, MD, Principal investigator, University of Florida Center for Movement Disorders and Neurorestoration
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02468843
- Sponsor's protocol ID
- IRB201500366
- Status last verified
- Oct 2016
- First submitted
- 3 Jun 2015
- Last updated
- 27 Oct 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes
Publications
Fakhar K, Hastings E, Butson CR, Foote KD, Zeilman P, Okun MS. Management of deep brain stimulator battery failure: battery estimators, charge density, and importance of clinical symptoms. PLoS One. 2013;8(3):e58665. doi: 10.1371/journal.pone.0058665. Epub 2013 Mar 11.
PubMed 23536810Rawal PV, Almeida L, Smelser LB, Huang H, Guthrie BL, Walker HC. Shorter pulse generator longevity and more frequent stimulator adjustments with pallidal DBS for dystonia versus other movement disorders. Brain Stimul. 2014 May-Jun;7(3):345-9. doi: 10.1016/j.brs.2014.01.008. Epub 2014 Jan 18.
PubMed 24548586Foutz TJ, McIntyre CC. Evaluation of novel stimulus waveforms for deep brain stimulation. J Neural Eng. 2010 Dec;7(6):066008. doi: 10.1088/1741-2560/7/6/066008. Epub 2010 Nov 17.
PubMed 21084732Hofmann L, Ebert M, Tass PA, Hauptmann C. Modified pulse shapes for effective neural stimulation. Front Neuroeng. 2011 Sep 28;4:9. doi: 10.3389/fneng.2011.00009. eCollection 2011.
PubMed 22007167Brocker DT, Grill WM. Principles of electrical stimulation of neural tissue. Handb Clin Neurol. 2013;116:3-18. doi: 10.1016/B978-0-444-53497-2.00001-2.
PubMed 24112880Birdno MJ, Kuncel AM, Dorval AD, Turner DA, Gross RE, Grill WM. Stimulus features underlying reduced tremor suppression with temporally patterned deep brain stimulation. J Neurophysiol. 2012 Jan;107(1):364-83. doi: 10.1152/jn.00906.2010. Epub 2011 Oct 12.
PubMed 21994263Swan BD, Grill WM, Turner DA. Investigation of deep brain stimulation mechanisms during implantable pulse generator replacement surgery. Neuromodulation. 2014 Jul;17(5):419-24; discussion 424. doi: 10.1111/ner.12123. Epub 2013 Oct 7.
PubMed 24118257Beuter A, Lefaucheur JP, Modolo J. Closed-loop cortical neuromodulation in Parkinson's disease: An alternative to deep brain stimulation? Clin Neurophysiol. 2014 May;125(5):874-85. doi: 10.1016/j.clinph.2014.01.006. Epub 2014 Jan 18.
PubMed 24555921Okun MS, Foote KD, Wu SS, Ward HE, Bowers D, Rodriguez RL, Malaty IA, Goodman WK, Gilbert DM, Walker HC, Mink JW, Merritt S, Morishita T, Sanchez JC. A trial of scheduled deep brain stimulation for Tourette syndrome: moving away from continuous deep brain stimulation paradigms. JAMA Neurol. 2013 Jan;70(1):85-94. doi: 10.1001/jamaneurol.2013.580.
PubMed 23044532
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Stimulation Patterns and Personalized Deep Brain Stimulation for the Treatment of Dystonia
- ClinicalTrials.gov ID
- NCT02468843
- Acronym / sponsor ID
- IRB201500366
- Conditions
- Dystonia, Cervical Dystonia
- Keywords
- Deep brain stimulation, DBS, Dystonia, DYT1
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- Medtronic
- Study start
- Jul 2015
- Primary completion
- Jan 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 11 Jun 2015 (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.
Deep brain stimulation (DBS) is an effective surgical therapy for select Dystonia patients who are refractory to medications or who have generalized symptoms (e.g. patients with Early-Onset Primary Dystonia(DYT1) mutations and other dystonia subtypes). DBS patients typically experience significant improvement in disabling symptoms; however, detailed programming is always required, and stimulation-induced side effects commonly emerge. Clinicians may empirically vary voltage, pulse width, frequency and also the active contacts on the DBS lead to achieve observed optimal benefits.
The majority of DBS patients undergo repeat surgeries to replace the implantable pulse generator (IPG) every 2.5 to 5 years. It has been demonstrated that, in dystonia patients, that higher settings are required for adequate symptomatic control, and that neurostimulators have a considerably shorter life when compared to neurostimulators from patients with essential tremor or Parkinson's disease. Additionally, several smaller studies have suggested that alternative pulse stimulation properties and pulse shape modifications can lower IPG battery consumption.
Newer patterns of stimulation (regularity of pulses and shapes of pulses) have not been widely tested in clinical practice, and are not part of the current FDA device labeling. Novel patterns of stimulation do however, have the potential to improve symptoms, reduce side effects, and to preserve the neurostimulator life.
The current research proposal will prospectively study biphasic pulse stimulation paradigms and its effects on dystonic symptoms. The investigators aim to demonstrate that we can tailor DBS settings to address dystonia symptoms, improve the safety profile, characterize distinct clinical advantages, and carefully document the safety and neurostimulator battery consumption profile for biphasic stimulation.
Detailed description
In this research study, different stimulation patterns on the DBS device will be tried for effectiveness against current symptoms. There will be two different stimulation patterns that will be performed and can occur at different clinic dates. Each of the stimulation patterns will have times varying between 2-3 hours per stage. One part of the study will deliver stimulation in a continuous manner, while the other part of the study will deliver stimulation based upon responses obtained from changes in brain wave patterns. These procedures can be performed while in the clinic for regular programming visits or at different visits. The current DBS setting will be recorded and at the end of the session the setting will be reset to back to the previous settings. The participant will have the option of participating in both or just one part.
During the visit, the participant will be analyzed for tremor and slowness by using the Trigno wireless Electromyography (EMG) and the Kinesia system. The system includes a unit composed of two modules: a wrist module, which is the size of an I-Pod and will be attached to the wrist over a comfortable wristband, and a sensor module, which will be placed over the index finger.
The entire visit will be videotaped and UDRS (Unified Dystonia Disease Rating Scale) and BFMDRS (Burke-Fahn-Marsden Dystonia Rating Scale) scores will be evaluated by two scorers. Pre-DBS "off" and "on" scores will also be taken.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Biphasic DBS stimulations | – | Device: Biphasic DBS stimulation, Other: Unified Dystonia Rating Scale, Other: Burke-Fahn- Marsden scaleSubjects in this group with have Biphasic DBS stimulation setting performed, Unified Dystonia Rating Scale (UDRS), and Burke-Fahn- Marsden scale (BFMDRS), tremor accelerometer, kinesia accelerometer, and GaitRite walking assessments performed. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- This is a preliminary pilot investigation that will utilize a within subjects study design and will screen 10 generalized dystonia and screen 10 cervical dystonia patients.
Key inclusion criteria (4 listed)
- Diagnosis of primary generalized dystonia or cervical dystonia
- Bilaterally implanted globus pallidus interus(GPi) DBS.
- Minimum of 6 months of chronic stimulation
- Greater than 60 days on stable DBS settings
Key exclusion criteria (1 listed)
- Does not have DBS for dystonia or cervical dystonia
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 |
|---|---|---|
| Biphasic DBS stimulationThe following protocol will be followed for each subject. In between, baseline and novel stimulation settings there will be a 30-minute washout period with DBS in the off state. 1. Current best/optimized DBS setting (considered "baseline") 2. DBS off for 30 minutes 3. Biphasic pulse stimulation mode (immediate assessment) 4. Biphasic pulse stimulation mode (assessment at 1h) 5. Biphasic pulse stimulation mode (assessment at 2h) | Device | Biphasic DBS stimulations |
| Unified Dystonia Rating ScaleAlso: UDRSNeurologist use the UDRS to determine the severity and duration of dystonia on 14 body areas. | Other | Biphasic DBS stimulations |
| Burke-Fahn- Marsden scaleAlso: BFMDRSNeurologist use the BFMDRS to rate the severity of dystonia in 9 regions of the body. | Other | Biphasic DBS stimulations |
Primary outcome
Blinded Unified Dystonia Rating Scale (UDRS)
Time frame: Day 1
Neurologist use the UDRS to determine the severity and duration of dystonia on 14 body areas. Each body region is assessed and scores range from 0 (no dystonia) to 4 (extreme dystonia). The maximum UDRS score is 112 and includes severity and duration factors.
Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS)
Time frame: Day 1
Neurologist use the BFMDRS to rate the severity of dystonia in 9 regions of the body. Provoking and severity factors are ranked from 0 (no dystonia) to 4 (extreme dystonia) for each body region and then adjusted scores are summed to give an overall score from 0 to 120.
4 secondary outcomes
Tremor accelerometer to measure motor dysfunction
Time frame: Day 1
Kinesia accelerometer to measure motor dysfunction
Time frame: Day 1
Battery Consumption compared between pre and post settings
Time frame: Day 2
GaitRite walking assessment.
Time frame: Day 1
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 27 Oct 2016.
- Background: PubMed 23536810Fakhar K, Hastings E, Butson CR, Foote KD, Zeilman P, Okun MS. Management of deep brain stimulator battery failure: battery estimators, charge density, and importance of clinical symptoms. PLoS One. 2013;8(3):e58665. doi: 10.1371/journal.pone.0058665. Epub 2013 Mar 11.
- Background: PubMed 24548586Rawal PV, Almeida L, Smelser LB, Huang H, Guthrie BL, Walker HC. Shorter pulse generator longevity and more frequent stimulator adjustments with pallidal DBS for dystonia versus other movement disorders. Brain Stimul. 2014 May-Jun;7(3):345-9. doi: 10.1016/j.brs.2014.01.008. Epub 2014 Jan 18.
- Background: PubMed 21084732Foutz TJ, McIntyre CC. Evaluation of novel stimulus waveforms for deep brain stimulation. J Neural Eng. 2010 Dec;7(6):066008. doi: 10.1088/1741-2560/7/6/066008. Epub 2010 Nov 17.
- Background: PubMed 22007167Hofmann L, Ebert M, Tass PA, Hauptmann C. Modified pulse shapes for effective neural stimulation. Front Neuroeng. 2011 Sep 28;4:9. doi: 10.3389/fneng.2011.00009. eCollection 2011.
- Background: PubMed 24112880Brocker DT, Grill WM. Principles of electrical stimulation of neural tissue. Handb Clin Neurol. 2013;116:3-18. doi: 10.1016/B978-0-444-53497-2.00001-2.
- Background: PubMed 21994263Birdno MJ, Kuncel AM, Dorval AD, Turner DA, Gross RE, Grill WM. Stimulus features underlying reduced tremor suppression with temporally patterned deep brain stimulation. J Neurophysiol. 2012 Jan;107(1):364-83. doi: 10.1152/jn.00906.2010. Epub 2011 Oct 12.
- Background: PubMed 24118257Swan BD, Grill WM, Turner DA. Investigation of deep brain stimulation mechanisms during implantable pulse generator replacement surgery. Neuromodulation. 2014 Jul;17(5):419-24; discussion 424. doi: 10.1111/ner.12123. Epub 2013 Oct 7.
- Background: PubMed 24555921Beuter A, Lefaucheur JP, Modolo J. Closed-loop cortical neuromodulation in Parkinson's disease: An alternative to deep brain stimulation? Clin Neurophysiol. 2014 May;125(5):874-85. doi: 10.1016/j.clinph.2014.01.006. Epub 2014 Jan 18.
- Background: PubMed 23044532Okun MS, Foote KD, Wu SS, Ward HE, Bowers D, Rodriguez RL, Malaty IA, Goodman WK, Gilbert DM, Walker HC, Mink JW, Merritt S, Morishita T, Sanchez JC. A trial of scheduled deep brain stimulation for Tourette syndrome: moving away from continuous deep brain stimulation paradigms. JAMA Neurol. 2013 Jan;70(1):85-94. doi: 10.1001/jamaneurol.2013.580.
- University of Florida Center for Movement Disorders \& NeurorestorationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes
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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.
Leonardo Almeida, MD principal investigator
University of Florida Center for Movement Disorders and Neurorestoration
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 Dystonia and Cervical Dystonia, 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 4 inclusion and 1 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 27 Oct 2016. 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?
Blinded Unified Dystonia Rating Scale (UDRS) (time frame: Day 1). 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 NCT02468843, which also lists 9 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 27 Oct 2016.