Clinical trial NCT02468843: Novel Stimulation Patterns for the Treatment of Dystonia
Official title: Novel Stimulation Patterns and Personalized Deep Brain Stimulation for the Treatment of Dystonia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Dystonia
Cervical Dystonia
Keywords: Deep brain stimulation
DBS
Dystonia
DYT1
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: Medtronic
First posted: 2015-06-11
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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). 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* Does not have DBS for dystonia or cervical dystonia

Primary outcomes:
measure: Blinded Unified Dystonia Rating Scale (UDRS)
timeFrame: Day 1
measure: Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS)
timeFrame: Day 1
Secondary outcomes:
measure: Tremor accelerometer to measure motor dysfunction
timeFrame: Day 1
measure: Kinesia accelerometer to measure motor dysfunction
timeFrame: Day 1
measure: Battery Consumption compared between pre and post settings
timeFrame: Day 2
measure: GaitRite walking assessment.
timeFrame: Day 1
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: Center for Movement Disorders and Neurorestoration
state: Florida
Study officials:
affiliation: University of Florida Center for Movement Disorders and Neurorestoration
name: Leonardo Almeida, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Rawal 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.
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citation: Beuter 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.
citation: Okun 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.