Novel Stimulation Patterns for the Treatment of Dystonia

Dystonia Clinical Trial

Official title:

Novel Stimulation Patterns and Personalized Deep Brain Stimulation for the Treatment of Dystonia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02468843
• Other study ID #: IRB201500366
• Status: Completed
• Phase: N/A
• First received: June 3, 2015
• Last updated: October 25, 2016
• Start date: July 2015
• Est. completion date: August 2016

Study information

• Verified date: October 2016
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical 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). 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: August 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Cervical Dystonia
• Dystonia
• Dystonic Disorders
• Torticollis

Intervention

Device:
• Biphasic DBS stimulation
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)

Other:
• Unified Dystonia Rating Scale
Neurologist use the UDRS to determine the severity and duration of dystonia on 14 body areas.
• Burke-Fahn- Marsden scale
Neurologist use the BFMDRS to rate the severity of dystonia in 9 regions of the body.

Locations

Country	Name	City	State
United States	Center for Movement Disorders and Neurorestoration	Gainesville	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of Florida	Medtronic

Country where clinical trial is conducted

United States, 

References & Publications (9)

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. Review. — View Citation

Birdno 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. — View Citation

Brocker 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. Review. — View Citation

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. — View Citation

Foutz 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. — View Citation

Hofmann 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. — View 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. — View 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. — View Citation

Swan 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day 1	No
Primary	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.	Day 1	No
Secondary	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).	Day 1	No
Secondary	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).	Day 1	No
Secondary	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.	Day 2	No
Secondary	GaitRite walking assessment.	The GaitRite is an automated floor that when you walk on the floor it records your gait pattern.	Day 1	No

External Links

•   University of Florida Center for Movement Disorders & Neurorestoration