Novel Stimulation Patterns for the Treatment of Dystonia

NCT02468843 | Completed

• 1 other identifier: IRB201500366
• Study Type: observational
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Dystonia; Cervical Dystonia

Keywords

Deep brain stimulation; DBS; Dystonia; DYT1

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (4)

• Tremor accelerometer to measure motor dysfunction

  Day 1

• Kinesia accelerometer to measure motor dysfunction

  Day 1

• Battery Consumption compared between pre and post settings

  Day 2

• GaitRite walking assessment.

  Day 1

Study Arms (1)

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.

Device: Biphasic DBS stimulation; Other: Unified Dystonia Rating Scale; Other: Burke-Fahn- Marsden scale

Interventions

Biphasic DBS stimulation DEVICE

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. 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)

Biphasic DBS stimulations

Unified Dystonia Rating Scale OTHER

Neurologist use the UDRS to determine the severity and duration of dystonia on 14 body areas.

Also known as: UDRS

Biphasic DBS stimulations

Burke-Fahn- Marsden scale OTHER

Neurologist use the BFMDRS to rate the severity of dystonia in 9 regions of the body.

Also known as: BFMDRS

Biphasic DBS stimulations

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• Does not have DBS for dystonia or cervical dystonia

Sponsors & Collaborators

• University of Florida: lead
• Medtronic: collaborator

Study Sites (1)

Center for Movement Disorders and Neurorestoration

Gainesville, Florida, 32607, United States

Location

Related Publications (9)

• 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.

  PMID: 23536810 BACKGROUND

• 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.

  PMID: 24548586 BACKGROUND

• 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. Epub 2010 Nov 17.

  PMID: 21084732 BACKGROUND

• 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. eCollection 2011.

  PMID: 22007167 BACKGROUND

• 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.

  PMID: 24112880 BACKGROUND

• 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. Epub 2011 Oct 12.

  PMID: 21994263 BACKGROUND

• 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. Epub 2013 Oct 7.

  PMID: 24118257 BACKGROUND

• 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.

  PMID: 24555921 BACKGROUND

• 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.

  PMID: 23044532 BACKGROUND

Related Links

• University of Florida Center for Movement Disorders \& Neurorestoration

MeSH Terms

Conditions

Dystonia; Torticollis; Dystonia musculorum deformans type 1

Condition Hierarchy (Ancestors)

Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Leonardo Almeida, MD

  University of Florida Center for Movement Disorders and Neurorestoration

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2015
• First Posted: June 11, 2015
• Study Start: July 1, 2015
• Primary Completion: January 1, 2016
• Study Completion: August 1, 2016
• Last Updated: October 27, 2016

Record last verified: 2016-10

Data Sharing

• IPD Sharing: Will share

Locations

US (1)