Comparison of the Efficacy of Double Monopolar Versus Interleaving Stimulation Modes for Pallidal Deep Brain Stimulation

Primary Dystonia Clinical Trial

Official title:

Comparison of the Efficacy of Double Monopolar Versus Interleaving Stimulation Modes for the Deep Brain Stimulation Treatment of Primary Generalized or Segmental Dystonia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01497639
• Other study ID #: 760906
• Status: Completed
• Phase: N/A
• Start date: March 2012
• Est. completion date: June 7, 2018

Study information

• Verified date: November 2018
• Source: University of Pecs
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to compare the efficacy and the safety profile of the newly introduced interleaving stimulation mode to those of the standard double monopolar stimulation mode during pallidal deep brain stimulation of primary generalized or segmental dystonia.

Description:

Background:

For the treatment of drug-refractory dystonia, bilateral pallidal deep brain stimulation (GPi-DBS) is proven to be an efficient option. On average, 40-55% improvement on dystonia rating scales (DRS) could be achieved according to the results of multicenter trials lasting for years. However, a considerable portion (10-25%) of the patients experience minimal alleviation despite of good electrode placement. These patients can be regarded as non-responders to GPi-DBS defined as having either limited improvement (< 25% on DRS) or worsening. Besides adjusting the amplitude, frequency or pulse-width of stimulation, one can change the electrode configuration from the commonly applied single monopolar stimulation mode (one contact on the electrode is negative) to either double monopolar stimulation (two -usually adjacent- negative contacts on the electrode are stimulated with same amplitude and pulse-width values) or bipolar stimulation mode (one contact on the electrode is positive) in case of unsatisfactory outcomes. Although these techniques had been utilized in multicenter trials, non-responsiveness to GPi-DBS did occur. Recently the investigators have reported in the Movement Disorders that the newly introduced interleaving stimulation mode was superior to single or double monopolar stimulation in four patients who had initially (6-12 months after implantation) limited response to GPi DBS.

Aims of the study:

To systematically compare the efficacy and the side-effect profile of double monopolar stimulation mode to those of interleaving stimulation mode in a prospective, randomized, double-blind, and cross-over study.

Methods:

The investigators would enroll 20-25 patients with drug refractory segmental or generalized primary dystonia undergoing bilateral GPi-DBS implantation within a 2-3 year time frame. The inclusion and exclusion criteria would follow those of the study of Kupsch et al.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: June 7, 2018
• Est. primary completion date: June 7, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years to 75 Years

Eligibility

Inclusion Criteria:

• ages of 7 and 75 years

• marked disability owing to primary generalized or segmental dystonia, despite optimal pharmacologic treatment

• disease duration of at least 5 years.

Exclusion Criteria:

• previous brain surgery;

• cognitive impairment (< 120 points on the Mattis Dementia Rating Scale)

• moderate-to-severe depression (> 25 points on the Beck Depression Inventory)

• marked brain atrophy as detected by magnetic resonance imaging

• other medical or psychiatric coexisting disorders that could increase the surgical risk or interfere with completion of the trial

Related Conditions & MeSH terms

• Dystonia
• Dystonic Disorders
• Primary Dystonia

Intervention

Device:
• Interleaving stimulation mode (Medtronic)
Interleaving stimulation mode with constant frequency (125 Hz) and pulse-width (120us)parameters 'Interleavingr stimulation mode (Medtronic)'
• Double monopolar stimulation mode (Medtronic)
Double monopolar stimulation mode with constant frequency (125 Hz) and pulse-width (120us)parameters 'Double monopolar stimulation mode (Medtronic)'

Locations

Country	Name	City	State
Hungary	Department of Neurology, University of Pécs	Pécs	Baranya Megye

Sponsors (1)

Lead Sponsor	Collaborator
University of Pecs

Country where clinical trial is conducted

Hungary, 

References & Publications (7)

Kovács N, Janszky J, Nagy F, Balás I. Changing to interleaving stimulation might improve dystonia in cases not responding to pallidal stimulation. Mov Disord. 2012 Jan;27(1):163-5. doi: 10.1002/mds.23962. Epub 2011 Sep 28. — View Citation

Kupsch A, Benecke R, Müller J, Trottenberg T, Schneider GH, Poewe W, Eisner W, Wolters A, Müller JU, Deuschl G, Pinsker MO, Skogseid IM, Roeste GK, Vollmer-Haase J, Brentrup A, Krause M, Tronnier V, Schnitzler A, Voges J, Nikkhah G, Vesper J, Naumann M, Volkmann J; Deep-Brain Stimulation for Dystonia Study Group. Pallidal deep-brain stimulation in primary generalized or segmental dystonia. N Engl J Med. 2006 Nov 9;355(19):1978-90. — View Citation

Kupsch A, Tagliati M, Vidailhet M, Aziz T, Krack P, Moro E, Krauss JK. Early postoperative management of DBS in dystonia: programming, response to stimulation, adverse events, medication changes, evaluations, and troubleshooting. Mov Disord. 2011 Jun;26 Suppl 1:S37-53. doi: 10.1002/mds.23624. Review. — View Citation

Tagliati M, Krack P, Volkmann J, Aziz T, Krauss JK, Kupsch A, Vidailhet AM. Long-Term management of DBS in dystonia: response to stimulation, adverse events, battery changes, and special considerations. Mov Disord. 2011 Jun;26 Suppl 1:S54-62. doi: 10.1002/mds.23535. Review. — View Citation

Valldeoriola F, Regidor I, Mínguez-Castellanos A, Lezcano E, García-Ruiz P, Rojo A, Salvador A, Castro A, Grandas F, Kulisevsky J, Martí MJ, Martínez-Martín P, Relova L, Rumià J, Cámara A, Burguera JA, Linazasoro G, de Val JL, Obeso J, Rodríguez-Oroz MC, Tolosa E; Grupo ESpañol para el EStudio de la EStimulación PALidal en la DIStonía. Efficacy and safety of pallidal stimulation in primary dystonia: results of the Spanish multicentric study. J Neurol Neurosurg Psychiatry. 2010 Jan;81(1):65-9. doi: 10.1136/jnnp.2009.174342. Epub 2009 Sep 10. — View Citation

Vidailhet M, Vercueil L, Houeto JL, Krystkowiak P, Benabid AL, Cornu P, Lagrange C, Tézenas du Montcel S, Dormont D, Grand S, Blond S, Detante O, Pillon B, Ardouin C, Agid Y, Destée A, Pollak P; French Stimulation du Pallidum Interne dans la Dystonie (SPIDY) Study Group. Bilateral deep-brain stimulation of the globus pallidus in primary generalized dystonia. N Engl J Med. 2005 Feb 3;352(5):459-67. — View Citation

Vidailhet M, Vercueil L, Houeto JL, Krystkowiak P, Lagrange C, Yelnik J, Bardinet E, Benabid AL, Navarro S, Dormont D, Grand S, Blond S, Ardouin C, Pillon B, Dujardin K, Hahn-Barma V, Agid Y, Destée A, Pollak P; French SPIDY Study Group. Bilateral, pallidal, deep-brain stimulation in primary generalised dystonia: a prospective 3 year follow-up study. Lancet Neurol. 2007 Mar;6(3):223-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Differences in severity of dystonia	Differences in severity of dystonia measured by Burke-Fahn-Marsden Dystonia Rating Scale	7 months
Secondary	Number of treatment responders after three months deep brain stimulation	Differences in number of treatment responders (at least 25% improvement on Burke-Fahn-Marsden Dystonia Rating Scale compared to baseline)	7 months
Secondary	Health-related quality of life after three months deep brain stimulation	Differences in health-related quality of life measured by EQ-5D and SF-36 scales	7 months
Secondary	Side-effect profile after three months deep brain stimulation	Differences in side-effect profile measured by stuctured deep brain stimulation-related side-effect questionnaire	7 months