Clinical trial NCT01497639: Comparison of the Efficacy of Double Monopolar Versus Interleaving Stimulation Modes for Pallidal Deep Brain Stimulation
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Primary Dystonia
Keywords: dystonia
pallidal stimulation
deep brain stimulation
deep brain stimulation of GPi
GPi
interleaving stimulation
Lead sponsor: University of Pecs
Sponsor class: OTHER
First posted: 2011-12-22
Enrollment: 34
Sex: ALL
Minimum age (years): 7
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Differences in severity of dystonia
timeFrame: 7 months
Secondary outcomes:
measure: Number of treatment responders after three months deep brain stimulation
timeFrame: 7 months
measure: Health-related quality of life after three months deep brain stimulation
timeFrame: 7 months
measure: Side-effect profile after three months deep brain stimulation
timeFrame: 7 months
Other outcomes:
Locations:
city: Pécs
country: Hungary
facility: Department of Neurology, University of Pécs
state: Baranya Megye
Study officials:
affiliation: Associate professor, Department of Neurology, University of Pecs
name: Norbert Kovacs, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kupsch A, Benecke R, Muller J, Trottenberg T, Schneider GH, Poewe W, Eisner W, Wolters A, Muller 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. doi: 10.1056/NEJMoa063618.
citation: Vidailhet M, Vercueil L, Houeto JL, Krystkowiak P, Benabid AL, Cornu P, Lagrange C, Tezenas du Montcel S, Dormont D, Grand S, Blond S, Detante O, Pillon B, Ardouin C, Agid Y, Destee 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. doi: 10.1056/NEJMoa042187.
citation: Valldeoriola F, Regidor I, Minguez-Castellanos A, Lezcano E, Garcia-Ruiz P, Rojo A, Salvador A, Castro A, Grandas F, Kulisevsky J, Marti MJ, Martinez-Martin P, Relova L, Rumia J, Camara A, Burguera JA, Linazasoro G, de Val JL, Obeso J, Rodriguez-Oroz MC, Tolosa E; Grupo ESpanol para el EStudio de la EStimulacion PALidal en la DIStonia. 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.
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, Destee 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. doi: 10.1016/S1474-4422(07)70035-2.
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.
citation: Kovacs N, Janszky J, Nagy F, Balas 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. No abstract available.
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.