Clinical trial NCT02535884: Deep Brain Stimulation (DBS) of the Globus Pallidus (GP) in Huntington's Disease (HD)
Official title: Deep Brain Stimulation (DBS) of the Globus Pallidus (GP) in Huntington's Disease (HD): A Prospective, Randomised, Controlled, International, Multi-centre Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Huntington Disease
Keywords: Huntington Disease
DBS
Chorea
Lead sponsor: Heinrich-Heine University, Duesseldorf
Sponsor class: OTHER
Collaborators: name: KKS Netzwerk
name: Medtronic
name: The George Institute
name: Egyptian Society of Neurological Surgeons
name: CHDI Foundation, Inc.
First posted: 2015-08-31
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: During the first 3 month the one group will be stimulated (pallidal DBS), thereafter 12 weeks open follow up, where patients in both groups are stimulated.
Primary purpose: TREATMENT

Brief summary: The aim of the study is to prove the efficacy and safety of pallidal DBS in HD patients and to show superiority of DBS on motor function in the stimulation group compared to stimulation-off group

Detailed description: In this study the efficacy and safety of pallidal Deep Brain Stimulation (DBS) in HD patients shall be investigated and superiority of DBS on motor function in the stimulation group compared to the stimulation-off group shall be shown. This study is a prospective, randomised, double blind, parallel group, sham-controlled, multi-centre trial. Patients in the stimulation group will be stimulated for three months while the stimulator in the sham-group will be turned off for three months. After three months the primary endpoint will be assessed. Afterwards the stimulator will be turned on in all patients.

Eligibility criteria: Inclusion Criteria:

* Clinically symptomatic and genetically confirmed HD (number of CAG repeats ≥ 36)
* Age ≥18 years
* Moderate stage of the disease (UHDRS motor score ≥ 30)
* Chorea despite best medical treatment (UHDRS chorea subscore ≥ 10)
* Mattis Dementia Rating Scale ≥ 120 (or \> 80% of items testable independently from motor impairment)
* Patient has stable medication prior six weeks before inclusion
* Signed informed consent

Exclusion Criteria:

* Juvenile HD (Westphal variant) or predominant bradykinesia
* Postural instability with UHDRS retropulsion score \> 2
* Severe comorbidity compromising operability and/or life expectancy and/or quality of life during the trial duration (e.g. cancer with life expectancy \< 6 months, NYHA 3 and 4 rising the anaesthetic risk according to the anaesthesiologist)
* Acute suicidality
* Acute psychosis (symptoms within previous 6 months)
* Participation in any interventional clinical trial within 2 months before screening
* Cortical atrophy grade 3
* Patients with risk of coagulopathies and/or increased risk of haemorrhage
* Patients with an implanted pacemaker or defibrillator
* Pregnancy
* lactation

Primary outcomes:
measure: UHDRS-TMS difference
timeFrame: 12 weeks postoperatively compared to baseline
Secondary outcomes:
measure: UHDRS-Chorea difference
timeFrame: 6 months postoperatively compared to baseline
measure: UHDRS-bradykinesia difference
timeFrame: 6 months postoperatively compared to baseline
measure: BFMDRS difference
timeFrame: 6 months postoperatively compared to baseline
measure: Reilmann Battery differences
timeFrame: 6 months postoperatively compared to baseline
measure: MDRS difference
timeFrame: 6 months postoperatively compared to baseline
measure: Verbal Fluency Test difference
timeFrame: 6 months postoperatively compared to baseline
measure: SDMT difference
timeFrame: 6 months postoperatively compared to baseline
measure: STROOP Test differences
timeFrame: 6 months postoperatively compared to baseline
measure: HADS-SIS difference
timeFrame: 6 months postoperatively compared to baseline
measure: PBA-s difference
timeFrame: 6 months postoperatively compared to baseline
measure: SF 36 difference
timeFrame: 6 months postoperatively compared to baseline
measure: CGI difference
timeFrame: 6 months postoperatively compared to baseline
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Amiens
country: France
facility: CHU Amiens Hôpital nord, Department of neurosurgery and Department of neurology
city: Lille Cedex
country: France
facility: Hôpital Roger Salengro, Service de Neurologie et Pathologie du mouvement
city: Berlin
country: Germany
facility: Charité Campus Virchow Klinikum
city: Düsseldorf
country: Germany
facility: University hospital Heinrich Heine University Düsseldorf
city: Freiburg
country: Germany
facility: University Hospital Freiburg
city: Kiel
country: Germany
facility: University Hospital Schleswig-Holstein
city: Lubeck Hansestadt
country: Germany
facility: Universität zu Lübeck
city: Munich
country: Germany
facility: University hospital Munich LMU
city: Taufkirchen
country: Germany
facility: kbo-Isar-Amper-Clinic Taufkirchen
city: Bern
country: Switzerland
facility: Center for Neurology
state: Gümlingen
city: Bern
country: Switzerland
facility: Inselspital, Department of Neurology
Study officials:
affiliation: Dept. of Functional Neurosurgery and Stereotaxy
name: Jan Vesper, Prof Dr.
role: STUDY_CHAIR
affiliation: Dept.of Neurology
name: Alfons Schnitzler, Prof Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Moro E, Lang AE, Strafella AP, Poon YY, Arango PM, Dagher A, Hutchison WD, Lozano AM. Bilateral globus pallidus stimulation for Huntington's disease. Ann Neurol. 2004 Aug;56(2):290-4. doi: 10.1002/ana.20183.
citation: Groiss SJ WL, Suedmeyer, M, Ploner M, Reck C, Voges J, SturmV, Timmermann L, Schnitzler A. Effect of bilateral pallidal deep brain stimulation in Huntington's disease: A case report. Mov Disord, Volume 21, Issue S15. Tenth International Congress of Parkinson's Disease and Movement Disorders. Kyoto 2006.
citation: Fasano A, Cadeddu F, Guidubaldi A, Piano C, Soleti F, Zinzi P, Bentivoglio AR. The long-term effect of tetrabenazine in the management of Huntington disease. Clin Neuropharmacol. 2008 Nov-Dec;31(6):313-8. doi: 10.1097/WNF.0b013e318166da60.
citation: Wojtecki L, Groiss SJ, Ferrea S, Elben S, Hartmann CJ, Dunnett SB, Rosser A, Saft C, Sudmeyer M, Ohmann C, Schnitzler A, Vesper J; Surgical Approaches Working Group of the European Huntington's Disease Network (EHDN). A Prospective Pilot Trial for Pallidal Deep Brain Stimulation in Huntington's Disease. Front Neurol. 2015 Aug 18;6:177. doi: 10.3389/fneur.2015.00177. eCollection 2015.
citation: Wojtecki L, Groiss SJ, Hartmann CJ, Elben S, Omlor S, Schnitzler A, Vesper J. Deep Brain Stimulation in Huntington's Disease-Preliminary Evidence on Pathophysiology, Efficacy and Safety. Brain Sci. 2016 Aug 30;6(3):38. doi: 10.3390/brainsci6030038.
citation: Rodrigues FB, Ferreira JJ, Wild EJ. Huntington's Disease Clinical Trials Corner: June 2019. J Huntingtons Dis. 2019;8(3):363-371. doi: 10.3233/JHD-199003.
citation: Hartmann CJ, Groiss SJ, Vesper J, Schnitzler A, Wojtecki L. Brain stimulation in Huntington's disease. Neurodegener Dis Manag. 2016 Jun;6(3):223-36. doi: 10.2217/nmt-2016-0007. Epub 2016 May 27.