Deep Brain Stimulation (DBS) of the Globus Pallidus (GP) in Huntington's Disease (HD) (HD-DBS)

Deep Brain Stimulation (DBS) of the Globus Pallidus (GP) in Huntington's Disease (HD): A Prospective, Randomised, Controlled, International, Multi-centre Study

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

Study Overview

• Status: Completed
• Conditions: Huntington Disease
• Intervention / Treatment: Device: ACTIVA® PC neurostimulator (Model 37601)

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Medizinische Universität Innsbruck
• France
  • Amiens, France, 80054
    • CHU Amiens Hôpital nord, Department of neurosurgery and Department of neurology
  • Lille Cedex, France, 59037
    • Hôpital Roger Salengro, Service de Neurologie et Pathologie du mouvement
• Germany
  • Berlin, Germany, 13353
    • Charite Campus Virchow Klinikum
  • Düsseldorf, Germany, 40225
    • University hospital Heinrich Heine University Düsseldorf
  • Freiburg, Germany, 79106
    • University Hospital Freiburg
  • Kiel, Germany, 24105
    • University Hospital Schleswig-Holstein
  • Lubeck Hansestadt, Germany, 23562
    • Universität zu Lübeck
  • Munich, Germany, 80336
    • University hospital Munich LMU
  • Taufkirchen, Germany, 84416
    • kbo-Isar-Amper-Clinic Taufkirchen
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital, Department of Neurology
  • Gümlingen
    • Bern, Gümlingen, Switzerland, 3073
      • Center for Neurology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stimulation group; Patients in the stimulation group will be stimulated immediately after implantation of the Stimulator (ACTIVA® PC neurostimulator (Model 37601))	Device: ACTIVA® PC neurostimulator (Model 37601); the stimulator in the stimulation group will be turned on after implantation of the device
Sham Comparator: Non-stimulation group; Patients in the non-stimulation group will not be stimulated for the first three months after implantation of the Stimulator (ACTIVA® PC neurostimulator (Model 37601))	Device: ACTIVA® PC neurostimulator (Model 37601); the stimulator in the stimulation group will be turned on after implantation of the device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
UHDRS-TMS difference	Difference between the groups in the UHDRS total motor score (UHDRS-TMS) at 12 weeks postoperatively compared to baseline.	12 weeks postoperatively compared to baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
UHDRS-Chorea difference	Difference in the Unified Huntington's Disease Rating Scale (UHDRS) chorea subscore (items 14-20)	6 months postoperatively compared to baseline
UHDRS-bradykinesia difference	Difference in the UHDRS bradykinesia subscore (items 22-25 and 27-29)	6 months postoperatively compared to baseline
BFMDRS difference	Difference in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor score	6 months postoperatively compared to baseline
Reilmann Battery differences	Difference in the Q-Motor "choreomotography" test (Reilmann Battery)	6 months postoperatively compared to baseline
MDRS difference	Difference in the Mattis Dementia Rating Scale (MDRS)	6 months postoperatively compared to baseline
Verbal Fluency Test difference	Difference in the Verbal Fluency Test (formal lexical, categorical, category change)	6 months postoperatively compared to baseline
SDMT difference	Difference in the Symbol Digit Modalities Test (SDMT)	6 months postoperatively compared to baseline
STROOP Test differences	Difference in STROOP word reading, colour naming and colour of the word naming	6 months postoperatively compared to baseline
HADS-SIS difference	Difference in the Hospital Anxiety and Depression Scale combined with Snaith Irritability Scale (HADS-SIS)	6 months postoperatively compared to baseline
PBA-s difference	Difference in the Problem Behaviours Assessment Short Form (PBA-s)	6 months postoperatively compared to baseline
SF 36 difference	Difference in the Short Form (36) Health Survey (SF-36)	6 months postoperatively compared to baseline
CGI difference	Difference in the Clinical Global Impression Scale (CGI)	6 months postoperatively compared to baseline

Collaborators and Investigators

• Sponsor: Heinrich-Heine University, Duesseldorf
• Collaborators: Medtronic; The George Institute; KKS Netzwerk; CHDI Foundation, Inc.; Egyptian Society of Neurological Surgeons
• Investigators: Study Chair: Jan Vesper, Prof Dr., Dept. of Functional Neurosurgery and Stereotaxy; Principal Investigator: Alfons Schnitzler, Prof Dr, Dept.of Neurology

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2014
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: August 27, 2015
• First Submitted That Met QC Criteria: August 28, 2015
• First Posted (Estimate): August 31, 2015

Study Record Updates

• Last Update Posted (Actual): January 21, 2022
• Last Update Submitted That Met QC Criteria: January 20, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Huntington Disease; DBS; Chorea
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Chorea; Huntington Disease
• Other Study ID Numbers: KKS-198; DRKS00006785 (Registry Identifier: Deutsches Register Klinischer Studien)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: After the study the data will be provided to the CHDI. The Foundation may use, and make available for use by the Foundation Collaborators, the Study Data for the following purposes: (A) to design and guide future research studies and clinical trials and (B) to support and enable the following scientific discussion and research: (1) to better understand HD or other diseases being studied, (2) that furthers the development of treatments for HD or other diseases or (3) that furthers biomedical research.