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

Huntington Disease Clinical Trial

— HD-DBS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02535884
• Other study ID #: KKS-198
• Secondary ID: DRKS00006785
• Status: Completed
• Phase: N/A
• Start date: July 2014
• Est. completion date: December 31, 2021

Study information

• Verified date: January 2022
• Source: Heinrich-Heine University, Duesseldorf
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Huntington Disease

Intervention

Device:
• ACTIVA® PC neurostimulator (Model 37601)
the stimulator in the stimulation group will be turned on after implantation of the device

Locations

Country	Name	City	State
Austria	Medizinische Universität Innsbruck	Innsbruck
France	CHU Amiens Hôpital nord, Department of neurosurgery and Department of neurology	Amiens
France	Hôpital Roger Salengro, Service de Neurologie et Pathologie du mouvement	Lille Cedex
Germany	Charité Campus Virchow Klinikum	Berlin
Germany	University hospital Heinrich Heine University Düsseldorf	Düsseldorf
Germany	University Hospital Freiburg	Freiburg
Germany	University Hospital Schleswig-Holstein	Kiel
Germany	Universität zu Lübeck	Lubeck Hansestadt
Germany	University hospital Munich LMU	Munich
Germany	kbo-Isar-Amper-Clinic Taufkirchen	Taufkirchen
Switzerland	Center for Neurology	Bern	Gümlingen
Switzerland	Inselspital, Department of Neurology	Bern

Sponsors (6)

Lead Sponsor	Collaborator
Heinrich-Heine University, Duesseldorf	CHDI Foundation, Inc., Egyptian Society of Neurological Surgeons, KKS Netzwerk, Medtronic, The George Institute

Countries where clinical trial is conducted

Austria,  France,  Germany,  Switzerland, 

References & Publications (5)

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. — View 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.

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. — View Citation

Wojtecki L, Groiss SJ, Ferrea S, Elben S, Hartmann CJ, Dunnett SB, Rosser A, Saft C, Südmeyer 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. — View 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). pii: E38. doi: 10.3390/brainsci6030038. Review. — View Citation

Outcome

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