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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Huntington Disease

Intervention / Treatment
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* Device: ACTIVA® PC neurostimulator (Model 37601)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stimulation group<br>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)<br>* the stimulator in the stimulation group will be turned on after implantation of the device<br>|
| Sham Comparator: Non-stimulation group<br>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)<br>* the stimulator in the stimulation group will be turned on after implantation of the device<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Huntington Disease, DBS, Chorea