Huntington Disease
Conditions
Keywords
Huntington Disease, DBS, Chorea
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.
Interventions
DEVICEACTIVA® PC neurostimulator (Model 37601)
the stimulator in the stimulation group will be turned on after implantation of the device
Sponsors
KKS Netzwerk
Medtronic
The George Institute
Egyptian Society of Neurological Surgeons
CHDI Foundation, Inc.
Heinrich-Heine University, Duesseldorf
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| UHDRS-TMS difference | 12 weeks postoperatively compared to baseline | Difference between the groups in the UHDRS total motor score (UHDRS-TMS) at 12 weeks postoperatively compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| UHDRS-bradykinesia difference | 6 months postoperatively compared to baseline | Difference in the UHDRS bradykinesia subscore (items 22-25 and 27-29) |
| BFMDRS difference | 6 months postoperatively compared to baseline | Difference in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor score |
| Reilmann Battery differences | 6 months postoperatively compared to baseline | Difference in the Q-Motor choreomotography test (Reilmann Battery) |
| MDRS difference | 6 months postoperatively compared to baseline | Difference in the Mattis Dementia Rating Scale (MDRS) |
| Verbal Fluency Test difference | 6 months postoperatively compared to baseline | Difference in the Verbal Fluency Test (formal lexical, categorical, category change) |
| UHDRS-Chorea difference | 6 months postoperatively compared to baseline | Difference in the Unified Huntington's Disease Rating Scale (UHDRS) chorea subscore (items 14-20) |
| STROOP Test differences | 6 months postoperatively compared to baseline | Difference in STROOP word reading, colour naming and colour of the word naming |
| HADS-SIS difference | 6 months postoperatively compared to baseline | Difference in the Hospital Anxiety and Depression Scale combined with Snaith Irritability Scale (HADS-SIS) |
| PBA-s difference | 6 months postoperatively compared to baseline | Difference in the Problem Behaviours Assessment Short Form (PBA-s) |
| SF 36 difference | 6 months postoperatively compared to baseline | Difference in the Short Form (36) Health Survey (SF-36) |
| CGI difference | 6 months postoperatively compared to baseline | Difference in the Clinical Global Impression Scale (CGI) |
| SDMT difference | 6 months postoperatively compared to baseline | Difference in the Symbol Digit Modalities Test (SDMT) |
Countries
Austria, France, Germany, Switzerland
Outcome results
None listed