Clinical trial NCT00902889: Deep Brain Stimulation of the Globus Pallidus in Huntington's Disease
Official title: Single Centre (Pilot) Study for Deep Brain Stimulation (DBS) of the Globus Pallidus in Huntington's Disease (HD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Huntington's Disease
Keywords: Globus pallidus
Huntington's Disease
Deep Brain Stimulation
Movement Disorders
Lead sponsor: Heinrich-Heine University, Duesseldorf
Sponsor class: OTHER
First posted: 2009-05-15
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This is a single centre, controlled phase I study, which evaluates safety and efficacy of stimulation of lower caudal two contacts (GPI) vs. upper cranial two contacts (GPE) in Huntington´s disease (HD).

Detailed description: A total of 6 HD patients will be selected out of an existing larger HD patient cohort upon careful evaluation of the inclusion and exclusion criteria at month 0. Patients will be recruited if no significant cognitive deterioration is observed between month 0 and month 3. The preoperative clinical status will be evaluated twice including the United Huntington Disease Rating Scale (UHDRS), neuropsychological, neurophysiologic and neuroradiological assessments. At 4 weeks postoperatively an extensive evaluation of effects and side effects of every single contact of the bilateral quadripolar electrodes takes place.

All patients will receive a stereotactic placement of bilateral stereotactic insertion of two quadripolar electrodes into the Globus pallidus, two contacts reaching the GPE, two the GPI within both hemispheres. Surgery will be done under general anesthesia, The implantation of the stimulator (Kintera®) will take place in the same procedure. Postoperatively patients will be monitored at three and six months and regularly up to 60 months with a battery of clinical, neuropsychological, psychiatric, neurophysiological and neuroimaging tests.

We expect that this trial will provide a rational basis to conclude about the efficacy, safety, reproducibility and long-term effects of pallidal Deep Brain Stimulation (DBS) on motor symptoms of HD.

Eligibility criteria: Inclusion Criteria:

* clinically symptomatic and genetically confirmed Huntington Disease (number of CAG repeats\>= 36)
* age: \> 18
* moderate stage of the disease (UHDRS motor\>= 30)
* predominant movement disorder
* compliance of the patient, stable cognition during a 6 months phase prior to inclusion (MDS\>/= 120)
* signed informed consent

Exclusion Criteria:

* advanced disease, precluding the ability to give informed consent
* very early stage of disease causing minor disability
* severe comorbidity that could compromise the life prognostic or preclude general anaesthesia or immunosuppression
* Mattis Dementia Rating Scale \< 120
* psychiatric or personality disturbances that might compromise the follow-up
* participation at another trial (in particular transplantation)
* severe cortical atrophy seen on CT and MRI

Primary outcomes:
measure: Efficacy of stimulation of GPI versus GPR (UHDRS Scale)
timeFrame: 3 months after stimulation treatment
Secondary outcomes:
measure: Effect of treatment on cognitive functions (neuropsychological tests)
timeFrame: 3 months after stimulation treatment
measure: Effects of treatment on electrophysiological tests
timeFrame: 3 months after stimulation treatment
measure: Effects of treatment on functional scale (functional ability, dependence scale, TFC)
timeFrame: 3 months after stimulation treatment
measure: Progression of disease (motor UHDRS)
timeFrame: 12 months after stimulation treatment
measure: Effect of treatment on striatal atrophy (CT Scans)
timeFrame: 3 months after stimulation treatment
Other outcomes:
Locations:
city: Duesseldorf
country: Germany
facility: Functional Neurosurgery and Stereotaxy, Department of Neurosurgery University Hospital Duesseldorf
state: NW
Study officials:
affiliation: Functional Neurosurgery and Stereotaxy, Department of Neurosurgery
name: Jan Vesper, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Temel Y, Cao C, Vlamings R, Blokland A, Ozen H, Steinbusch HW, Michelsen KA, von Horsten S, Schmitz C, Visser-Vandewalle V. Motor and cognitive improvement by deep brain stimulation in a transgenic rat model of Huntington's disease. Neurosci Lett. 2006 Oct 2;406(1-2):138-41. doi: 10.1016/j.neulet.2006.07.036. Epub 2006 Aug 14.
citation: Ferrea S, Groiss SJ, Elben S, Hartmann CJ, Dunnett SB, Rosser A, Saft C, Schnitzler A, Vesper J, Wojtecki L; Surgical Approaches Working Group of the European Huntington's Disease Network (EHDN). Pallidal deep brain stimulation in juvenile Huntington's disease: local field potential oscillations and clinical data. J Neurol. 2018 Jul;265(7):1573-1579. doi: 10.1007/s00415-018-8880-1. Epub 2018 May 3.
citation: Beste C, Muckschel M, Elben S, J Hartmann C, McIntyre CC, Saft C, Vesper J, Schnitzler A, Wojtecki L. Behavioral and neurophysiological evidence for the enhancement of cognitive control under dorsal pallidal deep brain stimulation in Huntington's disease. Brain Struct Funct. 2015 Jul;220(4):2441-8. doi: 10.1007/s00429-014-0805-x. Epub 2014 May 31.