Deep Brain Stimulation of the Globus Pallidus in Huntington's Disease

Study Description

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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).

Condition or disease	Intervention/treatment	Phase
Huntington's Disease	Procedure: Stimulation	Phase 1

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	6 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Single Centre (Pilot) Study for Deep Brain Stimulation (DBS) of the Globus Pallidus in Huntington's Disease (HD)
Study Start Date :	May 2009
Actual Primary Completion Date :	April 2012
Actual Study Completion Date :	July 2012

Arms and Interventions

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Arm	Intervention/treatment
Experimental: 1; 6 weeks stimulation with GPI (lower caudal two contacts), 4 weeks wash-out, 6 weeks stimulation with GPE (upper cranial two contacts).	Procedure: Stimulation; 6 weeks stimulation with GPI (lower caudal two contacts), 4 weeks wash-out, 6 weeks stimulation GPE (upper cranial two contacts); Other Names: GPI; GPE
Experimental: 2; 6 weeks stimulation with GPE (upper cranial two contacts), 4 weeks wash-out, 6 weeks stimulation with GPI (lower caudal two contacts)	Procedure: Stimulation; 6 weeks stimulation with GPE (upper cranial two contacts), 4 weeks wash-out, 6 weeks stimulation with GPI (lower caudal two contacts); Other Names: GPE; GPI

Outcome Measures

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Primary Outcome Measures :

1. Efficacy of stimulation of GPI versus GPR (UHDRS Scale) [ Time Frame: 3 months after stimulation treatment ]

Secondary Outcome Measures :

1. Effect of treatment on cognitive functions (neuropsychological tests) [ Time Frame: 3 months after stimulation treatment ]
2. Effects of treatment on electrophysiological tests [ Time Frame: 3 months after stimulation treatment ]
3. Effects of treatment on functional scale (functional ability, dependence scale, TFC) [ Time Frame: 3 months after stimulation treatment ]
4. Progression of disease (motor UHDRS) [ Time Frame: 12 months after stimulation treatment ]
5. Effect of treatment on striatal atrophy (CT Scans) [ Time Frame: 3 months after stimulation treatment ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Locations

Germany
Functional Neurosurgery and Stereotaxy, Department of Neurosurgery University Hospital Duesseldorf
Duesseldorf, NW, Germany, 40225

Sponsors and Collaborators

Heinrich-Heine University, Duesseldorf

Investigators

Principal Investigator:	Jan Vesper, Prof. Dr.	Functional Neurosurgery and Stereotaxy, Department of Neurosurgery

More Information

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Publications:

Temel Y, Cao C, Vlamings R, Blokland A, Ozen H, Steinbusch HW, Michelsen KA, von Hörsten 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. Epub 2006 Aug 14.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Beste C, Mückschel 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.

Responsible Party:	Heinrich-Heine University, Duesseldorf
ClinicalTrials.gov Identifier:	NCT00902889 History of Changes
Other Study ID Numbers:	Huntington
First Posted:	May 15, 2009
Last Update Posted:	September 11, 2012
Last Verified:	September 2012

Keywords provided by Heinrich-Heine University, Duesseldorf:

Globus pallidus; Huntington's Disease; Deep Brain Stimulation; Movement Disorders

Additional relevant MeSH terms:

Huntington Disease; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias	Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Cognition Disorders; Neurocognitive Disorders; Mental Disorders