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

Single Centre (Pilot) Study for Deep Brain Stimulation (DBS) of the Globus Pallidus in Huntington's Disease (HD)

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).

Study Overview

• Status: Completed
• Conditions: Huntington's Disease
• Intervention / Treatment: Procedure: Stimulation; Procedure: Stimulation

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 Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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; 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: 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 GPI (lower caudal two contacts), 4 weeks wash-out, 6 weeks stimulation GPE (upper cranial two contacts); Other Names: GPI; GPE; 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: GPI; GPE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Efficacy of stimulation of GPI versus GPR (UHDRS Scale)	3 months after stimulation treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Effect of treatment on cognitive functions (neuropsychological tests)	3 months after stimulation treatment
Effects of treatment on electrophysiological tests	3 months after stimulation treatment
Effects of treatment on functional scale (functional ability, dependence scale, TFC)	3 months after stimulation treatment
Progression of disease (motor UHDRS)	12 months after stimulation treatment
Effect of treatment on striatal atrophy (CT Scans)	3 months after stimulation treatment

Collaborators and Investigators

• Sponsor: Heinrich-Heine University, Duesseldorf
• Investigators: Principal Investigator: Jan Vesper, Prof. Dr., Functional Neurosurgery and Stereotaxy, Department of Neurosurgery

Publications and helpful links

General Publications

• 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.
• 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, 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: May 14, 2009
• First Submitted That Met QC Criteria: May 14, 2009
• First Posted (Estimate): May 15, 2009

Study Record Updates

• Last Update Posted (Estimate): September 11, 2012
• Last Update Submitted That Met QC Criteria: September 10, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: Movement Disorders; Deep Brain Stimulation; Huntington's Disease; Globus pallidus
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Chorea; Huntington Disease
• Other Study ID Numbers: Huntington