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

NCT02535884 | Completed DMC

• 2 other identifiers: KKS-198DRKS00006785
• Study Type: interventional
• Target: 48
• Locations: 4 countries
• Sites: 12

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

Conditions

Huntington Disease

Keywords

Huntington Disease; DBS; Chorea

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• UHDRS-Chorea difference

  6 months postoperatively compared to baseline

• UHDRS-bradykinesia difference

  6 months postoperatively compared to baseline

• BFMDRS difference

  6 months postoperatively compared to baseline

• Reilmann Battery differences

  6 months postoperatively compared to baseline

• MDRS difference

  6 months postoperatively compared to baseline

Study Arms (2)

Stimulation group

EXPERIMENTAL

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)

Non-stimulation group

SHAM COMPARATOR

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)

Interventions

ACTIVA® PC neurostimulator (Model 37601) DEVICE

the stimulator in the stimulation group will be turned on after implantation of the device

Non-stimulation group; Stimulation group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Signed informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Heinrich-Heine University, Duesseldorf: lead
• KKS Netzwerk: collaborator
• Medtronic: collaborator
• The George Institute: collaborator
• Egyptian Society of Neurological Surgeons: collaborator
• CHDI Foundation, Inc.: collaborator

Study Sites (12)

Medizinische Universität Innsbruck

Innsbruck, 6020, Austria

Location

CHU Amiens Hôpital nord, Department of neurosurgery and Department of neurology

Amiens, 80054, France

Location

Hôpital Roger Salengro, Service de Neurologie et Pathologie du mouvement

Lille, 59037, France

Location

Charité Campus Virchow Klinikum

Berlin, 13353, Germany

Location

University hospital Heinrich Heine University Düsseldorf

Düsseldorf, 40225, Germany

Location

University Hospital Freiburg

Freiburg im Breisgau, 79106, Germany

Location

University Hospital Schleswig-Holstein

Kiel, 24105, Germany

Location

Universität zu Lübeck

Lübeck, 23562, Germany

Location

University hospital Munich LMU

Munich, 80336, Germany

Location

kbo-Isar-Amper-Clinic Taufkirchen

Taufkirchen, 84416, Germany

Location

Center for Neurology

Bern, Gümlingen, 3073, Switzerland

Location

Inselspital, Department of Neurology

Bern, 3010, Switzerland

Location

Related Publications (8)

• Moro E, Lang AE, Strafella AP, Poon YY, Arango PM, Dagher A, Hutchison WD, Lozano AM. Bilateral globus pallidus stimulation for Huntington's disease. Ann Neurol. 2004 Aug;56(2):290-4. doi: 10.1002/ana.20183.

  PMID: 15293283 BACKGROUND

• Groiss SJ WL, Suedmeyer, M, Ploner M, Reck C, Voges J, SturmV, Timmermann L, Schnitzler A. Effect of bilateral pallidal deep brain stimulation in Huntington's disease: A case report. Mov Disord, Volume 21, Issue S15. Tenth International Congress of Parkinson's Disease and Movement Disorders. Kyoto 2006.

  BACKGROUND

• Fasano A, Cadeddu F, Guidubaldi A, Piano C, Soleti F, Zinzi P, Bentivoglio AR. The long-term effect of tetrabenazine in the management of Huntington disease. Clin Neuropharmacol. 2008 Nov-Dec;31(6):313-8. doi: 10.1097/WNF.0b013e318166da60.

  PMID: 19050408 BACKGROUND

• Wojtecki L, Groiss SJ, Ferrea S, Elben S, Hartmann CJ, Dunnett SB, Rosser A, Saft C, Sudmeyer M, Ohmann C, Schnitzler A, Vesper J; Surgical Approaches Working Group of the European Huntington's Disease Network (EHDN). A Prospective Pilot Trial for Pallidal Deep Brain Stimulation in Huntington's Disease. Front Neurol. 2015 Aug 18;6:177. doi: 10.3389/fneur.2015.00177. eCollection 2015.

  PMID: 26347707 BACKGROUND

• Wojtecki L, Groiss SJ, Hartmann CJ, Elben S, Omlor S, Schnitzler A, Vesper J. Deep Brain Stimulation in Huntington's Disease-Preliminary Evidence on Pathophysiology, Efficacy and Safety. Brain Sci. 2016 Aug 30;6(3):38. doi: 10.3390/brainsci6030038.

  PMID: 27589813 BACKGROUND

• Kinfe T, Del Vecchio A, Nussel M, Zhao Y, Stadlbauer A, Buchfelder M. Deep brain stimulation and stereotactic-assisted brain graft injection targeting fronto-striatal circuits for Huntington's disease: an update. Expert Rev Neurother. 2022 Sep;22(9):781-788. doi: 10.1080/14737175.2022.2091988. Epub 2022 Jun 29.

  PMID: 35766355 DERIVED

• Rodrigues FB, Ferreira JJ, Wild EJ. Huntington's Disease Clinical Trials Corner: June 2019. J Huntingtons Dis. 2019;8(3):363-371. doi: 10.3233/JHD-199003.

  PMID: 31381524 DERIVED

• Hartmann CJ, Groiss SJ, Vesper J, Schnitzler A, Wojtecki L. Brain stimulation in Huntington's disease. Neurodegener Dis Manag. 2016 Jun;6(3):223-36. doi: 10.2217/nmt-2016-0007. Epub 2016 May 27.

  PMID: 27230813 DERIVED

MeSH Terms

Conditions

Huntington Disease; Chorea

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Jan Vesper, Prof Dr.

  Dept. of Functional Neurosurgery and Stereotaxy

  STUDY CHAIR

• Alfons Schnitzler, Prof Dr

  Dept.of Neurology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 27, 2015
• First Posted: August 31, 2015
• Study Start: July 1, 2014
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: January 21, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will share

Locations

CH (2); DE (7); AU (1); FR (2)