Combined Stimulation of STN and SNr for Resistant Freezing of Gait in Parkinson's Disease

NCT ID: NCT02588144

Last Updated: 2017-06-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2017-09-30

Brief Summary

54 patients with idiopathic Parkinson's disease and freezing of gait resistant to subthalamic nucleus stimulation and dopaminergic medication will be included into this multicentre randomised controlled double-blinded parallel group clinical trial. The treatment consists of two different stimulation settings using (i) conventional stimulation of the subthalamic nucleus [standard STN] as active comparator and (ii) combined stimulation of active electrode contacts located in both the subthalamic nucleus and substantia nigra pars reticulata [STN+SNr].

Detailed Description

The primary endpoint of this study is to investigate the efficacy and safety of combined [STN+SNr] stimulation by "interleaving stimulation" as compared to [standardSTN] after 3 months on refractory freezing of gait (FOG). The Trial is designed as superiority study with an 80% power to detect a mean improvement of 4.7 points on the Freezing of Gait Assessment Course (Ziegler et al., 2010) with one-tailed P < 0.2. To this end 54 patients will be studied. After a common baseline assessment in [standardSTN], patients will be randomized to either [standardSTN] or [STN+SNr] in 1:1 ratio (27 per arm). The primary endpoint assessment is scheduled 90 days from baseline assessment (V6). Additional interim visits are scheduled for secondary purpose from baseline at day 2 (V2), day 8 (V3), day 21 (V4), day 42 (V5).

The rationale for this study comes from our previous phase II trial (Weiss et al., 2013) in which we have observed an improvement of freezing of gait from combined STN+SNr stimulation as secondary endpoint compared with standard STN stimulation at three-week follow-up.

Secondary outcome measures include anamnestic assessments on freezing of gait and falls, balance, quality of life, neuropsychiatric symptoms and suicidality.

Conditions

Parkinson's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

[standard STN]

Device: standard stimulation on subthalamic (STN) contacts

Group Type: ACTIVE_COMPARATOR

[standard STN]

Intervention Type: PROCEDURE

High frequency deep brain stimulation with variable (best individual) stimulation on subthalamic contacts

[STN+SNr]

Device: Combined stimulation of the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr)

Group Type: EXPERIMENTAL

[STN+SNr]

Intervention Type: PROCEDURE

high frequency deep brain stimulation of combined (best individual) subthalamic and nigral stimulation

Interventions

[standard STN]

High frequency deep brain stimulation with variable (best individual) stimulation on subthalamic contacts

Intervention Type: PROCEDURE

[STN+SNr]

high frequency deep brain stimulation of combined (best individual) subthalamic and nigral stimulation

Intervention Type: PROCEDURE

Other Intervention Names

subthalamic deep brain stimulation; combined subthalamic and nigral stimulation

Eligibility Criteria

Inclusion Criteria

• Idiopathic Parkinson's disease (according to the "British Brain Bank criteria" (Hughes, 1992) including genetic forms
• Therapy with STN-DBS (deep brain stimulation) (ACTIVA pulse generators) at least six months from surgery
• Activa PC (Primary Cell) or Activa RC (Rechargeable Cell) as implanted pulse generator with "Interleaving" programming option
• Localization of an active electrode contact in the subthalamic nucleus
• Localization of the caudal electrode contacts in the substantia nigra pars reticulata area (coordinates relative to midcommisural Point (MCP):

left: -7mm ≤ x ≤ -12mm; -2mm ≤ y ≤ -6mm; -6mm ≤ z ≤ -10mm right: 7mm ≤ x ≤ 12mm; -2mm ≤ y ≤ -6mm; -6mm ≤ z ≤ -10mm (x = medio-lateral, y = anterio-posterior, z = rostro-caudal)

• ≥ 30% improvement in UPDRS III with 'standard STN' compared to 'stimulation off' in dopaminergic off
• Freezing of Gait Assessment Course ≥10 and ≤33
• Patient not wheelchair-bound and possible to move self-dependently outside a freezing episode.
• Disease duration ≥ 5 years
• Age: between 18 and 80 years
• Dopaminergic medication constant for at least four weeks prior to study enrolment
• Written informed consent

Exclusion Criteria

• Participation in other clinical trials within the past three months and during enrolment in our study
• Cognitive impairment (Mini Mental State Exam < 20)
• Suicidality, Psychosis
• Other severe pathological chronic condition that might confound treatment effects or interpretation of the data
• Pregnancy
• Paradoxical levodopa-induced "on" state freezing (Espay et al., 2012)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medtronic

INDUSTRY

Sponsor Role: collaborator

University Hospital Tuebingen

OTHER

Sponsor Role: lead

Responsible Party

Daniel Weiss

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daniel Weiss, MD

Role: PRINCIPAL_INVESTIGATOR

Department for Neurodegenerative Diseases, Centre for Neurology, Tübingen, Germany, and Hertie-Institute for Clinical Brain Research

Alireza Gharabaghi, MD

Role: PRINCIPAL_INVESTIGATOR

Division of Functional and Restorative Neurosurgery, Department of Neurosurgery, Tübingen, Germany, and Center for Integrative Neuroscience, Tübingen, Germany

Locations

Center of Neurology and Hertie Institute for Clinical Brain Research, Department for Neurodegenerative Diseases and Neurosurgery University of Tübingen

Tübingen, Baden-Wurttemberg, Germany

Site Status: RECRUITING

Ludwig-Maximilians-University Munich, Klinikum Großhadern, Department for Neurology and Neurosurgery

Munich, Bavaria, Germany

Site Status: RECRUITING

University Hospital Regensburg , Department for Neurology and Neurosurgery

Regensburg, Bavaria, Germany

Site Status: RECRUITING

University Hospital Köln, Department for Neurology and Neurosurgery

Cologne, North Rhine-Westphalia, Germany

Site Status: RECRUITING

University Hospital of Düsseldorf, Departments for Neurology and Neurosurgery

Düsseldorf, North Rhine-Westphalia, Germany

Site Status: RECRUITING

University Hospital Leipzig, Department for Neurology and Neurosurgery

Leipzig, Saxony, Germany

Site Status: RECRUITING

University Hospital Kiel, Department for Neurology and Neurosurgery

Kiel, Schleswig-Holstein, Germany

Site Status: RECRUITING

Charite- University Hospital Berlin, Departments for Neurology and Neurosurgery

Berlin, , Germany

Site Status: RECRUITING

University Hospital Hamburg-Eppendorf, Department for Neurology and Neurosurgery

Hamburg, , Germany

Site Status: RECRUITING

University Hospital Luxembourg, Department for Neurology and Neurosurgery

Luxembourg, , Luxembourg

Site Status: RECRUITING

Countries

Germany; Luxembourg

Central Contacts

Daniel Weiss, MD

Role: CONTACT

daniel.weiss@uni-tuebingen.de

0049-7071-29-82340

Alireza Gharabaghi, MD

Role: CONTACT

alireza.gharabaghi@uni-tuebingen.de

0049-7071-29-83550

Facility Contacts

Daniel Weiss, MD

Role: primary

Alireza Gharabaghi, MD

Role: backup

Kai Bötzel, MD

Role: primary

Jan Mehrkens, MD

Role: backup

Josephine Blume, MD

Role: primary

Max Lange, MD

Role: backup

Michael Barbe, MD

Role: primary

Veerle Visser-Vandewalle, MD

Role: backup

Alfons Schnitzler, MD

Role: primary

Jan Vesper, MD

Role: backup

David Weise, MD

Role: primary

Dirk Winkler, MD

Role: backup

Daniela Falk, MD

Role: primary

Karsten Witt, MD

Role: backup

Andrea Kühn, MD

Role: primary

Gerd-Helge Schneider, MD

Role: backup

Monika Pötter-Nerger, MD

Role: primary

Wolfgang Hamel, MD

Role: backup

Rejko Krüger, MD

Role: primary

Frank Hertel, MD

Role: backup

References

Weiss D, Walach M, Meisner C, Fritz M, Scholten M, Breit S, Plewnia C, Bender B, Gharabaghi A, Wachter T, Kruger R. Nigral stimulation for resistant axial motor impairment in Parkinson's disease? A randomized controlled trial. Brain. 2013 Jul;136(Pt 7):2098-108. doi: 10.1093/brain/awt122. Epub 2013 Jun 11.

Reference Type: RESULT

PMID: 23757762 (View on PubMed)

Other Identifiers

IHanci

Identifier Type: -

Identifier Source: org_study_id