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

June 16, 2017 updated by: Daniel Weiss, University Hospital Tuebingen

Combined Stimulation of Subthalamic Nucleus and Substantia Nigra Pars Reticulata for Resistant Freezing of Gait in Parkinson's Disease: A Randomized Controlled Multicenter Trial

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].

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

54

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Berlin, Germany, 10117
        • Recruiting
        • Charite- University Hospital Berlin, Departments for Neurology and Neurosurgery
        • Contact:
          • Andrea Kühn, MD
        • Contact:
          • Gerd-Helge Schneider, MD
      • Hamburg, Germany, 20246
        • Recruiting
        • University Hospital Hamburg-Eppendorf, Department for Neurology and Neurosurgery
        • Contact:
          • Monika Pötter-Nerger, MD
        • Contact:
          • Wolfgang Hamel, MD
    • Baden-Württemberg
      • Tübingen, Baden-Württemberg, Germany, 72076
        • Recruiting
        • Center of Neurology and Hertie Institute for Clinical Brain Research, Department for Neurodegenerative Diseases and Neurosurgery University of Tübingen
        • Contact:
          • Daniel Weiss, MD
        • Contact:
          • Alireza Gharabaghi, MD
    • Bayern
      • Munich, Bayern, Germany, 81377
        • Recruiting
        • Ludwig-Maximilians-University Munich, Klinikum Großhadern, Department for Neurology and Neurosurgery
        • Contact:
          • Kai Bötzel, MD
        • Contact:
          • Jan Mehrkens, MD
      • Regensburg, Bayern, Germany, 93053
        • Recruiting
        • University Hospital Regensburg , Department for Neurology and Neurosurgery
        • Contact:
          • Josephine Blume, MD
        • Contact:
          • Max Lange, MD
    • Nordrhein-Westfalen
      • Düsseldorf, Nordrhein-Westfalen, Germany, 40225
        • Recruiting
        • University Hospital of Düsseldorf, Departments for Neurology and Neurosurgery
        • Contact:
          • Alfons Schnitzler, MD
        • Contact:
          • Jan Vesper, MD
      • Köln, Nordrhein-Westfalen, Germany, 50924
        • Recruiting
        • University Hospital Köln, Department for Neurology and Neurosurgery
        • Contact:
          • Michael Barbe, MD
        • Contact:
          • Veerle Visser-Vandewalle, MD
    • Sachsen
      • Leipzig, Sachsen, Germany, 04103
        • Recruiting
        • University Hospital Leipzig, Department for Neurology and Neurosurgery
        • Contact:
          • David Weise, MD
        • Contact:
          • Dirk Winkler, MD
    • Schleswig-Holstein
      • Kiel, Schleswig-Holstein, Germany, 24105
        • Recruiting
        • University Hospital Kiel, Department for Neurology and Neurosurgery
        • Contact:
          • Karsten Witt, MD
        • Contact:
          • Daniela Falk, MD
  • Luxembourg
      • Luxembourg, Luxembourg, L-4362
        • Recruiting
        • University Hospital Luxembourg, Department for Neurology and Neurosurgery
        • Contact:
          • Rejko Krüger, MD
        • Contact:
          • Frank Hertel, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: [standard STN]
Device: standard stimulation on subthalamic (STN) contacts
Procedure: [standard STN]
High frequency deep brain stimulation with variable (best individual) stimulation on subthalamic contacts
Other Names:
  • subthalamic deep brain stimulation
Experimental: [STN+SNr]
Device: Combined stimulation of the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr)
Procedure: [STN+SNr]
high frequency deep brain stimulation of combined (best individual) subthalamic and nigral stimulation
Other Names:
  • combined subthalamic and nigral stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Freezing of Gait Assessment Course (FOG-AC)
Time Frame: Outcome at day 90 (V6) with reference to baseline (V1)
Outcome at day 90 (V6) with reference to baseline (V1)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Timed Walking test from Core Assessment Program for Surgical Interventions in Parkinson's disease (CAPSIT-PD)
Time Frame: At baseline, day 2, 8, 21, 42 and 90, respectively
At baseline, day 2, 8, 21, 42 and 90, respectively
Berg Balance Scale
Time Frame: At baseline, day 42 and 90, respectively
At baseline, day 42 and 90, respectively
Parkinson's disease questionnaire (PDQ-39)
Time Frame: At baseline, day 42 and 90, respectively
At baseline, day 42 and 90, respectively
Freezing of gait questionnaire
Time Frame: At baseline, day 42 and 90, respectively
At baseline, day 42 and 90, respectively
Beck's depression Inventory
Time Frame: At baseline, day 42 and 90, respectively
At baseline, day 42 and 90, respectively
Columbia-Suicide Severity Rating Scale
Time Frame: At baseline, day 42 and 90, respectively
At baseline, day 42 and 90, respectively
Clinical global impression scale
Time Frame: At day 42 and 90, respectively
At day 42 and 90, respectively
Falls diary
Time Frame: At baseline, day 2, 8, 21, 42 and 90, respectively
At baseline, day 2, 8, 21, 42 and 90, respectively
Movement Disorders Society Unified Parkinson's disease Rating Scale (MDS-UPDRS III)
Time Frame: At baseline, day 2, 8, 21, 42 and 90, respectively
At baseline, day 2, 8, 21, 42 and 90, respectively
Movement Disorders Society Unified Parkinson's disease Rating Scale (MDS-UPDRS II)
Time Frame: At baseline, day 42 and 90, respectively
At baseline, day 42 and 90, respectively
Movement Disorders Society Unified Parkinson's disease Rating Scale (MDS-UPDRS IV)
Time Frame: At baseline, day 42 and 90, respectively
At baseline, day 42 and 90, respectively
Freezing of Gait Assessment Course (FOG-AC)
Time Frame: At baseline, day 2, 8, 21, 42 after active treatment (STN vs. STN+SNr), respectively
To determine treatment kinematics
At baseline, day 2, 8, 21, 42 after active treatment (STN vs. STN+SNr), respectively

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Tuebingen

Collaborators

Medtronic

Investigators

  • Principal Investigator: Daniel Weiss, MD, Department for Neurodegenerative Diseases, Centre for Neurology, Tübingen, Germany, and Hertie-Institute for Clinical Brain Research
  • Principal Investigator: Alireza Gharabaghi, MD, Division of Functional and Restorative Neurosurgery, Department of Neurosurgery, Tübingen, Germany, and Center for Integrative Neuroscience, Tübingen, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2015

Primary Completion (Anticipated)

September 1, 2017

Study Completion (Anticipated)

September 1, 2017

Study Registration Dates

First Submitted

October 24, 2015

First Submitted That Met QC Criteria

October 24, 2015

First Posted (Estimate)

October 27, 2015

Study Record Updates

Last Update Posted (Actual)

June 20, 2017

Last Update Submitted That Met QC Criteria

June 16, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IHanci

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Parkinson's Disease

Clinical Trials on [standard STN]

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Germany

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe