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

Primary Purpose

Parkinson's Disease

Status

Unknown status

Phase

Not Applicable

Locations

International

Study Type

Interventional

Intervention

[standard STN]

[STN+SNr]

About this trial

This is an interventional treatment trial for Parkinson's Disease focused on measuring Parkinson's disease, freezing of gait, deep brain stimulation, substantia nigra pars reticulata, subthalamic nucleus

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Center of Neurology and Hertie Institute for Clinical Brain Research, Department for Neurodegenerative Diseases and Neurosurgery University of TübingenRecruiting
Ludwig-Maximilians-University Munich, Klinikum Großhadern, Department for Neurology and NeurosurgeryRecruiting
University Hospital Regensburg , Department for Neurology and NeurosurgeryRecruiting
University Hospital of Düsseldorf, Departments for Neurology and NeurosurgeryRecruiting
University Hospital Köln, Department for Neurology and NeurosurgeryRecruiting
University Hospital Leipzig, Department for Neurology and NeurosurgeryRecruiting
University Hospital Kiel, Department for Neurology and NeurosurgeryRecruiting
Charite- University Hospital Berlin, Departments for Neurology and NeurosurgeryRecruiting
University Hospital Hamburg-Eppendorf, Department for Neurology and NeurosurgeryRecruiting
University Hospital Luxembourg, Department for Neurology and NeurosurgeryRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

[standard STN]

[STN+SNr]

Arm Description

Device: standard stimulation on subthalamic (STN) contacts

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

Outcomes

Primary Outcome Measures

Freezing of Gait Assessment Course (FOG-AC)

Secondary Outcome Measures

Timed Walking test from Core Assessment Program for Surgical Interventions in Parkinson's disease (CAPSIT-PD)

Berg Balance Scale

Parkinson's disease questionnaire (PDQ-39)

Freezing of gait questionnaire

Beck's depression Inventory

Columbia-Suicide Severity Rating Scale

Clinical global impression scale

Falls diary

Movement Disorders Society Unified Parkinson's disease Rating Scale (MDS-UPDRS III)

Movement Disorders Society Unified Parkinson's disease Rating Scale (MDS-UPDRS II)

Movement Disorders Society Unified Parkinson's disease Rating Scale (MDS-UPDRS IV)

Freezing of Gait Assessment Course (FOG-AC)

To determine treatment kinematics

Full Information

NCT ID

NCT02588144

First Posted

October 24, 2015

Last Updated

June 16, 2017

Sponsor

University Hospital Tuebingen

Collaborators

Medtronic

1. Study Identification

Unique Protocol Identification Number

NCT02588144

Brief Title

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

Acronym

STN+SNr

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2017

Overall Recruitment Status

Unknown status

Study Start Date

October 2015 (undefined)

Primary Completion Date

September 2017 (Anticipated)

Study Completion Date

September 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University Hospital Tuebingen

Collaborators

Medtronic

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Parkinson's Disease

Keywords

Parkinson's disease, freezing of gait, deep brain stimulation, substantia nigra pars reticulata, subthalamic nucleus

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderOutcomes Assessor

Allocation

Randomized

Enrollment

54 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

[standard STN]

Arm Type

Active Comparator

Arm Description

Device: standard stimulation on subthalamic (STN) contacts

Arm Title

[STN+SNr]

Arm Type

Experimental

Arm Description

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

Intervention Type

Procedure

Intervention Name(s)

[standard STN]

Other Intervention Name(s)

subthalamic deep brain stimulation

Intervention Description

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

Intervention Type

Procedure

Intervention Name(s)

[STN+SNr]

Other Intervention Name(s)

combined subthalamic and nigral stimulation

Intervention Description

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

Primary Outcome Measure Information:

Title

Freezing of Gait Assessment Course (FOG-AC)

Time Frame

Outcome at day 90 (V6) with reference to baseline (V1)

Secondary Outcome Measure Information:

Title

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

Title

Berg Balance Scale

Time Frame

At baseline, day 42 and 90, respectively

Title

Parkinson's disease questionnaire (PDQ-39)

Time Frame

At baseline, day 42 and 90, respectively

Title

Freezing of gait questionnaire

Time Frame

At baseline, day 42 and 90, respectively

Title

Beck's depression Inventory

Time Frame

At baseline, day 42 and 90, respectively

Title

Columbia-Suicide Severity Rating Scale

Time Frame

At baseline, day 42 and 90, respectively

Title

Clinical global impression scale

Time Frame

At day 42 and 90, respectively

Title

Falls diary

Time Frame

At baseline, day 2, 8, 21, 42 and 90, respectively

Title

Movement Disorders Society Unified Parkinson's disease Rating Scale (MDS-UPDRS III)

Time Frame

At baseline, day 2, 8, 21, 42 and 90, respectively

Title

Movement Disorders Society Unified Parkinson's disease Rating Scale (MDS-UPDRS II)

Time Frame

At baseline, day 42 and 90, respectively

Title

Movement Disorders Society Unified Parkinson's disease Rating Scale (MDS-UPDRS IV)

Time Frame

At baseline, day 42 and 90, respectively

Title

Freezing of Gait Assessment Course (FOG-AC)

Description

To determine treatment kinematics

Time Frame

At baseline, day 2, 8, 21, 42 after active treatment (STN vs. STN+SNr), respectively

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Daniel Weiss, MD

Phone

0049-7071-29-82340

daniel.weiss@uni-tuebingen.de

First Name & Middle Initial & Last Name or Official Title & Degree

Alireza Gharabaghi, MD

Phone

0049-7071-29-83550

alireza.gharabaghi@uni-tuebingen.de

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Daniel Weiss, MD

Organizational Affiliation

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

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Alireza Gharabaghi, MD

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

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

City

Tübingen

State/Province

Baden-Württemberg

ZIP/Postal Code

72076

Country

Germany

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Daniel Weiss, MD

First Name & Middle Initial & Last Name & Degree

Alireza Gharabaghi, MD

Facility Name

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

City

Munich

State/Province

Bayern

ZIP/Postal Code

81377

Country

Germany

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Kai Bötzel, MD

First Name & Middle Initial & Last Name & Degree

Jan Mehrkens, MD

Facility Name

University Hospital Regensburg , Department for Neurology and Neurosurgery

City

Regensburg

State/Province

Bayern

ZIP/Postal Code

93053

Country

Germany

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Josephine Blume, MD

First Name & Middle Initial & Last Name & Degree

Max Lange, MD

Facility Name

University Hospital of Düsseldorf, Departments for Neurology and Neurosurgery

City

Düsseldorf

State/Province

Nordrhein-Westfalen

ZIP/Postal Code

40225

Country

Germany

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Alfons Schnitzler, MD

First Name & Middle Initial & Last Name & Degree

Jan Vesper, MD

Facility Name

University Hospital Köln, Department for Neurology and Neurosurgery

City

Köln

State/Province

Nordrhein-Westfalen

ZIP/Postal Code

50924

Country

Germany

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Michael Barbe, MD

First Name & Middle Initial & Last Name & Degree

Veerle Visser-Vandewalle, MD

Facility Name

University Hospital Leipzig, Department for Neurology and Neurosurgery

City

Leipzig

State/Province

Sachsen

ZIP/Postal Code

04103

Country

Germany

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

David Weise, MD

First Name & Middle Initial & Last Name & Degree

Dirk Winkler, MD

Facility Name

University Hospital Kiel, Department for Neurology and Neurosurgery

City

Kiel

State/Province

Schleswig-Holstein

ZIP/Postal Code

24105

Country

Germany

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Daniela Falk, MD

First Name & Middle Initial & Last Name & Degree

Karsten Witt, MD

Facility Name

Charite- University Hospital Berlin, Departments for Neurology and Neurosurgery

City

Berlin

ZIP/Postal Code

10117

Country

Germany

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Andrea Kühn, MD

First Name & Middle Initial & Last Name & Degree

Gerd-Helge Schneider, MD

Facility Name

University Hospital Hamburg-Eppendorf, Department for Neurology and Neurosurgery

City

Hamburg

ZIP/Postal Code

20246

Country

Germany

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Monika Pötter-Nerger, MD

First Name & Middle Initial & Last Name & Degree

Wolfgang Hamel, MD

Facility Name

University Hospital Luxembourg, Department for Neurology and Neurosurgery

City

Luxembourg

ZIP/Postal Code

L-4362

Country

Luxembourg

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Rejko Krüger, MD

First Name & Middle Initial & Last Name & Degree

Frank Hertel, MD

12. IPD Sharing Statement

Citations:

PubMed Identifier

23757762

Citation

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.

Results Reference

result

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

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