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

Parkinson's Disease Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02588144
• Other study ID #: IHanci
• Status: Recruiting
• Phase: N/A
• First received: October 24, 2015
• Last updated: June 16, 2017
• Start date: October 2015
• Est. completion date: September 2017

Study information

• Verified date: June 2017
• Source: University Hospital Tuebingen
• Contact: Daniel Weiss, MD
• Phone: 0049-7071-29-82340
• Email: daniel.weiss[@]uni-tuebingen.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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].

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 54
• Est. completion date: September 2017
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Procedure:
• [standard STN]
High frequency deep brain stimulation with variable (best individual) stimulation on subthalamic contacts
• [STN+SNr]
high frequency deep brain stimulation of combined (best individual) subthalamic and nigral stimulation

Locations

Country	Name	City	State
Germany	Charite- University Hospital Berlin, Departments for Neurology and Neurosurgery	Berlin
Germany	University Hospital of Düsseldorf, Departments for Neurology and Neurosurgery	Düsseldorf	Nordrhein-Westfalen
Germany	University Hospital Hamburg-Eppendorf, Department for Neurology and Neurosurgery	Hamburg
Germany	University Hospital Kiel, Department for Neurology and Neurosurgery	Kiel	Schleswig-Holstein
Germany	University Hospital Köln, Department for Neurology and Neurosurgery	Köln	Nordrhein-Westfalen
Germany	University Hospital Leipzig, Department for Neurology and Neurosurgery	Leipzig	Sachsen
Germany	Ludwig-Maximilians-University Munich, Klinikum Großhadern, Department for Neurology and Neurosurgery	Munich	Bayern
Germany	University Hospital Regensburg , Department for Neurology and Neurosurgery	Regensburg	Bayern
Germany	Center of Neurology and Hertie Institute for Clinical Brain Research, Department for Neurodegenerative Diseases and Neurosurgery University of Tübingen	Tübingen	Baden-Württemberg
Luxembourg	University Hospital Luxembourg, Department for Neurology and Neurosurgery	Luxembourg

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Tuebingen	Medtronic

Countries where clinical trial is conducted

Germany,  Luxembourg, 

References & Publications (1)

Weiss D, Walach M, Meisner C, Fritz M, Scholten M, Breit S, Plewnia C, Bender B, Gharabaghi A, Wächter T, Krüger R. Nigral stimulation for resistant axial motor impairment in Parkinson's disease? A randomized controlled trial. Brain. 2013 Jul;136(Pt 7):20 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Freezing of Gait Assessment Course (FOG-AC)		Outcome at day 90 (V6) with reference to baseline (V1)
Secondary	Timed Walking test from Core Assessment Program for Surgical Interventions in Parkinson's disease (CAPSIT-PD)		At baseline, day 2, 8, 21, 42 and 90, respectively
Secondary	Berg Balance Scale		At baseline, day 42 and 90, respectively
Secondary	Parkinson's disease questionnaire (PDQ-39)		At baseline, day 42 and 90, respectively
Secondary	Freezing of gait questionnaire		At baseline, day 42 and 90, respectively
Secondary	Beck's depression Inventory		At baseline, day 42 and 90, respectively
Secondary	Columbia-Suicide Severity Rating Scale		At baseline, day 42 and 90, respectively
Secondary	Clinical global impression scale		At day 42 and 90, respectively
Secondary	Falls diary		At baseline, day 2, 8, 21, 42 and 90, respectively
Secondary	Movement Disorders Society Unified Parkinson's disease Rating Scale (MDS-UPDRS III)		At baseline, day 2, 8, 21, 42 and 90, respectively
Secondary	Movement Disorders Society Unified Parkinson's disease Rating Scale (MDS-UPDRS II)		At baseline, day 42 and 90, respectively
Secondary	Movement Disorders Society Unified Parkinson's disease Rating Scale (MDS-UPDRS IV)		At baseline, day 42 and 90, respectively
Secondary	Freezing of Gait Assessment Course (FOG-AC)	To determine treatment kinematics	At baseline, day 2, 8, 21, 42 after active treatment (STN vs. STN+SNr), respectively