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

University Hospital Tuebingen

Status: Unknown

Conditions: Parkinson's Disease

Treatments: Procedure: [STN+SNr]; Procedure: [standard STN]

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02588144

IHanci

Details and patient eligibility

About

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].

Full 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.

Enrollment: 54 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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54 participants in 2 patient groups

[standard STN]

Active Comparator group

Description:

Device: standard stimulation on subthalamic (STN) contacts

Treatment:

Procedure: [standard STN]

[STN+SNr]

Experimental group

Description:

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

Treatment:

Procedure: [STN+SNr]