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Combined STN/SNr-DBS for the Treatment of Refractory Gait Disorders in Parkinson's Disease

Phase 2
Completed
Conditions
Parkinson's Disease
Interventions
Device: deep brain stimulation (ACTIVA PC, Medtronic)
Registration Number
NCT01355835
Lead Sponsor
University Hospital Tuebingen
Brief Summary

12 patients with idiopathic Parkinson's disease and refractory gait disturbances under best individual subthalamic nucleus stimulation and dopaminergic medication will be included into this randomised double-blind cross-over two-armed clinical trial. The treatment consists of two different stimulation settings using (i) conventional stimulation of the subthalamic nucleus \[STNmono\] and (ii) combined stimulation of distant electrode contacts located in the subthalamic nucleus and caudal border zone of STN and substantia nigra pars reticulata \[STN+SNr\].

Detailed Description

A composite 'axial score' including the major clinical and anamnestic items on gait, posture and balance function from UPDRSII (items 13-15) and UPDRS III (items 27-31) constitutes the primary outcome measure. Secondary outcome measures include specified clinical and anamnestic assessments on freezing of gait, balance, quality of life, non-motor symptoms, impulsivity, impulse control and neuropsychiatric symptoms. The aim of the present trial is to investigate the efficacy and safety of combined stimulation on subthalamic and nigral electrode contacts \[STN+SNr\] in refractory hypokinetic gait disturbances compared with \[STNmono\] (active comparator). The results will clarify, whether the combined \[STN+SNr\] stimulation improves otherwise refractory gait disturbances in PD.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
12
Inclusion Criteria
  • Written informed consent
  • Age: between 18 and 80 years
  • Idiopathic Parkinson's disease (according to the "British Brain Bank criteria" (Hughes, 1992) including genetic forms and therapy with STN-DBS (ACTIVA pulse generators) at least six months from surgery
  • Optimized subthalamic stimulation at study enrolment (refer 'treatment' section)
  • Gait disturbance refractory on best individual STN-DBS (STNmono) and dopaminergic therapy: 'gait score' in the best clinical [MedOn/STNmono] condition ≥ 12
  • Clinical and image-guided (and facultatively electrophysiological) confirmation of (i) one of the two rostral contacts of the quadripolar electrode localized in the STN area, and (ii) the caudal contacts in the border zone of STN and SNr.
  • Dopaminergic medication constant for at least four weeks prior to study enrolment
  • Disease duration ≥ 5 years
Exclusion Criteria
  • Cognitive impairment (Mini Mental State Exam < 25)
  • Participation in other clinical trials within the past three months and during enrolment in our study
  • Suicidality, Psychosis
  • Other severe pathological chronic condition that might confound treatment effects or interpretation of the data
  • Pregnancy
  • Acute adverse events from stimulation on contacts in the caudal STN / SNr border interfering with the intended stimulation protocol

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
[STNmono]deep brain stimulation (ACTIVA PC, Medtronic)Conventional stimulation on subthalamic contacts
[STN+SNr]deep brain stimulation (ACTIVA PC, Medtronic)Combined subthalamic and nigral stimulation
Primary Outcome Measures
NameTimeMethod
'Axial score'Three weeks after active treatment (STN vs. STN+SNr), respectively

The composite 'axial score' is built by 8 items from the UPDRS II and III, all 5-point rated (0 to 4) representing increasing levels of pathology. The 'axial score' will be scored by the sum of the ratings across the 8 items (Range 0 to 32). As change in UPDRS scores is a common primary efficacy outcome measure in Parkinson's disease and only items of the original UPDRS are required for the definition of the primary endpoint, the statistical evaluation methods should be based on the psychometric validation of the UPDRS and no own validation studies are necessary.

Safety: falls

Secondary Outcome Measures
NameTimeMethod
CAPSIT-PDAt baseline and three weeks after active treatment (STN vs. STN+SNr), respectively
Freezing of gait assessment courseAt baseline and three weeks after active treatment (STN vs. STN+SNr), respectively
Freezing of gait questionnaireAt baseline and three weeks after active treatment (STN vs. STN+SNr), respectively
Berg Balance ScaleAt baseline and three weeks after active treatment (STN vs. STN+SNr), respectively
Non-motor symptoms scaleAt baseline and three weeks after active treatment (STN vs. STN+SNr), respectively
Non-motor symptoms questAt baseline and three weeks after active treatment (STN vs. STN+SNr), respectively
Beck's depression scale indexAt baseline and three weeks after active treatment (STN vs. STN+SNr), respectively
Minnesota Impulsive Disorders InterviewAt baseline and three weeks after active treatment (STN vs. STN+SNr), respectively
Barratt Impulsiveness ScaleAt baseline and three weeks after active treatment (STN vs. STN+SNr), respectively
UPDRS I-IVAt baseline and three weeks after active treatment (STN vs. STN+SNr), respectively
PDQ-39At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively

Trial Locations

Locations (1)

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

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Tübingen, Baden-Württemberg, Germany

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