Clinical trial NCT01355835: Combined STN/SNr-DBS for the Treatment of Refractory Gait Disorders in Parkinson's Disease
Official title: Combined STN/SNr-DBS for the Treatment of Refractory Gait Disorders in Parkinson's Disease: Design of a Two-armed Double-blind Cross-over Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson's Disease
Keywords: Parkinson's disease
gait
deep brain stimulation
substantia nigra pars reticulata
subthalamic nucleus
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
Collaborators: name: Medtronic
First posted: 2011-05-18
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 'Axial score'
timeFrame: Three weeks after active treatment (STN vs. STN+SNr), respectively
Secondary outcomes:
measure: CAPSIT-PD
timeFrame: At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively
measure: Freezing of gait assessment course
timeFrame: At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively
measure: Freezing of gait questionnaire
timeFrame: At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively
measure: Berg Balance Scale
timeFrame: At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively
measure: Non-motor symptoms scale
timeFrame: At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively
measure: Non-motor symptoms quest
timeFrame: At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively
measure: Beck's depression scale index
timeFrame: At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively
measure: Minnesota Impulsive Disorders Interview
timeFrame: At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively
measure: Barratt Impulsiveness Scale
timeFrame: At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively
measure: UPDRS I-IV
timeFrame: At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively
measure: PDQ-39
timeFrame: At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively
Other outcomes:
Locations:
city: Tübingen
country: Germany
facility: Center of Neurology and Hertie Institute for Clinical Brain Research, and Department for Neurodegenerative Diseases, University of Tübingen
state: Baden-Württemberg
Study officials:
affiliation: Center of Neurology and Hertie Institute for Clinical Brain Research, and Department for Neurodegenerative Diseases, University of Tübingen
name: Daniel Weiss, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Center of Neurology and Hertie Institute for Clinical Brain Research, and Department for Neurodegenerative Diseases, University of Tübingen
name: Rejko Krüger, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Weiss D, Breit S, Wachter T, Plewnia C, Gharabaghi A, Kruger R. Combined stimulation of the substantia nigra pars reticulata and the subthalamic nucleus is effective in hypokinetic gait disturbance in Parkinson's disease. J Neurol. 2011 Jun;258(6):1183-5. doi: 10.1007/s00415-011-5906-3. Epub 2011 Feb 2. No abstract available.
citation: Weiss D, Wachter T, Meisner C, Fritz M, Gharabaghi A, Plewnia C, Breit S, Kruger R. Combined STN/SNr-DBS for the treatment of refractory gait disturbances in Parkinson's disease: study protocol for a randomized controlled trial. Trials. 2011 Oct 11;12:222. doi: 10.1186/1745-6215-12-222.