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

This study has been completed.
Sponsor:
Collaborator:
Medtronic
Information provided by (Responsible Party):
Daniel Weiss, University Hospital Tuebingen
ClinicalTrials.gov Identifier:
NCT01355835
First received: May 13, 2011
Last updated: August 7, 2012
Last verified: August 2012
History of Changes
  Purpose

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].


Condition Intervention Phase
Parkinson's Disease
 Device: deep brain stimulation (ACTIVA PC, Medtronic)
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University Hospital Tuebingen:

Primary Outcome Measures:
  • 'Axial score' [ Time Frame: Three weeks after active treatment (STN vs. STN+SNr), respectively ] [ Designated as safety issue: Yes ]

    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:
  • CAPSIT-PD [ Time Frame: At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively ] [ Designated as safety issue: No ]
  • Freezing of gait assessment course [ Time Frame: At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively ] [ Designated as safety issue: No ]
  • Freezing of gait questionnaire [ Time Frame: At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively ] [ Designated as safety issue: No ]
  • Berg Balance Scale [ Time Frame: At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively ] [ Designated as safety issue: No ]
  • Non-motor symptoms scale [ Time Frame: At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively ] [ Designated as safety issue: No ]
  • Non-motor symptoms quest [ Time Frame: At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively ] [ Designated as safety issue: No ]
  • Beck's depression scale index [ Time Frame: At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively ] [ Designated as safety issue: Yes ]
  • Minnesota Impulsive Disorders Interview [ Time Frame: At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively ] [ Designated as safety issue: No ]
  • Barratt Impulsiveness Scale [ Time Frame: At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively ] [ Designated as safety issue: Yes ]
  • UPDRS I-IV [ Time Frame: At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively ] [ Designated as safety issue: Yes ]
  • PDQ-39 [ Time Frame: At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: February 2011
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: [STNmono]
Conventional stimulation on subthalamic contacts
 Device: deep brain stimulation (ACTIVA PC, Medtronic)
High frequent deep brain stimulation with variable (best individual) stimulation on subthalamic contacts and standard parameters on nigral contacts (125 Hz, 60µs, best individual amplitude)
Other Name: Neurostimulation with ACTIVA PC, Medtronic
Experimental: [STN+SNr]
Combined subthalamic and nigral stimulation
 Device: deep brain stimulation (ACTIVA PC, Medtronic)
High frequent deep brain stimulation with variable (best individual) stimulation on subthalamic contacts and standard parameters on nigral contacts (125 Hz, 60µs, best individual amplitude)
Other Name: Neurostimulation with ACTIVA PC, Medtronic

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01355835

Locations
Germany
Center of Neurology and Hertie Institute for Clinical Brain Research, and Department for Neurodegenerative Diseases, University of Tübingen
Tübingen, Baden-Württemberg, Germany, 72076
Sponsors and Collaborators
University Hospital Tuebingen
Medtronic
Investigators
Principal Investigator: Daniel Weiss, MD Center of Neurology and Hertie Institute for Clinical Brain Research, and Department for Neurodegenerative Diseases, University of Tübingen
Principal Investigator: Rejko Krüger, MD Center of Neurology and Hertie Institute for Clinical Brain Research, and Department for Neurodegenerative Diseases, University of Tübingen
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Daniel Weiss, MD, University Hospital Tuebingen
ClinicalTrials.gov Identifier: NCT01355835     History of Changes
Other Study ID Numbers: AKF 259-0-0
Study First Received: May 13, 2011
Last Updated: August 7, 2012
Health Authority: Germany: Ethics Commission

Keywords provided by University Hospital Tuebingen:
Parkinson's disease
gait
deep brain stimulation
substantia nigra pars reticulata
subthalamic nucleus

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
 Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases

ClinicalTrials.gov processed this record on May 21, 2013