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

Parkinson's Disease Clinical Trial

— STN/SNr  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01355835
• Other study ID #: AKF 259-0-0
• Status: Completed
• Phase: Phase 2
• First received: May 13, 2011
• Last updated: August 7, 2012
• Start date: February 2011
• Est. completion date: August 2012

Study information

• Verified date: August 2012
• Source: University Hospital Tuebingen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Interventional

Clinical Trial 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].

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 information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

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)

Locations

Country	Name	City	State
Germany	Center of Neurology and Hertie Institute for Clinical Brain Research, and Department for Neurodegenerative Diseases, University of Tübingen	Tübingen	Baden-Württemberg

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Tuebingen	Medtronic

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Weiss D, Breit S, Wächter T, Plewnia C, Gharabaghi A, Krüger 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	'Axial score'	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	Three weeks after active treatment (STN vs. STN+SNr), respectively	Yes
Secondary	CAPSIT-PD		At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively	No
Secondary	Freezing of gait assessment course		At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively	No
Secondary	Freezing of gait questionnaire		At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively	No
Secondary	Berg Balance Scale		At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively	No
Secondary	Non-motor symptoms scale		At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively	No
Secondary	Non-motor symptoms quest		At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively	No
Secondary	Beck's depression scale index		At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively	Yes
Secondary	Minnesota Impulsive Disorders Interview		At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively	No
Secondary	Barratt Impulsiveness Scale		At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively	Yes
Secondary	UPDRS I-IV		At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively	Yes
Secondary	PDQ-39		At baseline and three weeks after active treatment (STN vs. STN+SNr), respectively	No