Randomised Crossover Trial of DBS of Differential PSA Regions in Parkinson's Disease and Tremor

Randomised Crossover Trial of Deep Brain Stimulation of Differential Posterior Subthalamic Area Regions in Parkinson's Disease and Tremor

The posterior subthalamic area holds promise as a target region for deep brain stimulation in tremor and Parkinson's disease. Using the magnetic resonance-directed implantable guide tube surgical technique, subregions of the posterior subthalamic area can be individually targetted on a single electrode lead trajectory. The hypothesis is that the caudal zona incerta may provide improved control of movement disorder symptoms than the more commonly stimulated dorsal zona incerta.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease; Tremor
• Intervention / Treatment: Device: Up to 3 mA, 60 us, 130 Hz deep brain stimulation; Device: Empirical unblinded deep brain stimulation programming

Detailed Description

Randomisation between two treatment locations each programmed up to 3 milliamps in amplitude for 3 months: (1) caudal zona incerta and (2) dorsal zona incerta. This 6-month-long randomised phase is followed by 6 months of unblinded individualised empirically optimised settings programmed by a neurologist. Each of the three treatment periods ends with a full clinical, functional and quality of life assessment.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Medication-refractory tremor and/or Parkinson's disease as defined by UK Brain Bank criteria with either inadequate control of motor fluctuations or dyskinesia despite optimised medical therapy

Exclusion Criteria:

• Significant cognitive, psychiatric and medical co-morbidities
• Dementia with mini mental state examination score of less than 25/30
• Limited life expectancy due to a co-morbid condition

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dorsal zona incerta; Up to 3 mA, 60 us, 130 Hz deep brain stimulation	Device: Up to 3 mA, 60 us, 130 Hz deep brain stimulation
EXPERIMENTAL: Caudal zona incerta; Up to 3 mA, 60 us, 130 Hz deep brain stimulation	Device: Up to 3 mA, 60 us, 130 Hz deep brain stimulation
EXPERIMENTAL: Empirical deep brain stimulation; Empirical unblinded deep brain stimulation programming using any posterior subthalamic area electrode contact(s) and stimulation parameters to optimise clinical outcome.	Device: Empirical unblinded deep brain stimulation programming

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline United Parkinsons Disease Rating Scale Part III at 3 months	At end of first randomised crossover trial period	3 months
Change from baseline United Parkinsons Disease Rating Scale Part III at 6 months	At end of second randomised crossover trial period	6 months
Change from baseline United Parkinsons Disease Rating Scale Part III at 12 months	At end of non-randomised empirical deep brain stimulator programming period	12 months
Change from baseline Fahn Tolosa Marin tremor scale at 3 months	At end of first randomised crossover trial period for tremor patients	3 months
Change from baseline Fahn Tolosa Marin tremor scale at 6 months	At end of second randomised crossover trial period for tremor patients	6 months
Change from baseline Fahn Tolosa Marin tremor scale at 12 months	At end of empirical deep brain stimulator programming period for tremor patients	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline ON-OFF diary at 3 months	For Parkinson's disease	3 months
Change from baseline ON-OFF diary at 6 months	For Parkinson's disease	6 months
Change from baseline ON-OFF diary at 12 months	For Parkinson's disease	12 months
Adverse events	Any adverse medical event from date of randomization until the date of first documented adverse event or date of death from any cause, whichever came first, assessed up to 12 months	12 months
Change from baseline Short form 36 at 3 months	At end of first randomised crossover period	3 months
Change from baseline Short form 36 at 6 months	At end of second randomised crossover period	6 months
Change from baseline Short form 36 at 12 months	At end of empirical deep brain stimulator programming period	12 months
Change from baseline Parkinsons Disease Quality of Life 39 at 3 months	At end of first randomised crossover period for Parkinsons disease	3 months
Change from baseline Parkinsons Disease Quality of Life 39 at 6 months	At end of second randomised crossover period for Parkinsons disease	6 months
Change from baseline Parkinsons Disease Quality of Life 39 at 12 months	At end of empirical deep brain stimulator programming period for Parkinsons disease	12 months
Change from baseline L-dopa equivalent dose at 3 months	At end of first randomised crossover period for Parkinsons disease	3 months
Change from baseline L-dopa equivalent dose at 6 months	At end of second randomised crossover period for Parkinsons disease	3 months
Change from baseline L-dopa equivalent dose at 12 months	At end of empirical deep brain stimulator programming period for Parkinsons disease	12 months
Change from baseline neuropsychological battery at 3 months	At end of first randomised crossover period	3 months
Change from baseline neuropsychological battery at 6 months	At end of second randomised crossover period	6 months
Change from baseline neuropsychological battery at 12 months	At end of empirical deep brain stimulator programming period	12 months
Change from baseline verbal fluency at 3 months	At end of first randomised crossover period	3 months
Change from baseline verbal fluency at 6 months	At end of second randomised crossover period	6 months
Change from baseline verbal fluency at 12 months	At end of empirical deep brain stimulator programming period	12 months
Change from baseline Mini-International Neuropsychiatric Interview Plus at 3 months	At end of first randomised crossover period	3 months
Change from baseline Mini-International Neuropsychiatric Interview Plus at 6 months	At end of second randomised crossover period	6 months
Change from baseline Mini-International Neuropsychiatric Interview Plus at 12 months	At end of empirical deep brain stimulator programming period	12 months
Change from baseline United Parkinsons Disease Rating Scale parts I, II, IV, V at 3 months	At end of first randomised crossover period for Parkinsons disease	3 months
Change from baseline United Parkinsons Disease Rating Scale parts I, II, IV, V at 6 months	At end of second randomised crossover period for Parkinsons disease	6 months
Change from baseline United Parkinsons Disease Rating Scale parts I, II, IV, V at 12 months	At end of empirical deep brain stimulator programming period for Parkinsons disease	12 months
Change from baseline Abnormal Involuntary Movement Scale at 3 months	At end of first randomised crossover period for Parkinsons disease	3 months
Change from baseline Abnormal Involuntary Movement Scale at 6 months	At end of second randomised crossover period for Parkinsons disease	6 months
Change from baseline Abnormal Involuntary Movement Scale at 12 months	At end of empirical deep brain stimulator programming period for Parkinsons disease	12 months

Collaborators and Investigators

• Sponsor: The University of Western Australia
• Investigators: Principal Investigator: Christopher Lind, MBChB, FRACS, The University of Western Australia

Publications and helpful links

Helpful Links

• Surgical NeuroDiscovery Group

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2012
• Primary Completion (ACTUAL): August 30, 2019
• Study Completion (ACTUAL): August 30, 2020

Study Registration Dates

• First Submitted: September 14, 2013
• First Submitted That Met QC Criteria: September 14, 2013
• First Posted (ESTIMATE): September 18, 2013

Study Record Updates

• Last Update Posted (ACTUAL): May 18, 2021
• Last Update Submitted That Met QC Criteria: May 13, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Parkinson's disease; Essential tremor; Tremor; Deep brain stimulation; Posterior subthalamic area; Zona incerta
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dyskinesias; Parkinson Disease; Tremor
• Other Study ID Numbers: 2012-039