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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Parkinson's Disease, Tremor

Intervention / Treatment
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* Device: Up to 3 mA, 60 us, 130 Hz deep brain stimulation
* Device: Empirical unblinded deep brain stimulation programming


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dorsal zona incerta<br>Up to 3 mA, 60 us, 130 Hz deep brain stimulation | Device: Up to 3 mA, 60 us, 130 Hz deep brain stimulation<br> <br> |
| Experimental: Caudal zona incerta<br>Up to 3 mA, 60 us, 130 Hz deep brain stimulation | Device: Up to 3 mA, 60 us, 130 Hz deep brain stimulation<br> <br> |
| Experimental: Empirical deep brain stimulation<br>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<br> <br> |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, Essential tremor, Tremor, Deep brain stimulation, Posterior subthalamic area, Zona incerta