Brain Stimulation for Patients With Parkinson Disease

Study Overview
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Brief Summary
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The aim of this crossover study is to investigate the efficacy of non-invasive brain stimulation (transcranial pulse stimulation; TPS) in adults with Parkinson Disease (PD). Participants will receive 6 sessions of TPS and Sham-TPS, respectively, in random order. Motor manifestations of PD and manual dexterity will be the primary outcome measures. Outcomes will be assessed immediately post-treatment.

Official Title
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Brain Stimulation for Patients With Parkinson Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Device: TPS (NEUROLITH)
* Device: Sham-TPS (NEUROLITH)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically stable PD with fine skilled and/or gross motor deficits (e.g. right arm with a clinical force level >2) Signed written informed consent Monthly pregnancy test for women in childbearing years Age >= 18 years Exclusion Criteria: Non-compliance with the protocol Pregnant or breastfeeding women Relevant intracerebral pathology unrelated to the disease (e.g. Brain tumor) Hemophilia or other blood clotting disorders Cortisone treatment within the last 6 weeks before first treatment Thrombosis

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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Accepts Healthy Volunteers

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1<br>TPS first with crossover to Sham-TPS | Device: TPS (NEUROLITH)<br>* 6 treatments of TPS over 2 weeks<br>Device: Sham-TPS (NEUROLITH)<br>* 6 treatments of Sham-TPS over 2 weeks<br>|
| Experimental: Sequence 2<br>Sham-TPS first with crossover to TPS | Device: TPS (NEUROLITH)<br>* 6 treatments of TPS over 2 weeks<br>Device: Sham-TPS (NEUROLITH)<br>* 6 treatments of Sham-TPS over 2 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Motor manifestations of Parkinson Disease | Motor manifestations of Parkinson Disease will be rated by an examiner using the relevant subscale (section III) of the Unified Parkinson Disease Rating Scale (UPDRS). This scale has 14 different types of ratings, with many of these ratings done independently for the different limbs (tremor at rest, action tremor, rigidity, bradykinesia, speech, facial expression, arising from a chair, posture, gait, postural stability, body bradykinesia). Each of the ratings ranges from 0 (normal) to 4 (severe manifestation). The total score for this scale ranges from 0 to 108, the sum of scores from 27 observations (Perlmutter 2009). | Immediately post-treatment | 
| Motor manifestations of Parkinson Disease | Motor manifestations of Parkinson Disease will be rated by an examiner using the relevant subscale (section III) of the Unified Parkinson Disease Rating Scale (UPDRS). This scale has 14 different types of ratings, with many of these ratings done independently for the different limbs (tremor at rest, action tremor, rigidity, bradykinesia, speech, facial expression, arising from a chair, posture, gait, postural stability, body bradykinesia). Each of the ratings ranges from 0 (normal) to 4 (severe manifestation). The total score for this scale ranges from 0 to 108, the sum of scores from 27 observations (Perlmutter 2009). | 1 month post-treatment | 
| Manual dexterity | Deficits in fine skilled movements will be assessed by the coin rotation test (Foki et al., 2010). A coin hast to be flipped with the first 3 fingers of one hand as fast as possible for 30 seconds. The number of successful half rotations will be determined. | Immediately post-treatment | 
| Manual dexterity | Deficits in fine skilled movements will be assessed by the coin rotation test (Foki et al., 2010). A coin hast to be flipped with the first 3 fingers of one hand as fast as possible for 30 seconds. The number of successful half rotations will be determined. | 1 month post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Activities of daily living (ADL) | ADL will be assessed using the relevant subscale (section II) of the UPDRS. The scale consists of 13 items (speech, salivation, swallowing, handwriting, cutting food and handling utensils, dressing, hygiene, turning in bed and adjusting bedclothes, falling (unrelated to freezing), freezing when walking, walking, tremor, sensory complaints related to parkinsonism). The scoring range for each item is from 0 (normal) to 4 (severe impairment). The examiner asks the patient to describe their function separately in the ON and OFF state. The responses for each of the items are therefore scored twice. These ratings are done by the examiner based upon the responses of the patient or caregiver. The total score for subscale 2 ranges from 0 to 56 (Perlmutter 2009). | Immediately post-treatment | 
| Activities of daily living (ADL) | ADL will be assessed using the relevant subscale (section II) of the UPDRS. The scale consists of 13 items (speech, salivation, swallowing, handwriting, cutting food and handling utensils, dressing, hygiene, turning in bed and adjusting bedclothes, falling (unrelated to freezing), freezing when walking, walking, tremor, sensory complaints related to parkinsonism). The scoring range for each item is from 0 (normal) to 4 (severe impairment). The examiner asks the patient to describe their function separately in the ON and OFF state. The responses for each of the items are therefore scored twice. These ratings are done by the examiner based upon the responses of the patient or caregiver. The total score for subscale 2 ranges from 0 to 56 (Perlmutter 2009). | 1 month post-treatment | 
| Anatomical and Functional Magnetic Resonance Imaging (3 Tesla MRI) | fMRI to analyze brain activation and connectivity. Anatomical data are also used for safety evaluations: to exclude bleeding or anatomical changes of the brain | Immediately post-treatment | 
| Somatosensory evoked EEG Potentials (SEPs) | In selected participants, standard EEG / EP (Electroencephalography / Evoked Potential) data will be recorded for procedural optimizations, i.e. evaluation of most promising parameter settings (energy level and pulse frequency). | Immediately post-stimulation | 
| Bayer Activities of Daily Living Scale (B-ADL) | The B-ADL scale is used to assess deficits in the performance of everyday activities. The scale's main target group is community dwelling patients who suffer from mild cognitive impairment or mild-to-moderate dementia. It comprises 25 items. Each item is scored from 1 (no difficulties at all) to 10 (always difficulties). The global B-ADL score is the arithmetic mean of all items. | Immediately post-treatment | 
| Bayer Activities of Daily Living Scale (B-ADL) | The B-ADL scale is used to assess deficits in the performance of everyday activities. The scale's main target group is community dwelling patients who suffer from mild cognitive impairment or mild-to-moderate dementia. It comprises 25 items. Each item is scored from 1 (no difficulties at all) to 10 (always difficulties). The global B-ADL score is the arithmetic mean of all items. | 1 month post-treatment | 
| Leisure Behavior (FZV; German: Freizeitverhalten) | The leisure behavior questionnaire has 25 items covering the following activities: information / entertainment, active movement, social interactions, creative activities, church / cultural / educational activities. The frequency of each activity is rated on a Likert-Scale from 0 (never) to 6 (daily). The total score (0-6) is calculated as the average of all 25 items. | Immediately post-treatment | 
| Leisure Behavior (FZV; German: Freizeitverhalten) | The leisure behavior questionnaire has 25 items covering the following activities: information / entertainment, active movement, social interactions, creative activities, church / cultural / educational activities. The frequency of each activity is rated on a Likert-Scale from 0 (never) to 6 (daily). The total score (0-6) is calculated as the average of all 25 items. | 1 month post-treatment | 
| Montreal Cognitive Assessment (MOCA) | The MOCA is a screening instrument for assessing cognitive impairment. It is scored out of 30 (higher scores represent better cognition) and contains sections on visuospatial/executive, naming, memory, attention, language, abstraction, and orientation. | Immediately post-treatment | 
| Montreal Cognitive Assessment (MOCA) | The MOCA is a screening instrument for assessing cognitive impairment. It is scored out of 30 (higher scores represent better cognition) and contains sections on visuospatial/executive, naming, memory, attention, language, abstraction, and orientation. | 1 month post-treatment | 
| Geriatric Depression Scale - short form (GDS-15) | he Geriatric Depression Scale (GDS) is a questionnaire to assess depression in the elderly population. This scale generates self-evaluation scores concerning various aspects with relevance for the depressive disease (e.g. mood, drive, anxiety). The short form contains 15 items. The GDS-15 score ranges from 0 (normal state) to 15 (severe depression). | Immediately post-treatment | 
| Geriatric Depression Scale - short form (GDS-15) | he Geriatric Depression Scale (GDS) is a questionnaire to assess depression in the elderly population. This scale generates self-evaluation scores concerning various aspects with relevance for the depressive disease (e.g. mood, drive, anxiety). The short form contains 15 items. The GDS-15 score ranges from 0 (normal state) to 15 (severe depression). | 1 month post-treatment | 
| Beck Depression Inventory (BDI) | BDI stands for the Beck Depression Inventory. The Beck Depression Inventory (BDI) measures the severity of depression (Beck 1961). It is a 21-item questionnaire for self-evaluation with 0-3 scores per item. The total score is the sum of all items. It ranges from 0 (normal state) to 63 (severe depression). | Immediately post-treatment | 
| Beck Depression Inventory (BDI) | BDI stands for the Beck Depression Inventory. The Beck Depression Inventory (BDI) measures the severity of depression (Beck 1961). It is a 21-item questionnaire for self-evaluation with 0-3 scores per item. The total score is the sum of all items. It ranges from 0 (normal state) to 63 (severe depression). | 1 month post-treatment |