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Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's dementia. Anxiety in PD is common, has major effects on quality of life and contributes to increased disability. The reported prevalence of anxiety in PD ranges widely and is estimated up to 40%. Treatment with oral medications is not always effective or tolerated. TMS has been shown to be effective and safe in anxiety and general anxiety disorder (GAD), but there is only limited data available for Transcranial Magnetic Stimulation (TMS) treatment of anxiety in PD. Area 8Av is a parcellation based on Human connectome project within the left prefrontal cortex and is associated with GAD. Given the area's associations with mood disorders, its functional connectivity with large-scale brain networks involved in PD, and its anatomical accessibility by TMS, this may be an important target for anxiety in PD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Theta burst stimulation | Experimental | Subjects will receive treatment with intermittent theta burst stimulation (iTBS) with the active coil. There will be a total of 27 sessions over a 3-week period with 3 sessions per day. All subjects will receive iTBS to the left 8Av region. Total participation will be 8-12 weeks. |
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| Sham device | Sham Comparator | Subjects will receive treatment with sham coil. There will be a total of 27 treatments over a 3-week period. Coil will be placed over the same region as the experimental group. Total participation will be 8-12 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Theta burst stimulation active coil | Device | MagVenture TMS Therapy active coil with theta burst stimulation. Resting motor threshold: 90%; Number of pulses per session: 1200 pulses; Inter-train interval: 8 seconds; Pulse frequency in burst: 50 Hertz; Session length: 10 min; Time between sessions: 50 minutes. |
| Measure | Description | Time Frame |
|---|---|---|
| Recruitment Rate | Percentage of participant who enroll and consent based on those contacted. A higher percentage indicates higher feasibility. | screening |
| Participation Rate | Percentage of participant who start treatment after enrollment. A higher percentage indicates higher feasibility. | 3 weeks |
| Fidelity | Percentage of participant who complete all treatment sessions. A higher percentage indicates higher fidelity. | 2 weeks |
| Completion Rate | Percentage of participant who complete 7 of the 9 treatment visits. A higher percentage indicates higher completion. | 2 weeks |
| Adverse Events Rate - Safety | Percentage of participant with adverse events. A lower percentage indicates a safer treatment. | up to 12 weeks |
| Adverse Events Safety | Frequency of each adverse event. A higher frequency indicates a less safe treatment. | up to 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Average change between baseline and 1 week post-treatment TMS vs Sham - Anxiety Scale | The Parkinson Anxiety Scale (PAS) is a 12-item scale developed to assess anxiety in individuals with Parkinson's disease (PD). Items are scored on a 5 point Likert scale. Range [0-48]. A higher score indicates higher anxiety | baseline, 1 week post-treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Explore the effect of TMS treatment on functional connectivity with Left 8 Av. - Change | Average change between baseline and 1-week post-treatment will be compared between groups (TMS vs Sham) in anomaly burden. | baseline, 1-week post treatment |
| Explore the effect of TMS treatment on functional connectivity with Left 8 Av. - Names and number of anomalous parcellations |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bhavani Kashyap, MBBS, PhD | HealthPartners Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| HealthPartners Neuroscience Center | Saint Paul | Minnesota | 55130 | United States |
No identifiable data will be shared with other researchers.
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| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| D001008 | Anxiety Disorders |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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Allocation ratio = 2:1 active intervention to sham.
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| Sham coil | Device | MagVenture TMS Therapy sham coil |
|
| Average change between baseline and 1 week post-treatment TMS vs Sham - Cognitive scale | The Montreal Cognitive Assessment (MoCA) is a brief cognitive screening measure that has been validated for use among individuals with Alzheimer's disease. The total score for this test is 30 points, but one point will be added for individuals with ≤ 12 years of education. The cutoff point for normal cognition is 26/30 in the general population and in individuals with Parkinson's Disease. This will be conducted by clinical staff and gathered as part of the chart review. Range: [0-30]. Higher score indicates higher cognitive health. | baseline, 1 week post-treatment |
| Average change between baseline and 1 week post-treatment TMS vs Sham - Mood | The Geriatric depression scale (GDS-15) short form is a screening measure for depression in older patients. Range [0-15]. A higher score indicates more depressive symptoms. | baseline, 1 week post-treatment |
| Average change between baseline and 1 week post-treatment TMS vs Sham - Motor | The United Parkinson's Disease Rating Scale (UPDRS) is the most widely used clinical rating scale for Parkinson's disease. Only part III of the rating scale is used, which is a clinician-scored monitored motor evaluation, allowing ratings from 0 (no symptoms) to 4 (severe symptoms) for each Parkinson's motor symptom. The Movement Disorders Society (MDS) commissioned a revision of the scale, resulting in a new version, termed the MDS sponsored UPDRS revision (MDS-UPDRS). In this study, the MDS-UDPRS version will be used. Range [7-86]. A higher score indicates more severe motor symptoms. | baseline, 1 week post-treatment |
| Pre-post change between baseline and 1 week post-treatment within individuals in active TMS group - Anxiety Scale | The Parkinson Anxiety Scale (PAS) is a 12-item scale developed to assess anxiety in individuals with Parkinson's disease (PD). Items are scored on a 5 point Likert scale. Range [0-48]. A higher score indicates higher anxiety | baseline, 1 week post-treatment |
| Pre-post change between baseline and 1 week post-treatment within individuals in active TMS group - Cognitive scale | The Montreal Cognitive Assessment (MoCA) is a brief cognitive screening measure that has been validated for use among individuals with Alzheimer's disease. The total score for this test is 30 points, but one point will be added for individuals with ≤ 12 years of education. The cutoff point for normal cognition is 26/30 in the general population and in individuals with Parkinson's Disease. This will be conducted by clinical staff and gathered as part of the chart review. Range: [0-30]. Higher score indicates higher cognitive health. | baseline, 1 week post-treatment |
| Pre-post change between baseline and 1 week post-treatment within individuals in active TMS group - Mood | The Geriatric depression scale (GDS-15) short form is a screening measure for depression in older patients. Range [0-15]. A higher score indicates more depressive symptoms. | baseline, 1 week post-treatment |
| Pre-post change between baseline and 1 week post-treatment within individuals in active TMS group - Motor | The United Parkinson's Disease Rating Scale (UPDRS) is the most widely used clinical rating scale for Parkinson's disease. Only part III of the rating scale is used, which is a clinician-scored monitored motor evaluation, allowing ratings from 0 (no symptoms) to 4 (severe symptoms) for each Parkinson's motor symptom. The Movement Disorders Society (MDS) commissioned a revision of the scale, resulting in a new version, termed the MDS sponsored UPDRS revision (MDS-UPDRS). In this study, the MDS-UDPRS version will be used. Range [7-86]. A higher score indicates more severe motor symptoms. | baseline, 1 week post-treatment |
| Responder Rate | Percentage of participants that respond to treatment based on improvement in symptom specific scales. Higher percentage indicates more successful treatment | baseline, 1 week post treatment |
Names and number of anomalous parcellations identified using connectivity analysis at baseline and 1-week post treatment will be described for each participant and tabulated for each arm. |
| baseline, 1-week post treatment |
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| D001523 | Mental Disorders |