Clinical trial NCT06999330: TMS in Anxiety-Parkinson's Disease
Official title: Parcel-guided Transcranial Magnetic Stimulation for Anxiety in Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Parkinsons Disease (PD)
Anxiety
Keywords: transmagnetic stimulation
functional MRI guided theta burst stimulation
intermittent theta burst stimulation
Lead sponsor: HealthPartners Institute
Sponsor class: OTHER
First posted: 2025-05-31
Enrollment: 15
Sex: ALL
Minimum age (years): 40
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Allocation ratio = 2:1 active intervention to sham.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Subject has Idiopathic PD defined by the cardinal sign, bradykinesia, plus the presence of at least 1 of the following: resting tremor or rigidity and without any other known or suspected cause of Parkinsonism (according to MDS clinical diagnostic criteria for Parkinson's disease (42) Postuma et al, Movement Disorders 2015), confirmed by a fellowship trained movements disorder specialist.
2. Subject has a diagnosis of anxiety based on PAS (Parkinson's anxiety scale) score of ≥ 14
3. Subject is Hoehn \& Yahr stage less than or equal to 3
4. Subject has a MOCA score ≥ 18
5. Subject is ≥ 40 and ≤ 90 years of age
6. Female subjects are post-menopausal or have a negative pregnancy test
7. The subject must be proficient in speaking, reading and understanding English in order to comply with procedural testing
8. Subject has provided informed written consent prior to participation. In the event that subject is legally unable to provide informed written consent due to deterioration in cognitive abilities, fully informed written consent must be provided by a legally authorized representative.
9. Subject is on a stable dose (at least 1 month prior to baseline visit) of antiparkinsonian agents and is willing to remain on this dose for the duration of the study. If the subject is on a anti-depressant or anti-anxiety medication, a stable dose without changes for 1 month is also required.

Exclusion Criteria:

1. Inability to tolerate imaging; contraindication of imaging due to implants or metal. This includes an implanted deep brain stimulation device.
2. Seizure disorder, active alcohol or substance use disorder.
3. Inability to speak and read English.
4. Anything else that, in the opinion of the PI/Clinician, would place the subject at increased risk or preclude the subject's full compliance with or completion of the study.
5. Subject has atypical Parkinson's syndrome(s) due to drugs (e.g., metoclopramide, neuroleptics), metabolic neurogenetic disorders (e.g., Wilson's Disease), encephalitis, cerebrovascular disease, or degenerative disease (e.g., Progressive Supranuclear Palsy, Multiple System Atrophy, Corticobasal Degeneration, Lewy Body dementia)
6. Other forms of advanced dementia (PDD, AD), or MOCA \<18
7. Subject has history of any of the following: moderate to severe pulmonary disease, poorly controlled congestive heart failure, significant cardiovascular and/or cerebrovascular events within previous 6 months, or any other clinically relevant abnormality that inclusion would pose a safety risk to the subject as determined by investigator.
8. Subject has history of any psychiatric illness that would pose a safety risk to the subject as determined by investigator.
9. Subject is currently taking sedative medications that are clinically contraindicated as determined by investigator.
10. Subject has undergone a recent change (\<1 month) in their anti-parkinsonian medication, or anti-depressant medication or anti-anxiety medication at the baseline visit.
11. Safety risk to the subject as determined by investigator.
12. Subject has participated in a clinical trial investigation within 3 months of this study

Primary outcomes:
measure: Recruitment Rate
timeFrame: screening
measure: Participation Rate
timeFrame: 3 weeks
measure: Fidelity
timeFrame: 2 weeks
measure: Completion Rate
timeFrame: 2 weeks
measure: Adverse Events Rate - Safety
timeFrame: up to 12 weeks
measure: Adverse Events Safety
timeFrame: up to 12 weeks
Secondary outcomes:
measure: Average change between baseline and 1 week post-treatment TMS vs Sham - Anxiety Scale
timeFrame: baseline, 1 week post-treatment
measure: Average change between baseline and 1 week post-treatment TMS vs Sham - Cognitive scale
timeFrame: baseline, 1 week post-treatment
measure: Average change between baseline and 1 week post-treatment TMS vs Sham - Mood
timeFrame: baseline, 1 week post-treatment
measure: Average change between baseline and 1 week post-treatment TMS vs Sham - Motor
timeFrame: baseline, 1 week post-treatment
measure: Pre-post change between baseline and 1 week post-treatment within individuals in active TMS group - Anxiety Scale
timeFrame: baseline, 1 week post-treatment
measure: Pre-post change between baseline and 1 week post-treatment within individuals in active TMS group - Cognitive scale
timeFrame: baseline, 1 week post-treatment
measure: Pre-post change between baseline and 1 week post-treatment within individuals in active TMS group - Mood
timeFrame: baseline, 1 week post-treatment
measure: Pre-post change between baseline and 1 week post-treatment within individuals in active TMS group - Motor
timeFrame: baseline, 1 week post-treatment
measure: Responder Rate
timeFrame: baseline, 1 week post treatment
Other outcomes:
measure: Explore the effect of TMS treatment on functional connectivity with Left 8 Av. - Change
timeFrame: baseline, 1-week post treatment
measure: Explore the effect of TMS treatment on functional connectivity with Left 8 Av. - Names and number of anomalous parcellations
timeFrame: baseline, 1-week post treatment
Locations:
city: Saint Paul
country: United States
facility: HealthPartners Neuroscience Center
state: Minnesota
Study officials:
affiliation: HealthPartners Institute
name: Bhavani Kashyap, MBBS, PhD
role: PRINCIPAL_INVESTIGATOR
References: