rTMS Pilot for Anxiety

Open-label Pilot to Test a Novel 1 Hz Intensive Repetitive Transcranial Magnetic Stimulation Paradigm in Patients With Anxiety

The purpose of this study is to evaluate the safety and tolerability of 1 Hz parietal stimulation in anxiety. Our approach will be to administer 1 week of open-label accelerated 1 Hz parietal rTMS (5 days, 8 sessions/day, 600 pulses/session) and measure the effect of this neuromodulation on APS, and short term memory in a cohort of anxiety GAD patients.

Study Overview

• Status: Terminated
• Conditions: Generalized Anxiety Disorder
• Intervention / Treatment: Device: Open-label accelerated 1 Hz repetitive transcranial magnetic stimulation

Detailed Description

Aims 1 and 2 of this project will be tested using a within-subjects design where anxiety patients will receive a 5-day course of accelerated 1 Hz rTMS (8x session x 600 pulses/session) to the right IPS. In Aim 1, we will test the effects of this stimulation on arousal during the NPU threat task (NPU section). In Aim 2 below, we will test the effects of this stimulation on arousal-related attention control deficits using the VSTM task (VSTM section).

Subjects will undergo 7 study visits spaced over a roughly 3-week period depending upon availability. First, subjects will have a pre-stimulation test visit. On this visit they will undergo the following procedures: 1) motor threshold testing, 2) noise habituation, 3) shock workup 4) NPU task, 5) VSTM task. Then they will have 5 rTMS visits. On these visits, subjects will receive 8 trains of 1 Hz rTMS (600 pulses per train, each separated by ~50 min). Finally, they will have a post-stimulation test visit, which will included the noise habituation, shock workup, NPU task, and VSTM task.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nicholas L Balderston; Phone Number: 2157463058; Email: nicholas.balderston@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Meet the DSM-V criteria for an anxiety disorder (i.e. generalized anxiety disorder, social anxiety disorder, panic disorder, etc.)
• Subjects must be 18-50 years old
• Able to give their consent
• Right-handed

Exclusion Criteria

• Non-english speaking
• Any significant medical or neurological problems
• Current or past (non-anxiety) Axis I psychiatric disorder(s), active or history of active suicidal ideation
• Alcohol/drug problems in the past year or lifetime alcohol or drug dependence
• Any medical condition that increases risk for TMS
• History of seizure
• History of epilepsy
• Increased risk of seizure for any reason
• Pregnancy, or positive pregnancy test
• Hearing loss

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Pilot arm; Aims 1 and 2 of this project will be tested using a within-subjects design where anxiety patients will receive a 5-day course of accelerated 1 Hz rTMS (8x session x 600 pulses/session) to the right IPS.	Device: Open-label accelerated 1 Hz repetitive transcranial magnetic stimulation; Patients will receive a 5-day course of accelerated 1 Hz rTMS (8x session x 600 pulses/session) to the right intraparietal sulcus. Subjects will receive a continuous train of 1 Hz stimulation. They will receive a total of 600 pulses per train. Trains will be separated by ~50 min rest intervals.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anxiety Potentiated Startle (APS)	Electromyography (EMG) startle responses were recorded from the left orbicularis oculi muscle using a Biopac MP160 unit (Biopac; Goleta, CA) via 15 × 20 mm electrodes (Rhythmlink #DECUS10026; Columbia, SC). EMG was bandpass filtered from 30 to 300 Hz, rectified, and smoothed using a 20-ms sliding window. Startle responses were scored as the peak (max during the 20 ms to 120 ms post-noise window) - the baseline (50 ms pre-noise window), and converted to t-scores with a mean of 50 and a standard deviation of 10 (tx = [Zx × 10] + 50). Greater t-scores mean larger blinks, which could be associated with greater anxiety, however there is no clinically relevent threshold. Noisy trials (baseline SD > 2x run SD) were excluded, and "no blink" (peak < baseline range) trials were coded as 0. To calculate APS within each timepoint, we subtracted the response during the neutral ITI from the response during the unpredictable ITI. T-scores represent the change from baseline to post stimulation.	Post stimulation
Visual Short Term Memory Performance (VSTM)	Visual short term memory task: This task has been adapted from Vogel & Machizawa (Vogel & Machizawa, 2004). On each trial, subjects see an arrow (cue) pointing to the left or the right. After a short delay, they see a bilateral array of squares that vary in color, location, and angle of rotation (memory array). Subjects are instructed to encode the squares in the cued hemifield (targets) and ignore the squares contralateral to the cued hemifield (distractors). After another short delay (retention interval), subjects see a single square (response prompt) that is either an exact match (same color/location/angle) or a complete mismatch (different color/location/angle). Subjects are instructed to indicate whether the square is a match or a mismatch.	Pre and post stimulation

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Nicholas L Balderston, University of Pennsylvania

Publications and helpful links

General Publications

• Balderston NL, Beydler EM, Goodwin M, Deng ZD, Radman T, Luber B, Lisanby SH, Ernst M, Grillon C. Low-frequency parietal repetitive transcranial magnetic stimulation reduces fear and anxiety. Transl Psychiatry. 2020 Feb 17;10(1):68. doi: 10.1038/s41398-020-0751-8.

Helpful Links

• Online Screening Form

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2022
• Primary Completion (Actual): August 1, 2022
• Study Completion (Actual): August 1, 2022

Study Registration Dates

• First Submitted: March 23, 2022
• First Submitted That Met QC Criteria: March 31, 2022
• First Posted (Actual): April 1, 2022

Study Record Updates

• Last Update Posted (Actual): April 21, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders
• Other Study ID Numbers: 850766

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will not be shared with other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No