Modulating Anxious Coping

Modeling and Modulating Mechanisms of Escape, Avoidance, and Approach in the Anxiety Disorder Spectrum

This is a study to find out if a device that temporarily alters brain activity (repetitive transcranial magnetic stimulation, rTMS) might be used to change how people with anxiety or related concerns cope with feared or anxiety-producing situations. The study is recruiting people who recently started treatment for anxiety or a related concern. The study involves 3 visits to the Medical University of South Carolina. At the first visit, participants do interviews and surveys asking about anxiety and related concerns, and they also do tasks where they see and react to emotional pictures while their brain activation is measured. At the next two visits, participants receive rTMS, which works by rapidly turning a focused magnetic field on and off repeatedly over the head in a way that passes directly through the hair, scalp, and skull and onto the brain and can temporarily increase brain activity under the magnetic field. After rTMS, participants do two tasks where they see and react to emotional situations while wearing sensors on their hand, arms, face, and head.

Each visit in this study is expected to last between 2 - 4 hours. This is not a treatment study, but the study is being conducted with the hope that it will help improve treatment in the future.

Study Overview

• Status: Recruiting
• Conditions: Anxiety Disorders
• Intervention / Treatment: Device: Repetitive Transcranial Magnetic Stimulation (rTMS)

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christopher T Sege, PhD; Phone Number: 8437928465; Email: sege@musc.edu

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Contact: Christopher T Sege; Phone Number: 978-764-1480; Email: sege@musc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 - 65 y.o.
• Meets criteria for an anxiety disorder (Generalized Anxiety Disorder, Panic Disorder, Social Anxiety Disorder, Specific Phobia), posttraumatic stress disorder, obsessive- compulsive disorder, or current adjustment disorder with anxiety
• Is currently seeking mental health treatment
• Is able to read consent document and provide informed consent.
• English is a first or primary fluent language.

Exclusion Criteria:

• Current alcohol or substance use disorder of more than mild severity (as defined by DSM-5 and determined using standardized self-report instruments)
• Lifetime diagnosis of psychotic disorder or bipolar mania
• Presence of neurological disorder that contraindicates TMS or neurophysiological recording: Seizure disorder Lifetime history of traumatic brain injury with loss of consciousness Neurodegenerative disorder (e.g., Alzheimer's Disease, Parkinson's Disease, Frontotemporal Dementia)
• Presence of other medical disorder that would make it too uncomfortable to sit or lie still for long recording periods
• Presence of standard contraindications for MRI or rTMS Metal in the body Currently pregnant Claustrophobia Significant sensitivity to noise Medical conditions or treatments that lower seizure threshold History of severe brain injury History of seizures/ epilepsy
• Currently taking anticholinergic mediation, neuroleptic medication, or sedative/ hypnotic medication Note: SSRI, cholinesterase inhibitors or NMDA receptor antagonists are allowed if patient has been on a stable regimen of four weeks prior to enrollment
• Currently taking chronic opiate medications or substances
• Currently taking naltrexone

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

Experimental: Neurostimulation Group; On one study day, participants will complete experimental tasks during functional magnetic resonance imaging. On two other study days, participants will complete tasks before and after receiving repetitive transcranial magnetic stimulation (rTMS). All participants will receive rTMS to ventromedial prefrontal cortex on one study day, and to pre-supplementary motor area on another study day. Two stimulation procedures will be used, one for ventromedial prefrontal cortex and one for pre-supplementary motor area. For both targets, 3 sessions of 600 pulses at 110% of resting motor threshold will be presented over 30 minutes. For ventromedial cortex, a session will involve intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds. For pre-supplementary motor area, a session will involve continuous theta burst presented in 3-pulse bursts with 15 pulses/ sec.

Device: Repetitive Transcranial Magnetic Stimulation (rTMS); A repetitive Transcranial Magnetic Stimulation (rTMS) MagVenture MagPro TMS System will be used to deliver intermittent theta burst to ventromedial prefrontal cortex, and continuous theta burst to pre-supplementary motor area.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fear-Potentiated Startle Reflex	Fear-potentiated startle is measured during an experimental task in which participants prepare to avoid, escape, or simply be exposed to aversive pictures. Fear-potentiated startle measures motivational activation during the preparation period.	Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 30 minutes between assessments)
Change in Speed to Initiate Avoidance Behavior	Reaction time to initiate flight is measured in an experimental task in which participants can win money but also must evade a slow, moderate, or fast virtual predator. Reaction time measures behavioral tendency to approach or avoid.	Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 30 minutes between assessments)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Escape/ Avoidance Electroencephalography	Electroencephalography (EEG) is measured during an experimental task in which participants prepare to avoid, escape, or simply be exposed to aversive pictures. An event-related potential, the stimulus-preceding negativity, will be derived from the EEG to index action preparation processing.	Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 30 minutes between assessments)
Change in Approach/ Avoidance Conflict Electroencephalography	Electroencephalography (EEG) is measured during an experimental task in which participants can win money but also must evade a slow, moderate, or fast virtual predator. A frequency signature, power in the theta frequency band, will be derived from the EEG to index cognitive control processes.	Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 30 minutes between assessments)
Change in Task-Related Heart Rate Changes	Heart rate is measured during experimental tasks in which: 1) participants prepare to avoid, escape, or simply be exposed to aversive pictures; 2) participants can win money but also must evade a slow, moderate, or fast virtual predator. Heart rate slowing measures task-related engagement of attention, while heart rate increase indicates defensive activation.	Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 30 minutes between assessments)
Change in Task-Related Skin Conductance Responding	Skin conductance is measured during experimental tasks in which: 1) participants prepare to avoid, escape, or simply be exposed to aversive pictures; 2) participants can win money but also must evade a slow, moderate, or fast virtual predator. Skin conductance increases indicate task-related sympathetic arousal.	Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 30 minutes between assessments)
Change in Task-Related Perceived Control	Perceived control over aversive stimuli is queried after an experimental task in which participants prepare to avoid, escape, or simply be exposed to aversive pictures. Perceived control for each condition is queried using self-report Likert-type scales for each condition.	Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 30 minutes between assessments)
Change in Difficulty of Avoiding Task-Based Aversive Exposure	Difficulty of avoiding exposure to aversive stimulation is queried after each trial during a task in which participants can win money but also must evade a slow, moderate, or fast virtual predator. Avoidance difficulty is queried using a Likert-type scale delivered after each trial. The scale ranges from 1 to 5, with higher scores indicating greater perceived difficulty of avoiding capture by the virtual predator.	Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 30 minutes between assessments)
Change in State Anxiety During Session	State-level anxiety is measured throughout the experimental session using the State-Trait Anxiety Inventory - State Form. The State-Trait Anxiety Inventory - State Form uses 20 items querying anxiety symptom experience in the present moment to measure how anxiety fluctuates across the experimental session. The scale ranges from 20 to 80, with higher scores indicating higher state anxiety.	Immediately Pre-Stimulation and Immediately Post-Stimulation (Approx. 30 minutes between assessments)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Task-Related Brain Activation	Blood flow in the brain will be measured during completion of two experimental tasks using functional magnetic resonance imaging (fMRI). Blood flow in the brain can be used to measure what brain areas are being activated during the performance of a task.	During Session (Approx. 45 minutes)

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: National Institute of Mental Health (NIMH)

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2021
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: March 24, 2021
• First Submitted That Met QC Criteria: March 26, 2021
• First Posted (Actual): April 1, 2021

Study Record Updates

• Last Update Posted (Estimated): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders
• Other Study ID Numbers: 00106843; 1K23MH123931-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Objective data will be archived in raw format on the NITRIC Data Repository. Sufficient description of tasks and event markers will be included to allow reprocessing and replication by trained researchers. Original, albeit cleaned and de-identified, self-report data will also be included. Cleaning will entail the most basic review of each variable to assure correct coding, and, in justified cases, invert variable scores to make variables easier to interpret. Inversions will always be noted.

DATA FORMAT: Objective data will be delivered to NITRIC in NIFTII format for fMRI data and tab-delimited text files for EEG and physiology data. Self-report data will be delivered in SPSS .sav format. No identifying information will be included.

VARIABLE CREATION: All variable computation, weighting, and imputation syntax will be in SPSS format and delivered in .txt file. A variable definition list / codebook will also be delivered.

• IPD Sharing Time Frame: Immediately following publication of primary project manuscript, or by 6 months after study completion, whichever is earlier.
• IPD Sharing Access Criteria: De-identified data will be made available through upload to the NITRIC Data Repository. As such, de-identified data will be publically available.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No