Theta Burst Stimulation for Compulsive Behavior Non-invasive Brain Stimulation Study

Testing the Causal Role of Orbitofrontal Cortex in Human Compulsive Behavior: a Non-invasive Brain Stimulation Study

This project seeks to identify causal neural mechanisms underlying unwanted, repetitive behaviors (compulsions). Using non-invasive brain stimulation coupled with practice in a computer task, we will modulate activity in a target brain region in two directions (up or down) and measure effects on compulsive behaviors and related measures. This work could ultimately lead to the ability to treat compulsions more effectively by targeting the regions of the brain that can help or hinder attempts to overcome compulsions.

Study Overview

• Status: Completed
• Conditions: Obsessive-Compulsive Disorder; Compulsive Behavior
• Intervention / Treatment: Behavioral: Habit Override Practice; Other: Transcranial Magnetic Stimulation

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Western Psychiatric Institute and Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Participants will:

1. Be between the ages of 18 and 55 years
2. Endorse problematic compulsive behaviors, per self-report and clinician-administered measures.
3. Agree to video taping of structured clinical interview
4. Report that they will reside in the Pittsburgh area for at least 5 weeks

Exclusion Criteria:

1. Failure to meet standard MRI inclusion criteria: those who endorse claustrophobia, those who have cardiac pacemakers, neural pacemakers, surgical clips in the brain or blood vessels, surgically implanted metal plates, screws or pins, cochlear implants, implanted uterine devices, metal braces, or other metal objects in their body, especially in the eye. Dental fillings do not present a problem. Plastic or removable dental appliances do not require exclusion. History of significant injury or surgery to the brain or spinal cord that would impair interpretation of results. Pregnancy, determined by pregnancy tests on females.

2. Medical contraindications for Transcranial Magnetic Stimulation (TMS):

   1. Presence of a neurologic disorder or medication therapy known to alter seizure threshold (e.g., stroke, aneurysm, brain surgery, structural brain lesion, brain injury, frequent/severe headaches)
   2. Recurrent seizures or epilepsy in participant or family history of hereditary epilepsy
   3. Pregnancy
   4. Metallic implants in body or other devices that may be affected by magnetic field
   5. Significant heart disease or cerebrovascular disease
   6. Medications with seizure threshold lowering potential, e.g., clomipramine, Monoamine Oxidase inhibitors (MAOi's), imipramine, clozapine
3. Acute suicidality or other psychiatric crises requiring treatment escalation
4. Changes made to treatment regimen within 4 weeks of baseline assessment
5. Reading level <6th grade
6. Presence of bipolar, psychotic, autism spectrum, or substance use disorder (i.e. current use of mood altering drugs such as cocaine, cannabis or marijuana, opiates, amphetamines, and barbiturates)
7. Presence of movement disorder or tics affecting manual responses
8. Inability to read text from 2 feet away (corrective lenses allowed)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: cTBS; Transcranial Magnetic Stimulation delivered in a continuous Theta Burst Stimulation (cTBS) pattern.	Behavioral: Habit Override Practice; Computerized "brain training" to provide practice in overriding avoidance habits.; Other: Transcranial Magnetic Stimulation; Non-invasive method for temporary, focal stimulation of brain areas.
ACTIVE_COMPARATOR: iTBS; Transcranial Magnetic Stimulation delivered in an intermittent Theta Burst Stimulation (iTBS) pattern.	Behavioral: Habit Override Practice; Computerized "brain training" to provide practice in overriding avoidance habits.; Other: Transcranial Magnetic Stimulation; Non-invasive method for temporary, focal stimulation of brain areas.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
functional Magnetic Resonance Imaging (fMRI)	Brain activation in target region	10-60min

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effort to resist compulsive behaviors in response to laboratory triggers	Custom-made laboratory assessment of ability to override compulsive behaviors in response to idiographic triggers: self-reported effort needed to resist	90min-1 week
Duration of compulsive behaviors in response to laboratory triggers	Custom-made laboratory assessment of ability to override compulsive behaviors in response to idiographic triggers: duration of compulsive behavior performance	90min-1 week
Intensity of urges to perform compulsive behaviors in response to laboratory triggers	Custom-made laboratory assessment of ability to override compulsive behaviors in response to idiographic triggers: self-reported urge intensity	90min-1 week
Two-step task	Neuropsychological test of flexible goal-directed cognition	90min-1 week
Yale-Brown Obsessive Compulsive Scale (Y-BOCS)	Clinician-administered measurement of obsessions and compulsions	1 week
WHO Disability Assessment Scale 2.0	Self-report measure of general functioning and disability	1 week
Obsessive Compulsive Inventory-Revised (OCI-R)	Self-report measure of obsessions and compulsions	1 week
Habit override task	Percentage of correct responses to each stimulus (0-100%; higher score=better performance)	1 week

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: National Institute of Mental Health (NIMH)

Publications and helpful links

General Publications

• Brown VM, Gillan CM, Renard M, Kaskie R, Degutis M, Wears A, Siegle GJ, Ferrarelli F, Ahmari SE, Price RB. A double-blind study assessing the impact of orbitofrontal theta burst stimulation on goal-directed behavior. J Psychopathol Clin Sci. 2022 Apr;131(3):287-300. doi: 10.1037/abn0000733. Epub 2022 Feb 7.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 15, 2017
• Primary Completion (ACTUAL): March 30, 2020
• Study Completion (ACTUAL): March 30, 2020

Study Registration Dates

• First Submitted: August 18, 2017
• First Submitted That Met QC Criteria: August 25, 2017
• First Posted (ACTUAL): August 29, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 16, 2022
• Last Update Submitted That Met QC Criteria: August 14, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders; Impulsive Behavior; Obsessive-Compulsive Disorder; Compulsive Behavior
• Other Study ID Numbers: STUDY19090219 (Part 1); R21MH112770 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will comply with all National Institute of Mental Health (NIMH) guidelines regarding data sharing and make use of NIMH databases.

Drug and device information, study documents

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