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Neuroimaging Biomarkers for Predicting rTMS Response in OCD

Primary Purpose

Obsessive-Compulsive Disorder

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Active bilateral DMPFC
Active right-sided OFC
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Obsessive-Compulsive Disorder focused on measuring transcranial magnetic stimulation, theta burst

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. meets Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for OCD with a moderate level of severity as defined by a Yale-Brown Obsessive Compulsive Scale (YBOCS) score of at least 18.
  2. stable on Serotonin Re-uptake Inhibitor (SRI) medication for at least 8 weeks prior to (with plans to continue throughout) the study Note: Medications that are known to increase cortical excitability (e.g., buprorion, maprotiline, tricyclic antidepressants, classical antipsychotics) or to have an inhibitory effect on brain excitability (e.g., anti-convulsants, benzodiazepines, and atypical antipsychotics), or any other medications with relative hazard for use in TMS will be allowed upon review of medications and/or motor threshold determination by TMS specialist.
  3. failed at least 1 prior trial of standard first-line OCD treatment per American Psychological Association (APA) Practice Guidelines (serotonin reuptake inhibitor [SRI] or cognitive behavioral therapy with exposure and response prevention)OR had refused these treatments for individual reasons.
  4. capacity to provide informed consent.
  5. ability to tolerate clinical study procedures.
  6. successfully complete the screening forms at the Stanford Center for Cognitive and Neurobiological Imaging (CNI) without any contraindications.

Exclusion Criteria:

  1. Current psychosis (re-assessed only if screening appointment was more than 30 days ago - Structured Clinical Interview for DSM-IV (SCID) - 5 Module B)
  2. Current bipolar disorder (assessed during baseline if screening appointment was more than 30 days ago - SCID-5 Module D)
  3. Severe depression [Note: 17-item Hamilton Depression Rating Scale (HDRS-17) must be less or equal to 20 to enter study, assessed during baseline if last assessment was more than 1 week ago]
  4. Current active suicidality (as determined by C-SSRS at baseline of 3 or above)
  5. Current moderate or severe Alcohol Usage Disorder or Substance Usage Disorder (except nicotine and caffeine) according to the DSM-5 criteria (assessed only if screening appointment was more than 12 months ago - SCID-5 Module E)
  6. Current eating disorder (assessed during baseline if screening appointment was more than 3 months ago - SCID-5 Module I)
  7. History of seizure, having an EEG, stroke, head injury (including neurosurgery), implanted devices, frequent or severe headaches, brain related conditions (e.g., intracranial mass lesions globe injuries, hydrocephalus), illness that caused brain injury or first degree relative with seizure disorder (assessed during screening via medical history assessment and TMS Safety Screen by study MD)
  8. Individuals with primary hoarding disorder without a DSM-5 OCD diagnosis (as determined by SCID-5 and YBOCS checklist assessed only if screening appointment was more than 30 days ago)
  9. Planning to commence Cognitive Behavioral Therapy (that includes exposure and response prevention) during the period of the study or have begun Cognitive Behavioral Therapy within 8 weeks prior to enrollment (assessed during baseline by study MD)
  10. Pregnant or nursing females (assessed via urine dipstick if screening appointment was more than 30 days ago)
  11. Positive urine screen for illicit drugs (assessed via urine dipstick if screening appointment was more than 30 days ago) [Exceptions: (1) any prescribed medication that participant is currently taking and (2) positive cocaine metabolite after consumption of coca tea]
  12. History of any implanted device or psychosurgery (assessed during baseline by study MD)
  13. History of receiving Electroconvulsive Therapy (ECT) (assessed during baseline by study MD)
  14. Age of OCD symptom onset >30

Sites / Locations

  • Department of Psychiatry and Behavioral Sciences, Stanford School of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

bilateral DMPFC

right OFC

Arm Description

This arm will receive intermittent theta-burst stimulation to bilateral DMPFC site.

This arm will receive continuous theta-burst stimulation to the right OFC site.

Outcomes

Primary Outcome Measures

Percentage change in Yale-Brown Obsessive-Compulsive Scale (YBOCS)
The YBOCS is a 10-item clinician-rated questionnaire that assesses the impact and severity of an individual's obsessive thoughts and compulsive behaviors. The minimum and maximum scores are 0 and 36, respectively, with higher score indicating greater severity.

Secondary Outcome Measures

Percent change in the Obsessive-Compulsive Inventory-Revised (OCI-R)
The Obsessive-Compulsive Inventory-Revised (OCI-R) has 18 items. Each item can be scored on a 5 point scale from 0 to 4. Total score can range from 0 to 72, with higher scores indicating more severe OCD.

Full Information

First Posted
February 21, 2020
Last Updated
April 16, 2023
Sponsor
Stanford University
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1. Study Identification

Unique Protocol Identification Number
NCT04286126
Brief Title
Neuroimaging Biomarkers for Predicting rTMS Response in OCD
Official Title
Individualized Neuroimaging Biomarkers for Predicting rTMS Response in OCD
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 15, 2021 (Actual)
Primary Completion Date
July 15, 2025 (Anticipated)
Study Completion Date
December 15, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study evaluates an accelerated schedule of theta-burst stimulation using a Transcranial Magnetic Stimulation (TMS) device for treatment-resistant Obsessive Compulsive Disorder (OCD). In a randomized fashion, half the participants will receive accelerated theta-burst stimulation at the dorsomedial prefrontal cortex (DMPFC), while half will receive accelerated theta-burst stimulation at the right orbitofrontal (rOFC) site.
Detailed Description
Medications (SSRIs and D2 antagonists) and cognitive-behavioral therapy are the mainstays of treating OCD; however, many patients show only a partial response, and more than 25% of patients show no improvement with these treatments. Repetitive transcranial magnetic stimulation (rTMS) is a promising alternative, using powerful, focused magnetic field pulses to stimulate target brain areas. So far, at least two stimulation targets have consistent evidence of efficacy in OCD: the dorsomedial prefrontal cortex (DMPFC) and the orbitofrontal cortex (OFC). Patients often show a strong response to one target but not the other. It is not well understood why some patients respond, while others do not. The investigators previously developed methods for discovering neurophysiological subtypes of depression based on resting state functional Magnetic Resonance Imaging (fMRI) measures of functional connectivity (RSFC) in relevant brain networks; diagnosing them in individual patients; and using them to predict individual differences in rTMS response. Subsequently, motivated by recent studies characterizing individual variability in the topology of these functional networks, the investigators have optimized methods for improving the accuracy of these predictions by accounting for individual variability, stabilizing the selection of treatment-predictive features, and increasing robustness in replication samples through regularization. Here, the investigators propose applying these methods to discover novel network-based subtypes of OCD and develop prognostic neuroimaging biomarkers for predicting differential treatment response to rTMS targeting the DMPFC or OFC, which could subsequently be tested in a randomized clinical trial.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obsessive-Compulsive Disorder
Keywords
transcranial magnetic stimulation, theta burst

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
bilateral DMPFC
Arm Type
Active Comparator
Arm Description
This arm will receive intermittent theta-burst stimulation to bilateral DMPFC site.
Arm Title
right OFC
Arm Type
Active Comparator
Arm Description
This arm will receive continuous theta-burst stimulation to the right OFC site.
Intervention Type
Device
Intervention Name(s)
Active bilateral DMPFC
Intervention Description
Participants in this arm will receive rTMS to bilateral DMPFC. The DMPFC will be targeted utilizing either Nexstim's eField neuronavigation system or Localite's neuronavigation system. Stimulation intensity will be standardized at 100% of resting motor threshold (RMT).
Intervention Type
Device
Intervention Name(s)
Active right-sided OFC
Intervention Description
Participants in this arm will receive rTMS to the right OFC. The right OFC will be targeted utilizing either Nexstim's eField neuronavigation system or Localite's neuronavigation system. Stimulation intensity will be standardized at 110% of resting motor threshold (RMT).
Primary Outcome Measure Information:
Title
Percentage change in Yale-Brown Obsessive-Compulsive Scale (YBOCS)
Description
The YBOCS is a 10-item clinician-rated questionnaire that assesses the impact and severity of an individual's obsessive thoughts and compulsive behaviors. The minimum and maximum scores are 0 and 36, respectively, with higher score indicating greater severity.
Time Frame
Baseline (Pretreatment) to immediate post-treatment follow up
Secondary Outcome Measure Information:
Title
Percent change in the Obsessive-Compulsive Inventory-Revised (OCI-R)
Description
The Obsessive-Compulsive Inventory-Revised (OCI-R) has 18 items. Each item can be scored on a 5 point scale from 0 to 4. Total score can range from 0 to 72, with higher scores indicating more severe OCD.
Time Frame
Baseline (Pretreatment) to immediate post-treatment follow up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: meets Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for OCD with a moderate level of severity as defined by a Yale-Brown Obsessive Compulsive Scale (YBOCS) score of at least 18. stable on Serotonin Re-uptake Inhibitor (SRI) medication for at least 8 weeks prior to (with plans to continue throughout) the study Note: Medications that are known to increase cortical excitability (e.g., buprorion, maprotiline, tricyclic antidepressants, classical antipsychotics) or to have an inhibitory effect on brain excitability (e.g., anti-convulsants, benzodiazepines, and atypical antipsychotics), or any other medications with relative hazard for use in TMS will be allowed upon review of medications and/or motor threshold determination by TMS specialist. failed at least 1 prior trial of standard first-line OCD treatment per American Psychological Association (APA) Practice Guidelines (serotonin reuptake inhibitor [SRI] or cognitive behavioral therapy with exposure and response prevention)OR had refused these treatments for individual reasons. capacity to provide informed consent. ability to tolerate clinical study procedures. successfully complete the screening forms at the Stanford Center for Cognitive and Neurobiological Imaging (CNI) without any contraindications. Exclusion Criteria: Current psychosis (re-assessed only if screening appointment was more than 30 days ago - Structured Clinical Interview for DSM-IV (SCID) - 5 Module B) Current bipolar disorder (assessed during baseline if screening appointment was more than 30 days ago - SCID-5 Module D) Severe depression [Note: 17-item Hamilton Depression Rating Scale (HDRS-17) must be less or equal to 20 to enter study, assessed during baseline if last assessment was more than 1 week ago] Current active suicidality (as determined by C-SSRS at baseline of 3 or above) Current moderate or severe Alcohol Usage Disorder or Substance Usage Disorder (except nicotine and caffeine) according to the DSM-5 criteria (assessed only if screening appointment was more than 12 months ago - SCID-5 Module E) Current eating disorder (assessed during baseline if screening appointment was more than 3 months ago - SCID-5 Module I) History of seizure, having an EEG, stroke, head injury (including neurosurgery), implanted devices, frequent or severe headaches, brain related conditions (e.g., intracranial mass lesions globe injuries, hydrocephalus), illness that caused brain injury or first degree relative with seizure disorder (assessed during screening via medical history assessment and TMS Safety Screen by study MD) Individuals with primary hoarding disorder without a DSM-5 OCD diagnosis (as determined by SCID-5 and YBOCS checklist assessed only if screening appointment was more than 30 days ago) Planning to commence Cognitive Behavioral Therapy (that includes exposure and response prevention) during the period of the study or have begun Cognitive Behavioral Therapy within 8 weeks prior to enrollment (assessed during baseline by study MD) Pregnant or nursing females (assessed via urine dipstick if screening appointment was more than 30 days ago) Positive urine screen for illicit drugs (assessed via urine dipstick if screening appointment was more than 30 days ago) [Exceptions: (1) any prescribed medication that participant is currently taking and (2) positive cocaine metabolite after consumption of coca tea] History of any implanted device or psychosurgery (assessed during baseline by study MD) History of receiving Electroconvulsive Therapy (ECT) (assessed during baseline by study MD) Age of OCD symptom onset >30
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nick Bassano, MSW
Phone
650-497-3933
Email
nbassano@stanford.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ian Kratter, MD, PhD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nick Bassano, MSW
Phone
650-497-3933
Email
nbassano@stanford.edu
First Name & Middle Initial & Last Name & Degree
Ian Kratter, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
No
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Neuroimaging Biomarkers for Predicting rTMS Response in OCD

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