Neuroimaging Biomarkers for Predicting rTMS Response in OCD

April 16, 2023 updated by: Ian Kratter, Stanford University

Individualized Neuroimaging Biomarkers for Predicting rTMS Response in OCD

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

180

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Stanford, California, United States, 94305
        • Recruiting
        • Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine
        • Contact:
        • Principal Investigator:
          • Ian Kratter, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: bilateral DMPFC
This arm will receive intermittent theta-burst stimulation to bilateral DMPFC site.
Device: Active bilateral DMPFC
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).
Active Comparator: right OFC
This arm will receive continuous theta-burst stimulation to the right OFC site.
Device: Active right-sided OFC
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage change in Yale-Brown Obsessive-Compulsive Scale (YBOCS)
Time Frame: Baseline (Pretreatment) to immediate post-treatment follow up
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.
Baseline (Pretreatment) to immediate post-treatment follow up

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent change in the Obsessive-Compulsive Inventory-Revised (OCI-R)
Time Frame: Baseline (Pretreatment) to immediate post-treatment follow up
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.
Baseline (Pretreatment) to immediate post-treatment follow up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Investigators

  • Principal Investigator: Ian Kratter, MD, PhD, Stanford University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 15, 2021

Primary Completion (Anticipated)

July 15, 2025

Study Completion (Anticipated)

December 15, 2025

Study Registration Dates

First Submitted

February 21, 2020

First Submitted That Met QC Criteria

February 24, 2020

First Posted (Actual)

February 26, 2020

Study Record Updates

Last Update Posted (Actual)

April 18, 2023

Last Update Submitted That Met QC Criteria

April 16, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 53879

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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