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Individualized 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
Repetitive Transcranial Magnetic Stimulation
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 rTMS, fMRI, EEG

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Outpatient Aged 18-80 Either sex and all ethno-racial categories. Meets 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 20. Off antidepressants OR on a stable dose of SRI medication for at least 8 weeks prior to the study with plans to remain on this stable dose during the study. a. Medications that are known to increase cortical excitability (e.g., bupropion, maprotiline, tricyclic antidepressants, classical antipsychotics) or to have an inhibitory effect on brain excitability (e.g., anticonvulsants, 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 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 MRI safety screening forms without any contraindications. Exclusion Criteria: Diagnosed according to the MINI as suffering from a primary psychiatric diagnosis other than OCD. Evidence of psychotic symptoms on diagnostic interview. Diagnosed according to the MINI as suffering from severe Personality Disorder (excluding Obsessive-Compulsive Personality Disorder) or hospitalized due to exacerbation related to borderline personality disorder. Current bipolar disorder or history of any manic episodes. Current active suicidality Met criteria for moderate or severe Alcohol Use Disorder, Cannabis Use Disorder, or Substance Use Disorder (except nicotine and caffeine) within the past 3 months according to DSM-5 criteria. Current eating disorder 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. Significant neurological disorder or insult including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, history of cerebrovascular accident, transient ischemic attack within two years, cerebral aneurysm, dementia, Parkinson's disease, Huntington's chorea, multiple sclerosis, epilepsy. Individuals with primary hoarding disorder without a DSM-5 OCD diagnosis (as determined by MINI and YBOCS checklist). 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. Pregnant or nursing females (assessed via urine dipstick), or plans to conceive during the study. Positive urine screen for illicit drugs (assessed via urine dipstick) [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. History of any metal in the head including the eyes and ears (outside the mouth). Age of OCD symptom onset > 40. History of significant hearing loss. Head or neck tics which interfere with TMS and/or MRI. Subjects who suffered from an unstable physical, systemic and metabolic disorder such as unstabilized blood pressure or acute, unstable cardiac disease. Autism spectrum disorder aTBS treatment dose > 65% maximum stimulator output (MSO) Any other condition deemed by the PD to interfere with the study or increase risk to the participant

Sites / Locations

  • Stanford UniversityRecruiting
  • Weill Cornell MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Medial Prefrontal Cortex (MPFC)

Right Prefrontal Cortex (rPFC)

Arm Description

Intermittent theta-burst stimulation (iTBS) of MPFC at up to 100% resting motor threshold (RMT), with lower extremity RMT established for the MPFC target.

Continuous theta-burst stimulation (cTBS) of rPFC at up to 110% of RMT, with upper extremity RMT established for the rPFC target.

Outcomes

Primary Outcome Measures

resting-state functional connectivity (rsFC) of frontostriatal networks
functional magnetic resonance imaging (fMRI) measures of resting-state functional connectivity (rsFC) in the frontostriatal networks targeted by rTMS (MPFC or rPFC)

Secondary Outcome Measures

OCD symptoms
Change in OCD symptoms (YBOCS 2, Yale-Brown Obsessive Compulsive Scale 2, score range: 0-50, higher scores indicating higher symptom levels) following treatment with rTMS

Full Information

First Posted
April 6, 2023
Last Updated
May 10, 2023
Sponsor
Stanford University
Collaborators
Cornell University, Foundation for OCD Research
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1. Study Identification

Unique Protocol Identification Number
NCT05829681
Brief Title
Individualized Neuroimaging Biomarkers for Predicting rTMS Response in OCD
Official Title
Individualized Neuroimaging Biomarkers for Predicting Repetitive Transcranial Magnetic Stimulation (rTMS) Response in Obsessive Compulsive Disorder (OCD)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 14, 2022 (Actual)
Primary Completion Date
March 14, 2027 (Anticipated)
Study Completion Date
March 14, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University
Collaborators
Cornell University, Foundation for OCD Research

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
Yes

5. Study Description

Brief Summary
The goal of this clinical trial is to discover brain-based subtypes of Obsessive Compulsive Disorder (OCD) and examine treatment response to two different repetitive transcranial magnetic stimulation (rTMS) targets in the brain: the medial prefrontal cortex (MPFC) and the right prefrontal cortex (rPFC).
Detailed Description
New interventions are urgently needed to treat obsessive compulsive disorder (OCD), as more than 25% of patients show no improvement with the standard of care. Repetitive transcranial magnetic stimulation (rTMS) is a promising alternative treatment, as it uses focused magnetic field pulses to stimulate specific brain areas. So far, medial and right prefrontal cortex stimulation targets have consistent evidence of efficacy in OCD. 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. So far, there are no biomarkers for predicting treatment response, identifying the optimal neuroanatomical target, or choosing between treatments. The goal of this clinical trial is OCD subtype discovery and treatment optimization. Using MRI scans of OCD patients before and after rTMS treatment we aim to: Define novel network-based subtypes of OCD that can be diagnosed in individual patients and differentiated from healthy controls; Identify characteristic functional connectivity profiles predictive of response to MPFC-rTMS versus rPFC-rTMS; Identify characteristic changes in resting-state functional connectivity (RSFC) associated with symptom improvement for OCD patients undergoing MPFC- and rPFC-rTMS.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obsessive-Compulsive Disorder
Keywords
rTMS, fMRI, EEG

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Medial Prefrontal Cortex (MPFC)
Arm Type
Experimental
Arm Description
Intermittent theta-burst stimulation (iTBS) of MPFC at up to 100% resting motor threshold (RMT), with lower extremity RMT established for the MPFC target.
Arm Title
Right Prefrontal Cortex (rPFC)
Arm Type
Active Comparator
Arm Description
Continuous theta-burst stimulation (cTBS) of rPFC at up to 110% of RMT, with upper extremity RMT established for the rPFC target.
Intervention Type
Device
Intervention Name(s)
Repetitive Transcranial Magnetic Stimulation
Other Intervention Name(s)
rTMS, MagVenture MagPro rTMS Research System
Intervention Description
Participants will receive a 5-day course of 10x daily rTMS, with sessions delivered hourly. Each session will deliver up to 1800 pulses of theta-burst stimulation per target.
Primary Outcome Measure Information:
Title
resting-state functional connectivity (rsFC) of frontostriatal networks
Description
functional magnetic resonance imaging (fMRI) measures of resting-state functional connectivity (rsFC) in the frontostriatal networks targeted by rTMS (MPFC or rPFC)
Time Frame
pre-treatment up to 1-month post-treatment
Secondary Outcome Measure Information:
Title
OCD symptoms
Description
Change in OCD symptoms (YBOCS 2, Yale-Brown Obsessive Compulsive Scale 2, score range: 0-50, higher scores indicating higher symptom levels) following treatment with rTMS
Time Frame
pre-treatment to 1-week post-treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Outpatient Aged 18-80 Either sex and all ethno-racial categories. Meets 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 20. Off antidepressants OR on a stable dose of SRI medication for at least 8 weeks prior to the study with plans to remain on this stable dose during the study. a. Medications that are known to increase cortical excitability (e.g., bupropion, maprotiline, tricyclic antidepressants, classical antipsychotics) or to have an inhibitory effect on brain excitability (e.g., anticonvulsants, 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 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 MRI safety screening forms without any contraindications. Exclusion Criteria: Diagnosed according to the MINI as suffering from a primary psychiatric diagnosis other than OCD. Evidence of psychotic symptoms on diagnostic interview. Diagnosed according to the MINI as suffering from severe Personality Disorder (excluding Obsessive-Compulsive Personality Disorder) or hospitalized due to exacerbation related to borderline personality disorder. Current bipolar disorder or history of any manic episodes. Current active suicidality Met criteria for moderate or severe Alcohol Use Disorder, Cannabis Use Disorder, or Substance Use Disorder (except nicotine and caffeine) within the past 3 months according to DSM-5 criteria. Current eating disorder 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. Significant neurological disorder or insult including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, history of cerebrovascular accident, transient ischemic attack within two years, cerebral aneurysm, dementia, Parkinson's disease, Huntington's chorea, multiple sclerosis, epilepsy. Individuals with primary hoarding disorder without a DSM-5 OCD diagnosis (as determined by MINI and YBOCS checklist). 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. Pregnant or nursing females (assessed via urine dipstick), or plans to conceive during the study. Positive urine screen for illicit drugs (assessed via urine dipstick) [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. History of any metal in the head including the eyes and ears (outside the mouth). Age of OCD symptom onset > 40. History of significant hearing loss. Head or neck tics which interfere with TMS and/or MRI. Subjects who suffered from an unstable physical, systemic and metabolic disorder such as unstabilized blood pressure or acute, unstable cardiac disease. Autism spectrum disorder aTBS treatment dose > 65% maximum stimulator output (MSO) Any other condition deemed by the PD to interfere with the study or increase risk to the participant
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Flint Espil, PhD
Phone
650-498-9737
Email
espil@stanford.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Jennifer Lissemore, PhD
Email
jenliss@stanford.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Spiegel, MD
Organizational Affiliation
Stanford University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Nolan Williams, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94304
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Flint Espil, PhD
Phone
650-498-9737
Email
espil@stanford.edu
First Name & Middle Initial & Last Name & Degree
Nolan Williams, MD
Facility Name
Weill Cornell Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lindsay Victoria, PhD
Phone
646-962-3973
Email
liv3002@med.cornell.edu
First Name & Middle Initial & Last Name & Degree
Conor Liston, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The project will implement open data dissemination to ensure that the other FFOR teams and subsequently the wider research community will have ready access to the acquired data, including clinical and neuroimaging data from patients before and after treatment. To this end, all consent forms and datasharing agreements across the recruiting sites will incorporate content to enable this open data-sharing.
IPD Sharing Time Frame
Deidentified data will be available any time following publication of outcomes from this study, with no specified end date.
IPD Sharing Access Criteria
Deidentified data will be shared with any researcher requesting access.

Learn more about this trial

Individualized Neuroimaging Biomarkers for Predicting rTMS Response in OCD

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