Neuroimaging Biomarkers for Predicting rTMS Response in OCD

NCT ID: NCT04286126

Last Updated: 2023-04-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

180 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-15

Study Completion Date

2025-12-15

Brief Summary

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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

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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.

Conditions

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Obsessive-Compulsive Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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bilateral DMPFC

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

Group Type ACTIVE_COMPARATOR

Active bilateral DMPFC

Intervention Type DEVICE

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).

right OFC

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

Group Type ACTIVE_COMPARATOR

Active right-sided OFC

Intervention Type DEVICE

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).

Interventions

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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).

Intervention Type 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).

Intervention Type DEVICE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Stanford University

OTHER

Sponsor Role lead

Responsible Party

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Ian Kratter

Clinical Assistant Professor, Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ian Kratter, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

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Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine

Stanford, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Nick Bassano, MSW

Role: CONTACT

650-497-3933

Facility Contacts

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Nick Bassano, MSW

Role: primary

650-497-3933

References

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George MS, Lisanby SH, Avery D, McDonald WM, Durkalski V, Pavlicova M, Anderson B, Nahas Z, Bulow P, Zarkowski P, Holtzheimer PE 3rd, Schwartz T, Sackeim HA. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Arch Gen Psychiatry. 2010 May;67(5):507-16. doi: 10.1001/archgenpsychiatry.2010.46.

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George MS, Wassermann EM, Williams WA, Callahan A, Ketter TA, Basser P, Hallett M, Post RM. Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport. 1995 Oct 2;6(14):1853-6. doi: 10.1097/00001756-199510020-00008.

Reference Type BACKGROUND
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Pascual-Leone A, Rubio B, Pallardo F, Catala MD. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet. 1996 Jul 27;348(9022):233-7. doi: 10.1016/s0140-6736(96)01219-6.

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Chung SW, Hill AT, Rogasch NC, Hoy KE, Fitzgerald PB. Use of theta-burst stimulation in changing excitability of motor cortex: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2016 Apr;63:43-64. doi: 10.1016/j.neubiorev.2016.01.008. Epub 2016 Feb 3.

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Jelic MB, Milanovic SD, Filipovic SR. Differential effects of facilitatory and inhibitory theta burst stimulation of the primary motor cortex on motor learning. Clin Neurophysiol. 2015 May;126(5):1016-23. doi: 10.1016/j.clinph.2014.09.003. Epub 2014 Sep 16.

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Chung SW, Hoy KE, Fitzgerald PB. Theta-burst stimulation: a new form of TMS treatment for depression? Depress Anxiety. 2015 Mar;32(3):182-92. doi: 10.1002/da.22335. Epub 2014 Nov 28.

Reference Type BACKGROUND
PMID: 25450537 (View on PubMed)

Plewnia C, Pasqualetti P, Grosse S, Schlipf S, Wasserka B, Zwissler B, Fallgatter A. Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. J Affect Disord. 2014 Mar;156:219-23. doi: 10.1016/j.jad.2013.12.025. Epub 2013 Dec 28.

Reference Type BACKGROUND
PMID: 24411682 (View on PubMed)

Prasser J, Schecklmann M, Poeppl TB, Frank E, Kreuzer PM, Hajak G, Rupprecht R, Landgrebe M, Langguth B. Bilateral prefrontal rTMS and theta burst TMS as an add-on treatment for depression: a randomized placebo controlled trial. World J Biol Psychiatry. 2015 Jan;16(1):57-65. doi: 10.3109/15622975.2014.964768. Epub 2014 Nov 28.

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Daskalakis ZJ. Theta-burst transcranial magnetic stimulation in depression: when less may be more. Brain. 2014 Jul;137(Pt 7):1860-2. doi: 10.1093/brain/awu123. Epub 2014 May 15. No abstract available.

Reference Type BACKGROUND
PMID: 24833712 (View on PubMed)

Thut G, Pascual-Leone A. A review of combined TMS-EEG studies to characterize lasting effects of repetitive TMS and assess their usefulness in cognitive and clinical neuroscience. Brain Topogr. 2010 Jan;22(4):219-32. doi: 10.1007/s10548-009-0115-4. Epub 2009 Oct 28.

Reference Type BACKGROUND
PMID: 19862614 (View on PubMed)

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Reference Type BACKGROUND
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Reference Type BACKGROUND
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Greicius MD, Krasnow B, Reiss AL, Menon V. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):253-8. doi: 10.1073/pnas.0135058100. Epub 2002 Dec 27.

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Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9673-8. doi: 10.1073/pnas.0504136102. Epub 2005 Jun 23.

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Reference Type BACKGROUND
PMID: 18403396 (View on PubMed)

Other Identifiers

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53879

Identifier Type: -

Identifier Source: org_study_id

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