Neural Circuit Biomarkers of Transcranial Magnetic Stimulation Study

Depression Clinical Trial

Official title:

Mechanistic Circuit Markers of Transcranial Magnetic Stimulation Outcomes in Pharmacoresistant Depression

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04663841
• Other study ID #: 52695
• Status: Recruiting
• Start date: November 2, 2020
• Est. completion date: December 31, 2026

Study information

• Verified date: March 2024
• Source: Stanford University
• Contact: Leanne Williams, PhD
• Phone: 650-723-3579
• Email: leawillliams[@]stanford.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study is currently recruiting Veterans only. The objective of this observational study is to test whether neuroimaging biomarkers of repetitive transcranial magnetic stimulation (TMS) can be prospectively replicated in a large ecologically valid sample. We focus on cognitive network connectivity as a predictive biomarker of the clinical effect of TMS, and as a response biomarker of change with TMS. We address this objective through a pragmatic approach in which we recruit patients undergoing routine clinical care and program evaluation in a Veterans Administration multi-site clinical TMS program.

Description:

Although repetitive transcranial magnetic stimulation (TMS) is becoming a gold standard treatment for pharmacoresistant depression, we lack neural target biomarkers for identifying who is most likely to respond to TMS and why. To address this gap in knowledge this observational study evaluates neural targets defined by activation and functional connectivity of the dorsolateral prefrontal cortex-anchored cognitive control circuit, regions of the default mode network and attention circuit, and interactions with the subgenual anterior cingulate.

The study evaluates whether these targets and interactions between them change in a dose-dependent manner, whether changes in these neural targets correspond to changes in cognitive behavioral performance, and whether baseline and early change in neural target and cognitive behavioral performance predict subsequent symptom severity, suicidality, and quality of life outcomes.

This study is designed as a pragmatic, mechanistic observational trial partnering with the National Clinical TMS Program of the Veteran's Health Administration.

All veterans will receive a clinical course of TMS as part of their routine care. Those who agree to enrollment in the observational study will be assessed at 'baseline' prior to commencement of their TMS treatment, 'first week' after initiation of TMS (targeting five sessions) and 'post-treatment' at the completion of TMS (targeting 30 sessions).

Veterans will be assessed using functional magnetic resonance imaging (fMRI), a cognitive behavioral performance battery, and established questionnaires.

To our knowledge, our study will be the first pragmatic, mechanistic observational trial to use fMRI imaging and cognitive-behavioral performance as biomarkers of TMS treatment response in pharmacoresistant MDD.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Ages 18 years and older

• Meets Diagnostic and Statistical Manual edition 5 (DSM-5) criteria for Major Depressive Disorder (MDD) (as documented by the treating physician)

• Meet study criteria for pharmacoresistance in accordance with the Clinical transcranial magnetic stimulation (TMS) Program (i.e. failed at least one antidepressant in the current episode)

• Ability to obtain a motor threshold (MT) prior to the start of treatment

• Stable medical conditions and ability to maintain stability on current medication regimen for the duration of treatment

• Ability to participate in a daily treatment regimen

• Able to read, verbalize understanding, and voluntarily sign the Informed Consent Form prior to participating in any study-specific procedures or assessments

Exclusion Criteria:

• History of seizure disorder

• Structural or neurologic abnormalities present or in close proximity to the treatment site

• History of brain surgery

• Pacemaker or medical infusion device (unless magnetic resonance imaging compatible)

• History of traumatic brain injury within 60 days of the start of treatment

• Severe or uncontrolled alcohol or substance use disorders

• Active withdrawal from alcohol or substances

• Implanted device in the head

• Metal in the head

• Severe impediment to vision, hearing and/or hand movement, likely to interfere with ability to complete the assessments, or unable and/or unlikely to follow the study protocols

• Lifetime history of bipolar I disorder

• Inability to speak, read or understand English

• Plans to move out of the area during the study period

• Clinician and/or Investigator discretion for clinical safety or protocol adherence

Related Conditions & MeSH terms

• Depression
• Depressive Disorder

Intervention

Other:
• transcranial magnetic stimulation
transcranial magnetic stimulation is delivered as part of routine care and is not managed by this observational study

Locations

Country	Name	City	State
United States	Stanford University Department of Psychiatry	Stanford	California

Sponsors (12)

Lead Sponsor	Collaborator
Stanford University	Brown University, Dartmouth College, Dartmouth-Hitchcock Medical Center, Florida State University, Medical University of South Carolina, Minneapolis Veterans Affairs Medical Center, Providence VA Medical Center, University of Minnesota, University of South Florida, VA Palo Alto Health Care System, White River Junction VA Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Go-NoGo elicited neural circuit function	Activation and connectivity assessed using functional magnetic resonance imaging during a GoNoGo task	Baseline
Primary	Go-NoGo elicited neural circuit function	Activation and connectivity assessed using functional magnetic resonance imaging during a GoNoGo task	Up to 2 weeks
Primary	Go-NoGo elicited neural circuit function	Activation and connectivity assessed using functional magnetic resonance imaging during a GoNoGo task	Up to 8 weeks
Primary	N-Back elicited neural circuit function	Activation and connectivity assessed using functional magnetic resonance imaging during an N-Back task	Baseline
Primary	N-Back elicited neural circuit function	Activation and connectivity assessed using functional magnetic resonance imaging during an N-Back task	Up to 2 weeks
Primary	N-Back elicited neural circuit function	Activation and connectivity assessed using functional magnetic resonance imaging during an N-Back task	Up to 8 weeks
Primary	Resting state neural circuit function	connectivity assessed using functional magnetic resonance imaging during a resting condition	Baseline
Primary	Resting state neural circuit function	connectivity assessed using functional magnetic resonance imaging during a resting condition	Up to 2 weeks
Primary	Resting state neural circuit function	connectivity assessed using functional magnetic resonance imaging during a resting condition	Up to 8 weeks
Secondary	Symbol Digit Coding Test	Cognitive-Behavioral Performance accuracy on the Symbol Digit Coding Test	Baseline
Secondary	Symbol Digit Coding Test	Cognitive-Behavioral Performance accuracy on the Symbol Digit Coding Test	Up to 2 weeks
Secondary	Symbol Digit Coding Test	Cognitive-Behavioral Performance accuracy on the Symbol Digit Coding Test	Up to 8 weeks
Secondary	Stroop Test	Cognitive-Behavioral Performance accuracy and reaction time on the Stroop Test	Baseline
Secondary	Stroop Test	Cognitive-Behavioral Performance accuracy and reaction time on the Stroop Test	Up to 2 weeks
Secondary	Stroop Test	Cognitive-Behavioral Performance accuracy and reaction time on the Stroop Test	Up to 8 weeks
Secondary	Shifting Attention Test	Cognitive-Behavioral Performance accuracy and reaction time on the Shifting Attention Test	Baseline
Secondary	Shifting Attention Test	Cognitive-Behavioral Performance accuracy and reaction time on the Shifting Attention Test	Up to 2 weeks
Secondary	Shifting Attention Test	Cognitive-Behavioral Performance accuracy and reaction time on the Shifting Attention Test	Up to 8 weeks
Secondary	Continuous Performance Test	Cognitive-Behavioral Performance accuracy and reaction time on the Continuous Performance Test platform	Baseline
Secondary	Continuous Performance Test	Cognitive-Behavioral Performance accuracy and reaction time on the Continuous Performance Test platform	Up to 2 weeks
Secondary	Continuous Performance Test	Cognitive-Behavioral Performance accuracy and reaction time on the Continuous Performance Test platform	Up to 8 weeks
Secondary	Depressive Symptoms	Clinical outcome assessed using the Quick Inventory of Depressive Symptoms (QIDS)- Self Report Form. The total score ranges from 0 to 27 with higher scores indicating greater severity.	Baseline
Secondary	Depressive Symptoms	Clinical outcome assessed using the Quick Inventory of Depressive Symptoms (QIDS)- Self Report Form. The total score ranges from 0 to 27 with higher scores indicating greater severity.	Up to 2 weeks
Secondary	Depressive Symptoms	Clinical outcome assessed using the Quick Inventory of Depressive Symptoms (QIDS)- Self Report Form. The total score ranges from 0 to 27 with higher scores indicating greater severity.	Up to 8 weeks
Secondary	Daily function related to quality of life	Clinical outcome assessed using the Veterans' RAND 36-item Health Survey (VR-36). All questions are scored on a scale from 0 to 100, with 100 representing the highest level of functioning possible.	Baseline
Secondary	Daily function related to quality of life	Clinical outcome assessed using the Veterans' RAND 36-item Health Survey (VR-36). All questions are scored on a scale from 0 to 100, with 100 representing the highest level of functioning possible.	Up to 2 weeks
Secondary	Daily function related to quality of life	Clinical outcome assessed using the Veterans' RAND 36-item Health Survey (VR-36). All questions are scored on a scale from 0 to 100, with 100 representing the highest level of functioning possible.	Up to 8 weeks
Secondary	Suicidal ideation	Columbia-Suicide Severity Rating Scale (C-SSRS). The total score ranges from 2 to 25, with a higher number indicating more intense ideation and greater risk.	Baseline
Secondary	Suicidal ideation	Columbia-Suicide Severity Rating Scale (C-SSRS). The total score ranges from 2 to 25, with a higher number indicating more intense ideation and greater risk.	Up to 2 weeks
Secondary	Suicidal ideation	Columbia-Suicide Severity Rating Scale (C-SSRS). The total score ranges from 2 to 25, with a higher number indicating more intense ideation and greater risk.	Up to 8 weeks