Biomarkers of Depression and Treatment Response

NCT04581902 | Recruiting FDA Device

• 1 other identifier: 19-28340
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a stratified, parallel-group, single-center study utilizing multimodal imaging techniques to identify biomarkers for Major Depressive Disorder (MDD). The study goal is to identify biomarkers for MDD and treatment response that can be implemented in clinical diagnosis and care as valid and reliable measures, through monitoring neurophysiological and electrophysiological changes across the course of transcranial magnetic stimulation (TMS) treatment.

Conditions

Depressive Disorder, Major

Keywords

transcranial magnetic stimulation; depression; biomarker; TMS; neuroimaging; rTMS

Outcome Measures

Primary Outcomes (4)

• Change in MADRS score from baseline to end of treatment

  Effect size of active stimulation (mean difference in Montgomery Asberg Depression Rating Scale (MADRS) score) before and after morning and afternoon treatment course. Higher MADRS score indicates more severe depression; the overall score ranges from 0 to 60.

  Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)

• Change in resting state BOLD signal from baseline to end of treatment

  Change in resting state functional magnetic resonance imaging BOLD signal before and after the active treatment period.

  Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)

• Change in resting state EEG from baseline to end of treatment

  Change in resting state EEG (electroencephalogram) alpha band coherence before and after the active treatment period.

  Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)

• Change in white matter integrity from baseline to end of treatment

  Change in white matter integrity as measured by diffusion tensor imaging (DTI) before and after the active treatment period.

  Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)

Secondary Outcomes (4)

• Change in Beck's Depression Inventory (BDI) score from baseline to end of treatment

  Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)

• Change in Patient Health Questionnaire (PHQ9) score from baseline to end of treatment

  Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)

• Change in Generalized Anxiety Disorder (GAD-7) score from baseline to end of treatment

  Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)

• Change in Inventory of Depressive Symptomatology (IDS-30 self report) score from baseline to end of treatment.

  Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)

Study Arms (2)

Morning rTMS treatment

EXPERIMENTAL

Eligible participants will be assigned to the afternoon treatment group. Prior to the onset of rTMS treatment, EEG scans and magnetic resonance imaging (MRI) sessions including diffusion weighted imaging will be recorded as baseline measures. These measures will also be repeated at treatment midpoint and within one month of rTMS discontinuation in order to track structural and functional changes that occur over the course of treatment. Participants will complete an initial screening followed by 30-40 daily sessions of repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC), completed with their TMS provider.

Device: rTMS therapy

Afternoon rTMS treatment

EXPERIMENTAL

Eligible participants will be assigned to the afternoon treatment group. Prior to the onset of rTMS treatment, EEG scans and magnetic resonance imaging (MRI) sessions including diffusion weighted imaging will be recorded as baseline measures. These measures will also be repeated at treatment midpoint and within one month of rTMS discontinuation in order to track structural and functional changes that occur over the course of treatment. Participants will complete an initial screening followed by 30-40 daily sessions of repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC), completed with their TMS provider.

Device: rTMS therapy

Interventions

rTMS therapy DEVICE

rTMS treatment parameters will be determined by TMS care providers. Typical TMS settings for MDD involve rTMS applied at 10 Hz with an intensity of 120 % of resting motor threshold. Forty trains of 4 s duration with 11s of trains is typically applied (3000 pulses per day), resulting in approximately 90,000 pulses in a given treatment course.

Also known as: repetitive TMS, repetitive transcranial magnetic stimulation

Afternoon rTMS treatment; Morning rTMS treatment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-70
• Meet Diagnostic and Statistical Manual-V (DSM-V) diagnostic criteria for Major Depressive Disorder in a current major depressive episode, without psychotic features.
• Has Montgomery-Asberg Depressive Rating Scale (MADRS) of \> 19 at baseline, corresponding with moderate to severe depression.
• Demonstrate a moderate level of resistance to antidepressant treatment in the current episode, defined as a failure of 1-4 adequate medication trials.
• If participant is on a regimen of psychotropic medication, no changes in this regimen should be made during the period between the time at which pre-treatment and post-treatment scans are taken.
• Willing and able to undergo non-invasive brain stimulation
• Willing and able to attend research visits for approximately 8 weeks
• Willing and able to provide informed consent
• Ability to speak and read English

You may not qualify if:

• Diagnosed with acute or chronic psychotic symptoms of disorders (e.g. schizophrenia, schizophreniform, schizoaffective disorder) in the current depressive episode.
• Has neurological conditions including epilepsy, cerebrovascular disease, dementia, increased intracranial pressure, having a history of repetitive or severe head trauma, or with primary or secondary tumors in the central nervous system.
• Presence of an implanted magnetic-sensitive medical device in or near the head, including but not limited to pacemaker, vagus nerve stimulator, or metal aneurysm clips or coils, staples, or stents.
• Generalized anxiety disorder as the primary DSM-V disorder during the current MDD episode.
• Meets criteria for alcohol or substance abuse or dependence (other than caffeine) in previous 6 months, as determined by the SCID
• History of seizures
• Implantable hardware not compatible with MRI or with the study
• Inability to comply with study daily visits
• Women who are pregnant, plan to become pregnant, or breast feeding
• Inability to speak and/or read English
• Inability to give consent
• Any active suicidal intent or plan during the current depressive episode, as determined by a score of 3 on Question #9 of Beck's Depression Inventory (scores reviewed daily by study team members versed in scoring clinical scales), or as by a subjective determination by a study clinician during any study visit.

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Andrew Krystal, MD, MS

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katherine Scangos, MD, PhD

CONTACT

415-476-7439; brainstim@ucsf.edu

Rebecca Martinez, MS

CONTACT

rebecca.martinez@ucsf.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: A third party assessor will conduct a biweekly MADRS clinician rating to assess depression symptoms.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This will be a parallel-groups, stratified interventional study to investigate methods of optimizing clinical care in patients diagnosed with MDD.

Study Record Dates

• First Submitted: July 27, 2020
• First Posted: October 9, 2020
• Study Start: December 1, 2020
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: January 30, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)