Biomarkers of Depression and Treatment Response

Depressive Disorder, Major Clinical Trial

— SUNSET  

Official title:

Biomarkers of Depression and Treatment Response

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04581902
• Other study ID #: 19-28340
• Status: Recruiting
• Phase: N/A
• Start date: December 1, 2020
• Est. completion date: December 2025

Study information

• Verified date: November 2023
• Source: University of California, San Francisco
• Contact: Katherine Scangos, MD, PhD
• Phone: 415-476-7439
• Email: brainstim[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

First, the study will examine the replicability and prognostic utility of two previously identified potential biomarkers for MDD using resting state imaging. Second, investigators will conduct an exploratory, whole brain analysis combining EEG and imaging techniques to identify new potential biomarkers for MDD and treatment response as participants complete a course of TMS treatment. It is the hope to shed new light on the mechanisms underlying depression and relapse, which may allow for a more effective, personalized selection of treatment course.

Participants will complete initial screening and baseline evaluation, along with resting-state functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI) and electroencephalography (EEG) scans prior to the initial TMS treatment. Participants will complete 30-36 TMS sessions and a post-treatment evaluation, along with mid- and post-treatment fMRI, DTI and EEG scans.

It is anticipated that participants with MDD have a specific set of neural features that can classify with high precision patients with MDD from those who do not, and that align with clinical diagnoses. This set of neural features will change across the course of treatment. Further, investigators expect that improvement as rated by a common MDD measure is modulated by time of treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major

Intervention

Device:
• rTMS therapy
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.

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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	Change in Beck's Depression Inventory (BDI) score from baseline to end of treatment	The difference in Beck's Depression Inventory (BDI) score after TMS treatment course.Higher BDI score indicates more severe depression; the overall score ranges from 0 to 63.	Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)
Secondary	Change in Patient Health Questionnaire (PHQ9) score from baseline to end of treatment	The difference in Patient Health Questionnaire (PHQ9) score after TMS treatment course. Higher PHQ9 score indicates more severe depression; the overall score ranges from 0 to 27.	Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)
Secondary	Change in Generalized Anxiety Disorder (GAD-7) score from baseline to end of treatment	The difference in Generalized Anxiety Disorder (GAD-7) score after TMS treatment course. Higher GAD7 score indicates more severe depression; the overall score ranges from 0 to 21.	Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)
Secondary	Change in Inventory of Depressive Symptomatology (IDS-30 self report) score from baseline to end of treatment.	The difference in Inventory of Depressive Symptomatology Self-Report (IDS-SR) score after TMS treatment course. Higher IDS score indicates more severe depression; the overall score ranges from 0 to 84.	Up to one month prior to initial TMS session (baseline) to within one month following the completion of TMS treatment (~ 8 weeks)