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Biomarkers of Depression and Treatment Response (SUNSET)

Primary Purpose

Depressive Disorder, Major

Status

Recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

rTMS therapy

About this trial

This is an interventional treatment trial for Depressive Disorder, Major focused on measuring transcranial magnetic stimulation, depression, biomarker, TMS, neuroimaging, rTMS

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of California, San FranciscoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Morning rTMS treatment

Afternoon rTMS treatment

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

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.

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.

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.

Secondary Outcome Measures

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.

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.

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.

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.

Full Information

NCT ID

NCT04581902

First Posted

July 27, 2020

Last Updated

April 26, 2023

Sponsor

University of California, San Francisco

1. Study Identification

Unique Protocol Identification Number

NCT04581902

Brief Title

Biomarkers of Depression and Treatment Response

Acronym

SUNSET

Official Title

Biomarkers of Depression and Treatment Response

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Recruiting

Study Start Date

December 1, 2020 (Actual)

Primary Completion Date

September 2023 (Anticipated)

Study Completion Date

December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of California, San Francisco

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Depressive Disorder, Major

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

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

Masking

Outcomes Assessor

Masking Description

A third party assessor will conduct a biweekly MADRS clinician rating to assess depression symptoms.

Allocation

Non-Randomized

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Morning rTMS treatment

Arm Type

Experimental

Arm Description

Arm Title

Afternoon rTMS treatment

Arm Type

Experimental

Arm Description

Intervention Type

Device

Intervention Name(s)

rTMS therapy

Other Intervention Name(s)

repetitive TMS, repetitive transcranial magnetic stimulation

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change in MADRS score from baseline to end of treatment

Description

Time Frame

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

Title

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

Description

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

Time Frame

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

Title

Change in resting state EEG from baseline to end of treatment

Description

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

Time Frame

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

Title

Change in white matter integrity from baseline to end of treatment

Description

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

Time Frame

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

Secondary Outcome Measure Information:

Title

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

Description

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.

Time Frame

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

Title

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

Description

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.

Time Frame

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

Title

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

Description

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.

Time Frame

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

Title

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

Description

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Katherine Scangos, MD, PhD

Phone

415-476-7439

brainstim@ucsf.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Rebecca Martinez, MS

rebecca.martinez@ucsf.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Andrew Krystal, MD, MS

Organizational Affiliation

University of California, San Francisco

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of California, San Francisco

City

San Francisco

State/Province

California

ZIP/Postal Code

94143

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Katherine Scangos, MD, PhD

Phone

415-476-7439

trdepression@ucsf.edu

First Name & Middle Initial & Last Name & Degree

Rebecca Martinez, MS

Phone

415- 514-6489

rebecca.martinez@ucsf.edu

First Name & Middle Initial & Last Name & Degree

Katherine Scangos, MD, PhD

First Name & Middle Initial & Last Name & Degree

Andrew Krystal, MD, MS

12. IPD Sharing Statement

Plan to Share IPD

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