Improving Brain Stimulation Through Imaging

NCT03851380 | Active Not Recruiting FDA Device

• 2 other identifiers: D3152-R48212
• Study Type: observational
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

Repetitive pulse transcranial magnetic stimulation (rTMS) is a noninvasive treatment that involves stimulating the brain; however, treatment benefit depends on placing a TMS coil in the correct place on the head to reach critical brain regions below. Clinicians typically use scalp-based targeting, a process in which rather than using MRI guidance to target brain regions for stimulation, they use landmarks on the scalp. Several researchers, including the investigators' lab, showed that the current scalp-based targeting techniques do not position stimulation above the correct brain region, and patients fail to respond. The investigators propose to improve clinical scalp-based targeting by comparing it to MRI guided targeting. The most common clinical population receiving rTMS therapy is depressed patients. The investigators' plan is to study the accuracy of certain scalp-based rules in patients with depression. Accurate brain stimulation targeting is critical for effective rTMS therapy. For participants who are not undergoing rTMS therapy who have COVID-19 distress, we are offering a combined home-based neuromodulation (transcranial electrical stimulation) and focused psychotherapy program dedicated to improving the same outcome measure, quality of life. Transcranial electrical stimulation (tES) stimulates the brain over a large region; however, we are able to model with brain imaging which brain regions receive the strongest stimulation. Our goal is still to examine stimulation precision, but we will test whether strength of tES in the same brain regions that rTMS is targeting will also lead to improved quality of life. We will also carefully assess whether it is possible to measure healthy functioning, an outcome in the rTMS study, because sheltering in place may reduce activities and thus distort our measure. We will also test whether our psychotherapy intervention will mitigate this effect and, if so, we may make it available to all those depressed Veterans in whom we're studying the effect of neuromodulation on functioning.

Conditions

Depression; Depressive Disorder, Treatment-Resistant; COVID Stress

Keywords

Transcranial Magnetic Stimulation; Magnetic Resonance Imaging; Functional Magnetic Resonance Imaging; fMRI; TMS; Neuronavigation; MRI; Transcranial Electrical Stimulation; COVID Stress

Outcome Measures

Primary Outcomes (2)

• World Health Organization Disability Assessment Schedule 2.0

  Assessment of global functioning. Range from 0 to 100 (0 = no disability, 100 = full disability).

  Baseline

• Veterans RAND 36-Item

  Assessment of self-reported health-related quality of life. Physical and Mental Component Scores (PCS and MCS) are normed (x = 50, sd = 10) and range from 0 to 100 (0 = worst health, 100 = best health).

  Baseline

Secondary Outcomes (1)

• Hamilton Depression Rating Scale-17 Items (HAMD-17)

  Baseline

Study Arms (2)

Treatment Resistant Major Depression

Patients with treatment resistant major depression

Behavioral: Psychological / Functional Assessment; Other: Structural and Functional MRI; Device: Transcranial Magnetic Brain Stimulation and MR Image Guidance

COVID Stress

Veterans with COVID-19-related distress

Behavioral: Psychological / Functional Assessment; Other: Structural and Functional MRI; Device: Transcranial Electrical Stimulation (tES)

Interventions

Psychological / Functional Assessment BEHAVIORAL

Psychological and functional assessment battery to characterize participants.

COVID Stress; Treatment Resistant Major Depression

Structural and Functional MRI OTHER

Structural and functional magnetic resonance imaging session.

COVID Stress; Treatment Resistant Major Depression

Transcranial Magnetic Brain Stimulation and MR Image Guidance DEVICE

MRI guided transcranial magnetic stimulation and measurement of targeting accuracy.

Treatment Resistant Major Depression

Transcranial Electrical Stimulation (tES) DEVICE

Home-based Transcranial Direct Current Stimulation

COVID Stress

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Veteran patients with depression or COVID-19-related distress

You may qualify if:

• Cohort 1:
• Capacity and willingness to participant in TMS, and fMRI as well as satisfying criteria for diagnosis.
• Between 18 and 89 years of age.
• Ability to obtain a Motor Threshold (MT) with single pulse TMS
• Ability to safely and comfortably undergo an MRI and TMS
• Able to read, verbalize, understand and voluntarily sign the Informed Consent Form prior to participating in any study-specific procedures or assessments
• Depression (PHQ-9 \>= 10 and functional impairment present indicated with "difficulty" question OR sufficiently depressed to be enrolled in rTMS therapy)
• Confirmed diagnosis of Major Depressive Disorder (MDD)
• Can maintain all existing treatments (e.g. psychopharmacology, psychotherapy, etc.,) throughout course of the three sessions (psychological / functional assessments, MRI, and TMS), with modifications only as needed for clinical management
• Is a Veteran
• Cohort 2:
• Between 18 and 89 years of age
• Ability to safely and comfortably undergo an MRI and tES
• Ability to read, verbalize, understand, and voluntarily sign the Informed Consent Form prior to participating in any study-specific procedures or assessments
• Depression (PHQ-9 \>= 10) and endorse that the COVID-19 pandemic has worsened their depression OR have a score on the COVID Stress Scale (CSS) on any item of 3 or greater indicating stressor is "very" or "often" a problem will allow the Veteran to enter the study

You may not qualify if:

• Participants who can not safely and comfortably undergo MRI OR TMS (or TES for Cohort 2)
• If their language is not primarily English they may be excluded depending on how dependent the imaging and cognitive tasks are on language
• Additionally, participants may be excluded if they do not fully understand the consenting process and cannot communicate sufficiently in English to participate in the therapy (d/t language barrier, etc.)
• An example of safety screen details for an MRI is detailed in the Stanford University MRI screening form
• For TMS the investigators will follow safety guidelines set by Rossi et. al.,2009
• Specifically, the investigators will not include subjects whose Motor Threshold (MT) is greater than 84% of maximum device output because mathematically they would not be able to be safely stimulated using the standard 120% of MT (i.e. the device cannot stimulate more than 100% of its potential output)
• Pregnant or planning to become pregnant within the next 3 months
• Lifetime history of moderate or severe traumatic brain injury, current unstable medical conditions, current (or past if appropriate) significant neurological disorder, or lifetime history of:
• seizure disorder
• primary or secondary CNS tumors
• stroke
• cerebral aneurysm
• Significant cognitive impairment (Montreal Cognitive Assessment \[MoCA\] \< 16)
• Comorbidities (e.g. PTSD) determined not to be the primary diagnosis
• Have a lifetime diagnosis of schizophrenia, schizoaffective disorder, schizophreniform, delusional disorder, or current psychotic symptoms

Sponsors & Collaborators

• VA Office of Research and Development: lead
• Providence VA Medical Center: collaborator
• Atlanta VA Medical Center: collaborator

Study Sites (1)

VA Palo Alto Health Care System, Palo Alto, CA

Palo Alto, California, 94304-1207, United States

Location

MeSH Terms

Conditions

Depression; Depressive Disorder, Treatment-Resistant

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Officials

• Allyson C Rosen, PhD

  VA Palo Alto Health Care System, Palo Alto, CA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2019
• First Posted: February 22, 2019
• Study Start: September 30, 2019
• Primary Completion: July 31, 2024
• Study Completion: May 1, 2026
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)