Improving Brain Stimulation Through Imaging

NCT03851380 | Completed FDA Device

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

Brief Summary

There are two protocols, one involving rTMS therapy in people with treatment resistant depression and one involving tDCS in people with stress from the COVID 19 pandemic. Clinic-Based rTMS Therapy: 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. Home-Based Neuromodulation: 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

PTSD - Post Traumatic Stress Disorder; 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; transcranial direct current stimulation; tDCS; tES

Outcome Measures

Primary Outcomes (2)

• Acceptable distance between TMS treatment location and brain target: Anticorrelation with Subgenual Cingulate

  Targeting accuracy was defined as being within 1.36 cm which is within the resolution of the TMS coil and which should be achievable based on work by Mir-Moghtadaei et al 2015 comparing to a fixed coordinate. The anticorrelation with the subgenual cingulate is a resting-state functional connectivity-based target that has evidence of being effective in reducing depression (Cash et al, 2020)

  [Within a week of clinical measures]

• Acceptable distance between TMS treatment location and brain target: fMRI Emotional Working Memory

  Targeting accuracy was defined as being within 1.36 cm which is within the resolution of the TMS coil and which should be achievable based on work by Mir-Moghtadaei et al 2015 comparing to a fixed coordinate. The peak fMRI coordinate will be identified within an a priori left dorsolateral prefrontal brain region. The fMRI Emotion Working Memory task involves holding in mind emotional and nonemotional images has been demonstrated to have strong cross-site reliability (Brown et al, 2011).

  [Within a week of clinical measures]

Secondary Outcomes (3)

• Correlation between change in World Health Organization Disability Assessment Schedule 2.0 (WHODAS) and distance from optimal TMS brain targets

  Within one week before beginning clinical rTMS therapy and within one week after rTMS therapy termination.

• Correlation between change in Veterans RAND 36-Item (VR-36) and distance from optimal TMS brain targets

  Within one week before beginning clinical rTMS therapy and within one week after rTMS therapy termination.

• Correlation between change in the Hamilton Depression Rating Scale-17 Items (HAMD-17) and distance from optimal TMS brain targets

  Within one week before beginning clinical rTMS therapy and within one week after rTMS therapy termination.

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

Related Publications (3)

• Mir-Moghtadaei A, Caballero R, Fried P, Fox MD, Lee K, Giacobbe P, Daskalakis ZJ, Blumberger DM, Downar J. Concordance Between BeamF3 and MRI-neuronavigated Target Sites for Repetitive Transcranial Magnetic Stimulation of the Left Dorsolateral Prefrontal Cortex. Brain Stimul. 2015 Sep-Oct;8(5):965-73. doi: 10.1016/j.brs.2015.05.008. Epub 2015 May 29.

  PMID: 26115776 BACKGROUND

• Brown GG, Mathalon DH, Stern H, Ford J, Mueller B, Greve DN, McCarthy G, Voyvodic J, Glover G, Diaz M, Yetter E, Ozyurt IB, Jorgensen KW, Wible CG, Turner JA, Thompson WK, Potkin SG; Function Biomedical Informatics Research Network. Multisite reliability of cognitive BOLD data. Neuroimage. 2011 Feb 1;54(3):2163-75. doi: 10.1016/j.neuroimage.2010.09.076. Epub 2010 Oct 13.

  PMID: 20932915 BACKGROUND

• Cash RFH, Weigand A, Zalesky A, Siddiqi SH, Downar J, Fitzgerald PB, Fox MD. Using Brain Imaging to Improve Spatial Targeting of Transcranial Magnetic Stimulation for Depression. Biol Psychiatry. 2021 Nov 15;90(10):689-700. doi: 10.1016/j.biopsych.2020.05.033. Epub 2020 Jun 7.

  PMID: 32800379 BACKGROUND

MeSH Terms

Conditions

Depression; Depressive Disorder, Treatment-Resistant; Combat Disorders

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders; Mental Disorders; Stress Disorders, Traumatic; Trauma and Stressor Related 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: COHORT
• Time Perspective: PROSPECTIVE
• 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: July 31, 2024
• Last Updated: August 3, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)