DepressionIBSINCT03851380
Improving Brain Stimulation Through Imaging
An observational study of Depression and Depressive Disorder, Treatment-Resistant, run by VA Office of Research and Development at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 89 years
- Conditions the study is for
- Depression, Depressive Disorder, Treatment-Resistant, COVID Stress
- What is being tested?
- Psychological / Functional Assessment, Structural and Functional MRI and Transcranial Magnetic Brain Stimulation and MR Image Guidance
- Type of treatment
- Medical device, Lifestyle or therapy programme
- How many people
- 54 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Sep 2019to 31 Jul 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Veteran patients with depression or COVID-19-related distress
Who may be able to join
- 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
Show all 15Show fewer
- 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
Who cannot join
- 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
- MRI exclusions include having any non-removable device or implant that makes scanning unsafe, claustrophobia, and size (e.g. weight, girth) beyond the constraints of the MRI and scanner bed
- For TMS the investigators will follow safety guidelines set by Rossi et. al.,2009
Show all 32Show fewer
- 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)
- The investigators will report these high MT data in our secondary analyses. Additional TMS exclusions include any history or condition that puts patients at risk for a seizure
- 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
- Have a diagnosis of obsessive-compulsive disorder assessed by a study investigator to be causing greater impairment than MDD
- Have active suicidal intent or plan in which case Dr. Rosen will determine whether the patient needs to be referred for hospitalization
- Presence of any other condition or circumstance that, in opinion of the investigator team, has the potential to prevent study completion and/or to have a confounding effect on outcome assessments
- Participants who cannot safely and comfortably undergo MRI or TES
- Pregnant or lactating female or planning to become pregnant within the next 3 months
- Lifetime history of moderate or severe traumatic brain injury or tumor
- Significant cognitive impairment (Montreal Cognitive Assessment [MoCA] < 16 OR equivalent score on [MoCA-BLIND] and judgement of a clinician that the test is validly reflecting a significant disabling cognitive impairment
- Have a lifetime diagnosis of:
- schizophrenia
- schizoaffective disorder
- schizophreniform
- delusional disorder
- or current psychotic symptoms
- Have a diagnosis of obsessive-compulsive disorder or unstable substance use disorder
- Presence of actively infections/contagious disease such as the flu or SARS-CoV-2
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Palo Alto Health Care System, Palo Alto, CA
Palo Alto, California, 94304-1207
About this study
Official title: Targeting Functional Improvement in rTMS Therapy
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.
Read the detailed description
Potential participants are first identified and contact is made. Potential participants are then screened for inclusionary and exclusionary information (see tab 9. Eligibility) that relate to whether they can safely and comfortably perform the procedures and whether they are considered healthy or have the disorder for which brain stimulation therapy will be delivered. They will undergo informed consent that will disclose all the different risks and benefits for the procedures they will undergo. The list of procedures in which participants consent to participate is below. Participants may do either or both of the activities detailed below.
PROCEDURES:
For participants in the MRI and TMS targeting activity:
- Psychological / functional assessments: Interview, computerized, and paper and pencil measures of psychological functioning. These measures are used to characterize patients' diagnosis and psychological status. For example, depressed patients will answer questions about depressive symptoms and potentially comorbid symptoms such as post-traumatic stress disorder. This testing typically lasts 2 hours.
- MRI and functional MRI Patients will undergo an MRI that indicates where they receive stimulation by a marker placed on a cap that displays brightly on an MRI. MRI will occur at Lucas center or the Palo Alto VA and involves brain imaging that will be related to brain stimulation techniques either through facilitating image guidance or providing information that will be correlated to data collected during stimulation. Typically, a session lasts about 2.5 hours since there is setup time involved.
- Brain Stimulation:
TMS-transcranial magnetic stimulation which will be collected at the Palo Alto VA. Part of this procedure may include electromyography (EMG) which involves placing electrodes on the skin, typically the hand, and measuring indicators of muscle contraction. Sometimes this information is used to decide stimulation intensity during TMS and sometimes the TMS induced response will be a source of data in itself. Typically, this is only a measure conducted in parallel with other procedures and thus will not be given its own consent. MRI Guided TMS. An MRI will be used to target a selective brain region. To accomplish this, the MRI will be displayed on a computer screen and an infrared camera enables identification of the correspondence between the image and the participant's head. To study errors in scalp-based targeting, the investigators will perform scalp targeting while under MRI guidance but without the typical visual feedback provided by the MRI. Then this will be compared to scalp targeting with MRI guidance. The difference will identify typical errors in scalp targeting. Typically, a session will last approximately 1.5 hours.
For participants in the home-based neuromodulation and focused psychotherapy program:
- Psychological / functional assessments: Interview, computerized, and paper and pencil measures of psychological functioning. These measures are used to characterize patients' diagnosis and psychological status. For example, depressed patients will answer questions about depressive symptoms and potentially comorbid symptoms such as post-traumatic stress disorder. This testing typically lasts 2 hours.
- MRI and functional MRI Patients will undergo an MRI that indicates where they receive stimulation by a marker placed on a cap that displays brightly on an MRI. At Lucas center or the Palo Alto VA and involves brain imaging that will be related to brain stimulation techniques either through facilitating image guidance or providing information that will be correlated to data collected during stimulation. Typically, a session lasts about 2.5 hours since there is setup time involved.
- Transcranial Electrical Stimulation (tES) and Therapy Transcranial electric stimulation (tES) is a brain stimulation technique in which two electrodes will be placed on the participant's scalp and a weak, painless electrical current will be passed between the electrodes. These sessions will occur daily and last about 30 minutes. This protocol also integrates neuromodulation with stress management since combined stimulation and therapy have been demonstrated to be more effective. During tES, participants will practice meditation/relaxation/self-quieting using biofeedback (e.g. hand temperature monitoring). Participants will also receive weekly stress-management skills training. For participants with COVID-19 related stress, we will include specialized examples from a COVID-19 specialized therapy. During the meditation/relaxation/self-quieting, the participant will be asked to listen to a scripted recording or, in the event they do not like the recording or do not find it relaxing, they may negotiate an alternative with the study team (e.g. 30 minutes of classical music).
- Actigraphy Participants undergoing tES would be required to wear a watch-like device for 6 weeks during tES therapy that functions much like a "Fitbit" to measure their sleep and activity.
- Conditions
- Depression, Depressive Disorder, Treatment-Resistant, COVID Stress, PTSD - Post Traumatic Stress Disorder
- Being tested
- Psychological / Functional Assessment, Structural and Functional MRI, Transcranial Magnetic Brain Stimulation and MR Image Guidance, Transcranial Electrical Stimulation (tES)
- 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
- Medical subject headings
- Depression, Depressive Disorder, Treatment-Resistant, Combat Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Psychological / Functional AssessmentBehavioural
Psychological and functional assessment battery to characterize participants.
Structural and Functional MRIOther
Structural and functional magnetic resonance imaging session.
Transcranial Magnetic Brain Stimulation and MR Image GuidanceDevice
MRI guided transcranial magnetic stimulation and measurement of targeting accuracy.
Transcranial Electrical Stimulation (tES)Device
Home-based Transcranial Direct Current Stimulation
| Study group | Role | What they receive |
|---|---|---|
| Treatment Resistant Major Depression | Patients with treatment resistant major depression Receives: 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 Receives: Behavioral: Psychological / Functional Assessment; Other: Structural and Functional MRI; Device: Transcranial Electrical Stimulation (tES) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: [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).
Measured: [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
The WHODAS is an assessment of global functioning (range from 0 to 100 [0 = no disability, 100 = full disability]). The distance derived from the primary outcome analyses to look at precision will be applied as a continuous variable to correlate with change in the outcome measure from pre to post rTMS therapy targeted clinically with the Beam F3.
Measured: 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
The VR-36 is an 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). The distance derived from the primary outcome analyses to look at precision will be applied as a continuous variable to correlate with change in the outcome measure from pre to post rTMS therapy targeted clinically with the Beam F3.
Measured: 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
The HAMD-17 is a clinician-administered depression symptom assessment scale. Total score ranges from 0 (no depressive symptoms) to 52 (severe depressive symptoms). The distance derived from the primary outcome analyses to look at precision will be applied as a continuous variable to correlate with change in the outcome measure from pre to post rTMS therapy targeted clinically with the Beam F3.
Measured: Within one week before beginning clinical rTMS therapy and within one week after rTMS therapy termination.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2019
- Study start30 Sep 2019
- Primary completion31 Jul 2024
- Study completion31 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- Providence VA Medical Center, Atlanta VA Medical Center
- Responsible party
- Sponsor
- Investigators
- Allyson C Rosen, PhD, Principal investigator, VA Palo Alto Health Care System, Palo Alto, CA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03851380
- Sponsor's protocol ID
- D3152-R
- Other IDs
- 48212
- Acronym
- IBSI
- Status last verified
- Jul 2026
- First submitted
- 20 Feb 2019
- Last updated
- 3 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: We are sharing with collaborating institutions.
Publications
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.
PubMed 26115776Brown 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.
PubMed 20932915Cash 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.
PubMed 32800379
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Functional Improvement in rTMS Therapy
- ClinicalTrials.gov ID
- NCT03851380
- Acronym / sponsor ID
- IBSI / D3152-R
- Conditions
- Depression, Depressive Disorder, Treatment-Resistant, COVID Stress, PTSD - Post Traumatic Stress Disorder
- Keywords
- Transcranial Magnetic Stimulation, Magnetic Resonance Imaging, Functional Magnetic Resonance Imaging, fMRI, TMS, Neuronavigation, MRI, Transcranial Electrical Stimulation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- Providence VA Medical Center, Atlanta VA Medical Center
- Study start
- 30 Sep 2019 (actual)
- Primary completion
- 31 Jul 2024 (actual)
- Study completion
- 31 Jul 2024 (actual)
- First posted
- 22 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Potential participants are first identified and contact is made. Potential participants are then screened for inclusionary and exclusionary information (see tab 9. Eligibility) that relate to whether they can safely and comfortably perform the procedures and whether they are considered healthy or have the disorder for which brain stimulation therapy will be delivered. They will undergo informed consent that will disclose all the different risks and benefits for the procedures they will undergo. The list of procedures in which participants consent to participate is below. Participants may do either or both of the activities detailed below.
PROCEDURES:
For participants in the MRI and TMS targeting activity:
- Psychological / functional assessments: Interview, computerized, and paper and pencil measures of psychological functioning. These measures are used to characterize patients' diagnosis and psychological status. For example, depressed patients will answer questions about depressive symptoms and potentially comorbid symptoms such as post-traumatic stress disorder. This testing typically lasts 2 hours.
- MRI and functional MRI Patients will undergo an MRI that indicates where they receive stimulation by a marker placed on a cap that displays brightly on an MRI. MRI will occur at Lucas center or the Palo Alto VA and involves brain imaging that will be related to brain stimulation techniques either through facilitating image guidance or providing information that will be correlated to data collected during stimulation. Typically, a session lasts about 2.5 hours since there is setup time involved.
- Brain Stimulation:
TMS-transcranial magnetic stimulation which will be collected at the Palo Alto VA. Part of this procedure may include electromyography (EMG) which involves placing electrodes on the skin, typically the hand, and measuring indicators of muscle contraction. Sometimes this information is used to decide stimulation intensity during TMS and sometimes the TMS induced response will be a source of data in itself. Typically, this is only a measure conducted in parallel with other procedures and thus will not be given its own consent. MRI Guided TMS. An MRI will be used to target a selective brain region. To accomplish this, the MRI will be displayed on a computer screen and an infrared camera enables identification of the correspondence between the image and the participant's head. To study errors in scalp-based targeting, the investigators will perform scalp targeting while under MRI guidance but without the typical visual feedback provided by the MRI. Then this will be compared to scalp targeting with MRI guidance. The difference will identify typical errors in scalp targeting. Typically, a session will last approximately 1.5 hours.
For participants in the home-based neuromodulation and focused psychotherapy program:
- Psychological / functional assessments: Interview, computerized, and paper and pencil measures of psychological functioning. These measures are used to characterize patients' diagnosis and psychological status. For example, depressed patients will answer questions about depressive symptoms and potentially comorbid symptoms such as post-traumatic stress disorder. This testing typically lasts 2 hours.
- MRI and functional MRI Patients will undergo an MRI that indicates where they receive stimulation by a marker placed on a cap that displays brightly on an MRI. At Lucas center or the Palo Alto VA and involves brain imaging that will be related to brain stimulation techniques either through facilitating image guidance or providing information that will be correlated to data collected during stimulation. Typically, a session lasts about 2.5 hours since there is setup time involved.
- Transcranial Electrical Stimulation (tES) and Therapy Transcranial electric stimulation (tES) is a brain stimulation technique in which two electrodes will be placed on the participant's scalp and a weak, painless electrical current will be passed between the electrodes. These sessions will occur daily and last about 30 minutes. This protocol also integrates neuromodulation with stress management since combined stimulation and therapy have been demonstrated to be more effective. During tES, participants will practice meditation/relaxation/self-quieting using biofeedback (e.g. hand temperature monitoring). Participants will also receive weekly stress-management skills training. For participants with COVID-19 related stress, we will include specialized examples from a COVID-19 specialized therapy. During the meditation/relaxation/self-quieting, the participant will be asked to listen to a scripted recording or, in the event they do not like the recording or do not find it relaxing, they may negotiate an alternative with the study team (e.g. 30 minutes of classical music).
- Actigraphy Participants undergoing tES would be required to wear a watch-like device for 6 weeks during tES therapy that functions much like a "Fitbit" to measure their sleep and activity.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Resistant Major Depression | – | Behavioral: Psychological / Functional Assessment, Other: Structural and Functional MRI, Device: Transcranial Magnetic Brain Stimulation and MR Image GuidancePatients with treatment resistant major depression |
| COVID Stress | – | Behavioral: Psychological / Functional Assessment, Other: Structural and Functional MRI, Device: Transcranial Electrical Stimulation (tES)Veterans with COVID-19-related distress |
Who may qualify
- Ages
- 18 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Veteran patients with depression or COVID-19-related distress
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (32 listed)
- 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
- MRI exclusions include having any non-removable device or implant that makes scanning unsafe, claustrophobia, and size (e.g. weight, girth) beyond the constraints of the MRI and scanner bed
- For TMS the investigators will follow safety guidelines set by Rossi et. al.,2009
- Pregnant or planning to become pregnant within the next 3 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Psychological / Functional AssessmentPsychological and functional assessment battery to characterize participants. | Behavioural | COVID Stress, Treatment Resistant Major Depression |
| Structural and Functional MRIStructural and functional magnetic resonance imaging session. | Other | COVID Stress, Treatment Resistant Major Depression |
| Transcranial Magnetic Brain Stimulation and MR Image GuidanceMRI guided transcranial magnetic stimulation and measurement of targeting accuracy. | Device | Treatment Resistant Major Depression |
| Transcranial Electrical Stimulation (tES)Home-based Transcranial Direct Current Stimulation | Device | COVID Stress |
Primary outcome
Acceptable distance between TMS treatment location and brain target: Anticorrelation with Subgenual Cingulate
Time frame: [Within a week of clinical measures]
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)
Acceptable distance between TMS treatment location and brain target: fMRI Emotional Working Memory
Time frame: [Within a week of clinical measures]
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).
3 secondary outcomes
Correlation between change in World Health Organization Disability Assessment Schedule 2.0 (WHODAS) and distance from optimal TMS brain targets
Time frame: 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
Time frame: 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
Time frame: Within one week before beginning clinical rTMS therapy and within one week after rTMS therapy termination.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2026.
- Background: PubMed 26115776Mir-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.
- Background: PubMed 20932915Brown 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.
- Background: PubMed 32800379Cash 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.
- Individual participant dataSharing planned: No. We are sharing with collaborating institutions.
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Recruiting
Focused Ultrasound for Behavioral Health
Depression, Anxiety
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Allyson C Rosen, PhD principal investigator
VA Palo Alto Health Care System, Palo Alto, CA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Depression and Depressive Disorder, Treatment-Resistant, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acceptable distance between TMS treatment location and brain target: Anticorrelation with Subgenual Cingulate (time frame: [Within a week of clinical measures]). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03851380, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2026.