Mindfulness Engaged Neurostimulation for Depression (MEND II) (MEND II)

May 1, 2026 updated by: Jyoti Mishra, University of California, San Diego

Mindfulness Engaged Neurostimulation for Depression

Repetitive Transcranial Magnetic stimulation (rTMS) is an FDA-approved therapy for treatment resistant depression (TRD) that involves brief magnetic stimulation pulses on the dorsolateral prefrontal cortex (DLPFC) brain region. But studies of rTMS alone show remission rates of ~30%. Additionally, rTMS has not been shown to improve cognitive functioning that may be an independent factor predicting treatment success. This study will develop a novel multimodal treatment, which combines intermittent theta burst stimulation (iTBS) - a type of rTMS with digital mindfulness training to engage brain plasticity, enhance cognition and alleviate depression symptoms in individuals with TRD.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study aims to develop a novel multimodal treatment for treatment resistant depression (TRD), which combines intermittent theta burst stimulation (iTBS), a type of FDA-approved rTMS protocol, with digital mindfulness training. We propose that this multimodal treatment will suppress posterior Default Mode Network (pDMN) brain activity as measured with electroencephalography (primary outcome and neural target), as well as enhance cognition and alleviate depression symptoms in patients with TRD (secondary outcomes). The study will conduct a two-arm randomized controlled trial to demonstrate neural target engagement by the multimodal iTBS + digital mindfulness training relative to an active control training combined with iTBS.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
120

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Jyoti Mishra, PhD
  • Phone Number: 858-232-2855
  • Email: braine@ucsd.edu

Study Locations

  • United States
    • California
      • San Diego, California, United States, 92037
        • Recruiting
        • UC San Diego Health Psychiatry
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of major depressive episode (MDE, in accordance with the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5), in the context of unipolar major depressive disorder.
  • At least one failed antidepressant medication trial at level 3 in the Antidepressant -Treatment History Form: Short Form (ATHF-SF) classification.
  • Montgomery-Åsberg Depression Rating Scale (MADRS) Score >19 (moderate - severe depression).
  • No increase or initiation of new antidepressant therapy in the four weeks prior to screening.
  • Demonstrated capacity to give informed consent.

Exclusion Criteria:

  • Inability to provide informed consent.
  • Medically unstable patients.
  • Concomitant neurological disorder or a history of a seizure disorder.
  • Exhibiting current suicidal behavior rating on the Columbia Suicide Severity Rating Scale (C-SSRS)
  • Patients who are pregnant or breastfeeding.
  • Any psychotic disorder or current active psychotic symptoms.
  • Patients who have intracranial implants, other medical device or condition deemed unsafe for TMS.
  • Contraindication to MRI scanning.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Medi1-TBS
This arm will receive a multimodal treatment with a digital mindfulness training focused on attention to breathing for up to 10 min session dose for up to 20 sessions combined with neuro-navigated iTBS type of rTMS (for 20 treatments over 4 weeks) targeting the left dorsolateral prefrontal cortex (DLPFC) brain region.
Combination product: Medi-TBS
The multimodal intervention involves combining FDA-approved repetitive transcranial magnetic stimulation (rTMS) with digital mindfulness exercises.
Active Comparator: Medi3-TBS
This arm will receive a multimodal treatment with a digital mindfulness training focused on intermittent deep breathing for up to 10 min session dose for up to 20 sessions combined with neuro-navigated iTBS type of rTMS (for 20 treatments over 4 weeks) targeting the left dorsolateral prefrontal cortex (DLPFC) brain region.
Combination product: Medi-TBS
The multimodal intervention involves combining FDA-approved repetitive transcranial magnetic stimulation (rTMS) with digital mindfulness exercises.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in EEG source localized pDMN alpha activity
Time Frame: 4 weeks
EEG alpha band (8-12 Hz) activity source-localized to the posterior Default Mode Network (pDMN) brain region extracted on distracted trials of the Breath Attention Assessment of Mindfulness task serves as the primary neural target.
4 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Selective Attention
Time Frame: 4 weeks
Processing speed of response to target stimuli on a standard continuous performance task that measures the ability to selectively attend and promptly respond to a goal-relevant target stimulus serves as the secondary cognitive target.
4 weeks
Change in Flanker Inhibition
Time Frame: 4 weeks
Efficiency of inhibiting visuo-spatially flanking distractors to target stimuli in the Flanker task serves as the secondary cognitive target.
4 weeks
Change in Montgomery Åsberg Depression Rating Scale Scores (MADRS)
Time Frame: 8 weeks
The MADRS will be used to evaluate % depressive symptom response defined as 50% change in the MADRS score from baseline as well as remission defined as MADRS score <7 at post-intervention. Scale range: 0-54, higher score is worse depression.
8 weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Working Memory
Time Frame: 4 weeks
Span-weighted efficiency will be measured on a standard Delayed Match to Sample Task
4 weeks
Change in Mindful Attention Awareness Scale (MAAS)
Time Frame: 4 weeks
The MAAS will be used to evaluate change in subjective state mindfulness. Scale range: 6-84, higher score is greater mindfulness
4 weeks
Change in Rumination Reflection Questionnaire (RRQ)
Time Frame: 4 weeks
The RRQ will be used to evaluate change in subjective rumination. Scale range: 22-88, higher score is greater rumination
4 weeks
Change in Patient Health Questionnaire 9 item scale (PHQ9)
Time Frame: 8 weeks
The PHQ9 scale will be used as an additional measure to evaluate change in depressive symptom response. Score range: 0-27, higher score is greater depression
8 weeks
Change in Generalized Anxiety Disorder 7 item scale (GAD7)
Time Frame: 8 weeks
The GAD7 scale will be used as a measure to evaluate change in anxiety symptom response. Score range: 0-21, higher score is greater anxiety.
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of California, San Diego

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 30, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 30, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 30, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 6, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 6, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 1, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MEND II

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

In compliance with National Institute of Mental Health requirements for data sharing, collected data will be shared via the National Database for Clinical Trials related to Mental Illness (NDCT).

Data submissions will include raw and processed data including basic demographic data, cognitive, behavioral, clinical data, and electroencephalography (EEG) data. All data will be structured as per a Data Dictionary that will be used for data harmonization purposes; data structure definitions will be taken from the existing NIMH Data Archive (NDA) Data Dictionary as recommended, however, if any data are not defined in the existing NDA Data Dictionary, then a new definition will be requested.

IPD Sharing Time Frame

We will submit raw/descriptive data semi-annually (every January and July) and submit all other data at the time of publication of the initial report from the project.

IPD Sharing Access Criteria

Access to study data will be available via the NDCT.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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