DepressionPhase 2NCT07512284
Mindfulness Engaged Neurostimulation for Depression (MEND II)
A Phase 2 study testing Medi-TBS in people with Depression and Treatment Resistant Depression, run by University of California, San Diego at 1 site in United States.
Trial summary
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%. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Depression, Treatment Resistant Depression, Major Depressive Disorder
- What is being tested?
- Medi-TBS
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2026to 30 Apr 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
UC San Diego Health Psychiatry
San Diego, California, 92037
Jyoti Mishra, PhD, 8582322855, braine@ucsd.edu
About this study
Official title: 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.
Read the 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.
- Conditions
- Depression, Treatment Resistant Depression, Major Depressive Disorder, Depressive Disorder, Depressive Symptoms
- Being tested
- Medi-TBS
- Medical subject headings
- Depression, Depressive Disorder, Treatment-Resistant, Depressive Disorder, Major, Depressive Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Medi-TBSCombination product
The multimodal intervention involves combining FDA-approved repetitive transcranial magnetic stimulation (rTMS) with digital mindfulness exercises.
| Study group | Role | What they receive |
|---|---|---|
| Medi1-TBS | Experimental | 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. Receives: Combination Product: Medi-TBS |
| Medi3-TBS | Active comparator | 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. Receives: Combination Product: Medi-TBS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in EEG source localized pDMN alpha activity
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.
Measured: 4 weeks
Secondary outcomes (3)
Change in Selective Attention
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.
Measured: 4 weeks
Change in Flanker Inhibition
Efficiency of inhibiting visuo-spatially flanking distractors to target stimuli in the Flanker task serves as the secondary cognitive target.
Measured: 4 weeks
Change in Montgomery Åsberg Depression Rating Scale Scores (MADRS)
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.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2026
- Study start1 May 2026 (estimated)
- Primary completion30 Apr 2029 (estimated)
- Study completion30 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DepressionStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jyoti Mishra, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07512284
- Sponsor's protocol ID
- MEND II
- Status last verified
- May 2026
- First submitted
- 30 Mar 2026
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mindfulness Engaged Neurostimulation for Depression
- ClinicalTrials.gov ID
- NCT07512284
- Acronym / sponsor ID
- MEND II
- Conditions
- Depression, Treatment Resistant Depression, Major Depressive Disorder, Depressive Disorder, Depressive Symptoms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Study start
- 1 May 2026 (estimated)
- Primary completion
- 30 Apr 2029 (estimated)
- Study completion
- 30 Apr 2029 (estimated)
- First posted
- 6 Apr 2026 (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.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Medi1-TBS | Experimental | Combination Product: Medi-TBSThis 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. |
| Medi3-TBS | Active comparator | Combination Product: Medi-TBSThis 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
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 |
|---|---|---|
| Medi-TBSThe multimodal intervention involves combining FDA-approved repetitive transcranial magnetic stimulation (rTMS) with digital mindfulness exercises. | Combination product | Medi1-TBS, Medi3-TBS |
Primary outcome
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.
3 secondary outcomes
Change in Selective Attention
Time frame: 4 weeks
Change in Flanker Inhibition
Time frame: 4 weeks
Change in Montgomery Åsberg Depression Rating Scale Scores (MADRS)
Time frame: 8 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
- Individual participant dataSharing planned: Yes. 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.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Medi-TBS in people with Depression and Treatment Resistant Depression, run by University of California, San Diego 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 5 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 6 May 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jyoti Mishra, PhD (858-232-2855, braine@ucsd.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in EEG source localized pDMN alpha activity (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 May 2026.