Mindfulness Engaged Neurostimulation for Depression

NCT ID: NCT06399406

Last Updated: 2025-08-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-15
• Study Completion Date: 2026-04-30

Brief 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%. 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. The study will determine the optimal dose required for 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Medi-TBS

Intervention Type: COMBINATION_PRODUCT

The multimodal intervention involves combining FDA-approved repetitive transcranial magnetic stimulation (rTMS) with digital mindfulness exercises.

Medi2-TBS

This arm will receive a multimodal treatment with a digital mindfulness training focused on attention to breathing for up to 20 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.

Group Type: EXPERIMENTAL

Medi-TBS

Intervention Type: COMBINATION_PRODUCT

The multimodal intervention involves combining FDA-approved repetitive transcranial magnetic stimulation (rTMS) with digital mindfulness exercises.

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.

Group Type: ACTIVE_COMPARATOR

Medi-TBS

Intervention Type: COMBINATION_PRODUCT

The multimodal intervention involves combining FDA-approved repetitive transcranial magnetic stimulation (rTMS) with digital mindfulness exercises.

Interventions

Medi-TBS

The multimodal intervention involves combining FDA-approved repetitive transcranial magnetic stimulation (rTMS) with digital mindfulness exercises.

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

Jyoti Mishra

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jyoti Mishra, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Locations

University of California San Diego

La Jolla, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jyoti Mishra, PhD

Role: CONTACT

braine@ucsd.edu

8582322855

Facility Contacts

Jyoti Mishra, PhD

Role: primary

braine@ucsd.edu

858-232-2855

Dhakshin Ramanathan, MD PhD

Role: backup

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

809712

Identifier Type: -

Identifier Source: org_study_id