Sham-Controlled Rapid-Acting Neuromodulation for Depression

The goal of this study is to learn whether 5 days of accelerated intermittent theta burst stimulation (iTBS), a rapid form of transcranial magnetic stimulation (TMS), which is a non-invasive procedure that uses magnetic fields to stimulate brain activity, works to treat depression in adults.

The main questions it aims to answer are:

• Does accelerated iTBS reduce depressive symptoms compared to sham (placebo) stimulation?
• Are there measurable brain, biological, and digitally measured emotion changes associated with treatment response?

Participants will:

• Be randomly assigned to receive either active iTBS or sham stimulation
• Receive 10 stimulation sessions per day for 5 consecutive days (total of 50 sessions)
• Complete MRI brain scans and EEG recordings before and after treatment
• Provide blood and saliva samples to measure biological markers
• Complete depression rating scales and questionnaires at baseline, during treatment, and at follow-up visits
• Use a secure mobile app to record brief facial and vocal samples during the 5-day treatment and at follow-up visits
• Return for follow-up visits at 1 week and at 1, 3, 6, and 12 months after treatment

Study Overview

• Status: Not yet recruiting
• Conditions: Depression - Major Depressive Disorder
• Intervention / Treatment: Device: intermittent theta burst stimulation; Device: Sham (No Treatment)

• Study Type: Interventional
• Enrollment (Estimated): 264
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Manpreet K Singh, MD, MS; Phone Number: 916-734-2011; Email: mpksingh@health.ucdavis.edu

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
      • Contact: Manpreet K Singh, MD, MS; Phone Number: 916-734-2011; Email: mpksingh@health.ucdavis.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• English speaking
• Able to provide informed consent
• 18-65 years old
• Meets MDD criteria per the Mini International Neuropsychiatric Interview (MINI)

Exclusion Criteria:

• Unable to consent (due to medical condition, acute psychosis, substance use, etc)
• Use of benzodiazepines or medications that would interfere with TMS treatment as per PI discretion
• Active substance use or severe substance use that in the opinion of the PI would interfere with study participation
• Untreated, active psychosis
• Female patient who is breastfeeding, pregnant or who is planning a pregnancy during the study
• Contraindications to receiving TMS and/or MRI as determined by screening questionnaires
• Participation in any clinical study with exposure to any investigational treatment or product within the previous 30 days, or plan on concurrent participation in other studies.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active iTBS; The active iTBS group will receive 10 hourly intermittent theta burst stimulation (iTBS) sessions per day for 5 consecutive days.	Device: intermittent theta burst stimulation; The TMS protocol involves delivering sessions of intermittent theta burst stimulation (iTBS) of 60 cycles of 10 bursts of three pulses at 50 Hz delivered in 2-second trains (5 Hz) with an 8-second intertrain interval. Stimulation sessions will be delivered hourly. Ten sessions will be applied per day (18,000 pulses/day) for 5 consecutive days (90,000 pulses in total). Stimulation will be delivered at 90% resting motor threshold (rMT). For safety, stimulation will never be delivered above 120% rMT. Participants assigned to the sham group will receive treatment using a sham TMS coil.
Sham Comparator: Sham iTBS; Participants assigned to the sham group will receive 10 hourly sham sessions per day for 5 consecutive days.	Device: Sham (No Treatment); Participants assigned to the sham group will receive treatment using a sham TMS coil. This coil looks and sounds similar to the active coil but does not deliver magnetic pulses to the brain.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery-Åsberg Depression Rating Scale (MADRS)	Change in depressive symptoms (MADRS scores)	Baseline through study completion, 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in large-scale brain network connectivity measured by fMRI	Change in resting-state functional connectivity within and between large-scale brain networks associated with depression, including the default mode network, salience network, and central executive network.	Baseline through study completion, 1 year
Change in electroencephalography (EEG) spectral power	Change in resting-state electroencephalography (EEG) spectral power across frequency bands (delta, theta, alpha, beta, and gamma).	Baseline through study completion, 1 year
Change in facial and vocal affective expression	Change in multimodal affective dynamics derived from combined facial and vocal recordings using machine learning-based analysis to generate composite measures of emotional expression and variability.	Baseline through study completion, 1 year

Collaborators and Investigators

• Sponsor: University of California, Davis

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: March 9, 2026
• First Submitted That Met QC Criteria: March 17, 2026
• First Posted (Actual): March 23, 2026

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: 2398605-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: De-identified individual participant data (IPD) of the results reported in publications may be made available upon reasonable request. Requests will be reviewed by the Principal Investigator to ensure that the proposed use is scientifically appropriate and consistent with participant consent and institutional policies.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes