Open Label - Personalized Therapeutic Neuromodulation for Anhedonic Depression

NCT06052137 | Active Not Recruiting FDA Device

• 1 other identifier: 71771
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate the anti-anhedonic efficacy of a novel neurostimulation strategy termed accelerated intermittent theta burst stimulation (aiTBS) in participants with treatment resistant depression (TRD).

Conditions

Treatment Resistant Depression

Keywords

transcranial magnetic stimulation; theta burst

Outcome Measures

Primary Outcomes (1)

• Change in clinician-administered MADRS from Baseline to Week 1 post-treatment-initiation

  The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item clinician-administered scale, designed to be particularly sensitive to antidepressant treatment effects in patients with major depression. Score range of 0-60. A higher score is indicative of more depression.

  Baseline, 1-week post-treatment-initiation

Study Arms (2)

Active TBS-DLPFC

ACTIVE COMPARATOR

The active group will receive theta-burst TMS DLPFC stimulation.

Device: Active TBS-DLPFC

Active TBS-DMPFC

ACTIVE COMPARATOR

The active group will receive theta-burst TMS DMPFC stimulation.

Device: TBS-DMPFC

Interventions

Active TBS-DLPFC DEVICE

Participants will receive intermittent TBS to left DLPFC. The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of RMT and adjusted to the skull to cortical surface distance (see Nahas 2004). Stimulation will be delivered to the L-DLPFC using a MagPro TMS system (MagVenture, Denmark).

Active TBS-DLPFC

TBS-DMPFC DEVICE

Participants will receive intermittent TBS to DMPFC. The DMPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of RMT and adjusted to the skull to cortical surface distance (see Nahas 2004). Stimulation will be delivered to the DMPFC using a MagPro TMS system (MagVenture, Denmark).

Active TBS-DMPFC

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or Female, between the ages of 18 and 80 at the time of screening.
• Able to read, understand, and provide written, dated informed consent prior to screening. Proficiency in English sufficient to complete questionnaires / follow instructions during fMRI assessments and aiTBS interventions. Stated willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information.
• Currently diagnosed with Major Depressive Disorder (MDD) and meets criteria for a Major Depressive Episode, according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5).
• MADRS score of ≥20 at screening (Visit 1).
• TMS naive for one of the following areas: DLPCF or DMPFC
• The dose of the primary antidepressant medication (if applicable) must be stable for 6 weeks prior to baseline, and participant must agree to continue at this dose throughout the study period.
• In good general health, as evidenced by medical history.
• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation.
• Agreement to adhere to Lifestyle Considerations throughout study duration.
• Lifestyle Considerations:
• Abstain from becoming pregnant from the screening visit (Visit 1) until after the final study visit (Visit 10).
• Abstain from caffeine- or xanthine-containing products (e.g., coffee, tea, cola drinks, and chocolate) for 3 hours before the start of each dosing session until after the final TMS session.
• Abstain from alcohol for 24 hours before the start of each dosing session until after collection of the final MRI.
• Participants who use tobacco products will be instructed that use of cigarettes will not be allowed during the study.

You may not qualify if:

• Pregnancy
• History of or current psychotic disorder or bipolar disorder
• Severe borderline personality disorder.
• Diagnosis of Intellectual Disability or Autism Spectrum Disorder
• Primary psychiatric condition other than MDD requiring treatment except stable comorbid anxiety disorder
• Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal
• Urine screening test positive for illicit substances
• Acute suicide risk based on clinical judgement or a suicide attempt (as defined by the C-SSRS) within the past one year
• Any history of ECT (greater than 8 sessions) without meeting responder criteria
• Recent (within 4 weeks of any clinical effect) or concurrent use of rapid acting antidepressant agent (i.e., ketamine or a course of ECT)
• History of significant neurologic disease, including dementia, Parkinson's or Huntington's disease, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma
• Untreated or insufficiently treated endocrine disorder.
• Contraindication to receiving rTMS (e.g., metal in head, history of seizure, known brain lesion)
• Contraindication to MRI (ferromagnetic metal in their body)
• Treatment with an investigational drug or other intervention within the study period

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• David Spiegel, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Psychiatry and Behavioral Sciences, Stanford School of Medicine

Study Record Dates

• First Submitted: September 18, 2023
• First Posted: September 25, 2023
• Study Start: December 19, 2023
• Primary Completion: October 1, 2025
• Study Completion: October 1, 2025
• Last Updated: April 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)