Establishing a Dose-response Relationship With Accelerated Transcranial Magnetic Stimulation

May 5, 2022 updated by: David Spiegel, Stanford University

Utilizing Changes in Human Brain Connectivity to Establish a Dose-response Relationship Involved in the Therapeutic Actions of Prefrontal Brain Stimulation on Depression Symptoms

This study evaluates an accelerated schedule of theta-burst stimulation using a transcranial magnetic stimulation device for treatment-resistant depression. In a double-blind, randomized, sham-controlled fashion, half the participants will receive accelerated theta-burst stimulation while half will receive sham treatment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Repetitive transcranial magnetic stimulation (rTMS) is an established therapy for treatment-resistant depression. The approved method for treatment is 10Hz stimulation for 40 min over the left dorsolateral prefrontal cortex (L-DLPFC). This methodology has been effective in real world situations. The limitations of this approach include the duration of the treatment (approximately 40 minutes per treatment session, 5 days per week, for 4-8 weeks). Recently, we have pursued modifying the treatment parameters to reduce treatment times with an accelerated treatment paradigm with great preliminary success. This study aims to further study our accelerated protocol and examine changes in neuroimaging biomarkers.

Dr. Nolan Williams is the Principle Investigator on the grant associated for this study and so is listed as Study Director on the study record.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Not Applicable

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 Locations

  • United States
    • California
      • Stanford, California, United States, 94305
        • Recruiting
        • Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine
        • 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

Ages Eligible for Study

22 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or Female, between the ages of 22 and 65 at the time of screening.
  2. 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.
  3. 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).
  4. Medical records confirming a history of moderate to severe treatment-resistance as defined by a score of 7-14 on the Maudsley Staging Method (MSM3).
  5. MADRS score of ≥20 at screening (Visit 1).
  6. TMS naive.
  7. Access to ongoing psychiatric care before and after completion of the study.
  8. Access to clinical rTMS after study completion.
  9. Must be on a stable antidepressant therapeutic regimen for 6 weeks prior to study enrollment and agree to continue this regimen throughout the study period.
  10. In good general health, as evidenced by medical history.
  11. 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.
  12. Agreement to adhere to Lifestyle Considerations throughout study duration.

Lifestyle considerations:

  1. Abstain from becoming pregnant from the screening visit (Visit 1) until after the final study visit (Visit 9).
  2. Continue usual intake patterns of caffeine- or xanthine-containing products (e.g., coffee, tea, cola drinks, and chocolate) without significant change for the duration of the study.
  3. Abstain from alcohol for at least 24 hours before the start of each MRI and TMS session. Participants who use tobacco products will be informed that use will be allowed only in between intervention sessions.

Exclusion Criteria:

  1. Pregnancy
  2. Primary psychiatric condition other than MDD requiring treatment except stable comorbid anxiety disorder
  3. History of or current psychotic disorder or bipolar disorder
  4. Severe borderline personality disorder.
  5. Diagnosis of Intellectual Disability or Autism Spectrum Disorder
  6. Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal
  7. Urine screening test positive for illicit substances
  8. Active suicidal ideation (defined as an MSSI > 8) or a suicide attempt (as defined by the C-SSRS) within the past one year
  9. Any history of ECT (greater than 8 sessions) without meeting responder criteria
  10. Recent (within 4 weeks of any clinical effect) or concurrent use of rapid acting antidepressant agent (i.e., ketamine or a course of ECT)
  11. 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
  12. Untreated or insufficiently treated endocrine disorder.
  13. Contraindication to receiving rTMS (e.g., metal in head, history of seizure, known brain lesion)
  14. Contraindication to MRI (ferromagnetic metal in their body)
  15. Treatment with another investigational drug or other intervention within the study period
  16. Depth-adjusted aiTBS treatment dose > 65% maximum stimulator output (MSO)
  17. Unstable symptoms between screening and baseline as defined by a ≥ 30% change in MADRS-S score.
  18. Any other condition deemed by the PD to interfere with the study or increase risk to the participant

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: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Active TBS-DLPFC
The active group will receive theta-burst TMS stimulation.
Device: Active TBS-DLPFC

Participants in the active stimulation group 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 x100 TMS system (MagVenture, Denmark).
Sham Comparator: Sham TBS-DLPFC
The sham group will receive sham theta-burst TMS stimulation.
Device: Sham TBS-DLPFC
The parameters in the sham arm will be as above with the internal randomization of the device internally switching to sham in a blinded fashion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in resting state functional connectivity of the subgenual anterior cingulate cortex (sgACC) and the default mode network (DMN).
Time Frame: At baseline (day 3) and at immediate post-treatment follow up visit (day 8).
Assessment of functional connectivity of sgACC to the DMN using magnetic resonance imaging.
At baseline (day 3) and at immediate post-treatment follow up visit (day 8).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relationship between clinical improvement and resting state functional connectivity between the sgACC and DMN in active vs. sham participants.
Time Frame: At baseline (day 3) and at immediate post-treatment follow up visit (day 8).

Assessment of clinical improvement by the Montgomery Asberg Depression Rating Scale-self report (MADRS-S).

The 9-item self-report version of the MADRS has an overall score range from 0-27, with higher scores corresponding to higher levels of depression.

Assessment of functional connectivity of sgACC to the DMN using magnetic resonance imaging.
At baseline (day 3) and at immediate post-treatment follow up visit (day 8).
Relationship between acute mood state and resting state functional connectivity between the sgACC and DMN in active vs. sham participants.
Time Frame: At baseline (day 3) and at immediate post-treatment follow up visit (day 8).
Assessment of acute mood state by the Immediate Mood Scaler-12 item (IMS-12). Assessment of functional connectivity of sgACC to the DMN using magnetic resonance imaging.
At baseline (day 3) and at immediate post-treatment follow up visit (day 8).

Collaborators and Investigators

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

Sponsor

Stanford University

Investigators

  • Study Director: Nolan Williams, MD, Stanford University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

June 15, 2021

Primary Completion (Anticipated)

December 1, 2025

Study Completion (Anticipated)

December 1, 2026

Study Registration Dates

First Submitted

January 25, 2020

First Submitted That Met QC Criteria

January 27, 2020

First Posted (Actual)

January 28, 2020

Study Record Updates

Last Update Posted (Actual)

May 6, 2022

Last Update Submitted That Met QC Criteria

May 5, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 54909

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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.

Clinical Trials on Treatment Resistant Depression

Clinical Trials on Sham TBS-DLPFC

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kyrgyzstan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe