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Establishing a Dose-response Relationship With Accelerated Transcranial Magnetic Stimulation

Primary Purpose

Treatment Resistant Depression

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Active TBS-DLPFC
Sham TBS-DLPFC
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Treatment Resistant Depression focused on measuring transcranial magnetic stimulation, theta burst

Eligibility Criteria

22 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Department of Psychiatry and Behavioral Sciences, Stanford School of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Active TBS-DLPFC

Sham TBS-DLPFC

Arm Description

The active group will receive theta-burst TMS stimulation.

The sham group will receive sham theta-burst TMS stimulation.

Outcomes

Primary Outcome Measures

Change in resting state functional connectivity of the subgenual anterior cingulate cortex (sgACC) and the default mode network (DMN).
Assessment of functional connectivity of sgACC to the DMN using magnetic resonance imaging.

Secondary Outcome Measures

Relationship between clinical improvement and resting state functional connectivity between the sgACC and DMN in active vs. sham participants.
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.
Relationship between acute mood state and resting state functional connectivity between the sgACC and DMN in active vs. sham participants.
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.

Full Information

First Posted
January 25, 2020
Last Updated
May 5, 2022
Sponsor
Stanford University
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1. Study Identification

Unique Protocol Identification Number
NCT04243798
Brief Title
Establishing a Dose-response Relationship With Accelerated Transcranial Magnetic Stimulation
Official Title
Utilizing Changes in Human Brain Connectivity to Establish a Dose-response Relationship Involved in the Therapeutic Actions of Prefrontal Brain Stimulation on Depression Symptoms
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 15, 2021 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Treatment Resistant Depression
Keywords
transcranial magnetic stimulation, theta burst

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active TBS-DLPFC
Arm Type
Experimental
Arm Description
The active group will receive theta-burst TMS stimulation.
Arm Title
Sham TBS-DLPFC
Arm Type
Sham Comparator
Arm Description
The sham group will receive sham theta-burst TMS stimulation.
Intervention Type
Device
Intervention Name(s)
Active TBS-DLPFC
Intervention Description
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).
Intervention Type
Device
Intervention Name(s)
Sham TBS-DLPFC
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in resting state functional connectivity of the subgenual anterior cingulate cortex (sgACC) and the default mode network (DMN).
Description
Assessment of functional connectivity of sgACC to the DMN using magnetic resonance imaging.
Time Frame
At baseline (day 3) and at immediate post-treatment follow up visit (day 8).
Secondary Outcome Measure Information:
Title
Relationship between clinical improvement and resting state functional connectivity between the sgACC and DMN in active vs. sham participants.
Description
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.
Time Frame
At baseline (day 3) and at immediate post-treatment follow up visit (day 8).
Title
Relationship between acute mood state and resting state functional connectivity between the sgACC and DMN in active vs. sham participants.
Description
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.
Time Frame
At baseline (day 3) and at immediate post-treatment follow up visit (day 8).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
22 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or Female, between the ages of 22 and 65 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). 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). MADRS score of ≥20 at screening (Visit 1). TMS naive. Access to ongoing psychiatric care before and after completion of the study. Access to clinical rTMS after study completion. 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. 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 9). 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. 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: Pregnancy Primary psychiatric condition other than MDD requiring treatment except stable comorbid anxiety disorder History of or current psychotic disorder or bipolar disorder Severe borderline personality disorder. Diagnosis of Intellectual Disability or Autism Spectrum Disorder Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal Urine screening test positive for illicit substances Active suicidal ideation (defined as an MSSI > 8) 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 another investigational drug or other intervention within the study period Depth-adjusted aiTBS treatment dose > 65% maximum stimulator output (MSO) Unstable symptoms between screening and baseline as defined by a ≥ 30% change in MADRS-S score. Any other condition deemed by the PD to interfere with the study or increase risk to the participant
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nick Bassano, MSW
Phone
650-736-2233
Email
nbassano@stanford.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nolan Williams, MD
Organizational Affiliation
Stanford University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
David Spiegel, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nick Bassano, MSW
Phone
650-736-2233
Email
nbassano@stanford.edu

12. IPD Sharing Statement

Plan to Share IPD
No
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Establishing a Dose-response Relationship With Accelerated Transcranial Magnetic Stimulation

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